Sei sulla pagina 1di 1634

Surgery of the Breast

Principles and Art


Third Edition

Volume One

Surgery of the Breast


Principles and Art
Third Edition
Editor
SCOTT L. SPEAR,
MD, FACS
Professor and Chairman Department of Plastic Surgery Georgetown University Hospital Washington, DC

Associate Editors
SHAWNA C. WILLEY,
MD

DENNIS C. HAMMOND,

MD

Director, Betty Lou Ourisman Breast Health Center Associate Professor of Clinical Surgery Department of Surgery Georgetown University Medical Center Washington, DC

GEOFFREY L. ROBB,
Professor and Chair Department of Plastic Surgery The University of Texas M.D. Anderson Cancer Center Houston, Texas

MD

Clinical Assistant Professor Department of Surgery Michigan State University College of Human Medicine East Lansing, Michigan Associate Program Director Plastic and Reconstructive Surgery Grand Rapids Medical Education Partners Grand Rapids, Michigan

MAURICE Y. NAHABEDIAN,
Associate Professor Department of Plastic Surgery Georgetown University Hospital Washington, DC

MD

Acquisitions Editor: Brian Brown Managing Editor: Julia Seto Marketing Manager: Lisa Lawrence Production Editor: Alicia Jackson Senior Manufacturing Manager: Ben Rivera Designer: Doug Smock Compositor: Aptara, Inc. Copyright 2011 Lippincott Williams & Wilkins Two Commerce Square 2001 Market Street Philadelphia, PA 19103 All rights reserved. This book is protected by copyright. No part of this book may be reproduced in any form or by any means, including photocopying, or utilized by any information storage and retrieval system without written permission from the copyright owner. The publisher is not responsible (as a matter of product liability, negligence, or otherwise) for any injury resulting from any material contained herein. This publication contains information relating to general principles of medical care that should not be construed as specic instructions for individual patients. Manufacturers product information and package inserts should be reviewed for current information, including contraindications, dosages, and precautions. Printed in China Library of Congress Cataloging-in-Publication Data Surgery of the breast : principles and art / editor, Scott L. Spear ; associate editors, Shawna C. Willey . . . [et al.]. -- 3rd ed. p. ; cm. Includes bibliographical references and index. ISBN 978-1-60547-577-6 (hardback : alk. paper) 1. BreastCancerSurgery. 2. BreastSurgery. 3. Mammaplasty. 4. Mastectomy. I. Spear, Scott L. [DNLM: 1. Breastsurgery. 2. Breast Neoplasmssurgery. 3. Mammaplastymethods. 4. Mastectomymethods. WP 910] RD667.5.S87 2011 616.99449059dc22 2010034582 The publishers have made every effort to trace the copyright holders for borrowed material. If they have inadvertently overlooked any, they will be pleased to make the necessary arrangements at the rst opportunity. To purchase additional copies of this book, call our customer service department at (800) 638-3030 or fax orders to (301) 223-2320. International customers should call (301) 2232300. Visit Lippincott Williams & Wilkins on the Internet: http:/ /www.LWW.com. Lippincott Williams & Wilkins customer service representatives are available from 8:30 am to 6:00 pm, EST. 06 07 08 09 10 1 2 3 4 5 6 7 8 9 10

To my teachers and professors who served as role models and left their indelible marks on how I think and operate: Bob Replogle from the University of Chicago who directed me into a surgical career and helped me grow up as a medical student; Bill Silen and Don Glotzer, both general surgeons from the Beth Israel at Harvard who set the standard of integrity and discipline that I humbly try to emulate to this day; Ralph Millard from the University of Miami who singularly embodies artistic skill, creativity, hard work, and the never satised pursuit of beautiful outcomes; and also my colleagues around the country who toil at the same work as I do and inspire me to think smarter and work harder to raise the bar on what we can achieve. To the women who have allowed me to take care of them, repair them, or enhance them such that their lives have been made more pleasant, comfortable, or even pleasurable. Helping them has enriched my life at least as much as I have enriched theirs. To Cindy, my wife, who never ceases to amaze with her seemingly unlimited energy, sensitivity, thoughtfulness, compassion, generosity, wisdom, loyalty, and love that ows so easily from her and enriches the lives of everyone that she touches, including me, thankfully.

Contributing Authors

William P. Adams, Jr., MD


Associate Clinical Professor Department of Plastic Surgery UT Southwestern Medical Center Dallas, Texas

Louis C. Benelli, MD
Department of Surgery Bichat Hospital University of Paris Paris, France

Jamal Ahmad, MD
Staff Plastic Surgeon The Plastic Surgery Clinic Mississauga, Ontario, Canada

Bradley P. Bengtson, MD, FACS


Bengtson Center for Aesthetics and Plastic Surgery Department of Plastic Surgery Spectrum Health Grand Rapids, Michigan

Ali Al-Attar, MD
Department of Plastic Surgery Georgetown University Hospital Washington, DC

Thomas Biggs, MD
Clinical Professor of Plastic Surgery College of Medicine Baylor University Houston, Texas

Wafa Alkhayal, MD
Georgetown University Hospital Division of Breast Surgery Washington, DC

Jay Boehmler, MD
Assistant Professor Division of Plastic Surgery The Ohio State University Columbus, Ohio

Robert J. Allen, MD, FACS


Louisiana State University Health Sciences Center New Orleans, Louisiana

Mitchell H. Brown, MD Rebecca Cogwell Anderson, PhD


Professor Department of Surgery Medical College of Wisconsin Frodfert Memorial Lutheran Hospital Milwaukee, Wisconsin Associate Professor Department of Surgery Program Director Division of Plastic Surgery University of Toronto Toronto, Ontario, Canada

Matthew B. Baker, MD, PhD


Baker Center for Plastic Surgery Staff Surgeon Division of Plastic Surgery Littleton Adventist Hospital Littleton, Colorado

Klaus E. Brunnert, MD
Chief Department of Senology Klinik Fur Senologie Osnabruck, Germany

Edward P. Buchanan, MD Elisabeth K. Beahm, MD, FACS


The University of Texas M.D. Anderson Cancer Center Department of Plastic Surgery Houston, Texas Fellow in Plastic Surgery

Celia Byrne, MD
Cancer Genetics and Epidemiology Lombardi Cancer Center Georgetown University Hospital Washington, DC

Michael Beckenstein, MD
Birmingham, Alabama

Hilton Becker, MD, FACS, FRCS


Division of Plastic Surgery University of Miami Miller School of Medicine Boca Raton, Florida

Paul R. Callegari, MD, FRCS


Private Practice South Crest Hospital Tulsa, Oklahoma

vii

viii

Contributing Authors

Giuseppe Catanuto, MD
Instituto Nazionale per lo Studio e la Cura dei Tumori Scuola di Oncologia Chirurgica Ricostructtiva Milan, Italy

Sydney R. Coleman, MD
Assistant Clinical Professor New York University Medical Center Director, Tribeca Plastic Surgery New York, New York

Therese Soballe Cermak, MD


Department of Pathology Georgetown University Hospital Washington, DC

Lawrence B. Colen, MD
Professor Department of Surgery Eastern Virginia Medical School Norfolk, Virginia

David W. Chang, MD, FACS


Professor of Plastic Surgery Department of Surgery University of Texas M.D. Anderson Cancer Center Houston, Texas

Melissa A. Crosby, MD
Assistant Professor Department of Plastic Surgery The University of Texas M.D. Anderson Cancer Center Houston, Texas

Constance M. Chen, MD
New York, New York

Laurie W. Cuttino, MD
Associate Professor Department of Radiation Oncology Virginia Commonwealth University Health System Richmond, Virginia

Pierre M. Chevray, MD, PhD


Adjunct Associate Professor Department of Surgery Baylor College of Medicine The Methodist Hospital Plastic Surgeon Houston, Texas

Steven P. Davison, MD
DAVinci Plastic Surgery Washington, DC

Armando Chiari, Jr., MD


Brazil

Emmanuel Delay, MD, PhD


Department of Plastic and Reconstructive Surgery Lon Brard Center Lyon, France

Minas T. Chrysopoulo, MD
Plastic, Reconstructive, and Microsurgical Associates of South Texas San Antonio, Texas

Daniel Del Vecchio, MD, MBA


Back Bay Plastic Surgery Boston, Massachusetts

Mark W. Clemens, MD
Department of Plastic Surgery Georgetown University Hospital Washington, DC

Albert De Mey, MD
Professor Department of Plastic Surgery Free University, Brussels Brussels, Belgium

Costanza Cocilovo, MD
Assistant Professor of Surgery Department of Plastic Surgery Georgetown University Hospital Washington, DC

Richard V. Dowden, MD
Department of Plastic Surgery Cleveland Clinic Hillcrest Hospital Mayeld Heights, Ohio

Mark A. Codner, MD
Clinical Associate Professor Department of Plastic Surgery Emory University Atlanta, Gerogia

Ivica Ducic, MD, PhD


Professor Chief, Peripheral Nerve Surgery Department of Plastic Surgery Georgetown University Hospital Washington, DC

Hiram S. Cody, III, MD


Attending Surgeon, Breast Service Department of Surgery Memorial Sloan-Kettering Cancer Center Professor of Clinical Surgery The Weill Medical College of Cornell University New York, New York

Jennifer Eng-Wong, MD, MPH


Assistant Professor Department of Internal Medicine Lombardi Comprehensive Cancer Center Medical Oncologist Georgetown University Hospital Washington, DC

Michael Cohen, MD
Department of Plastic Surgery Georgetown University Medical Center Washington, DC

Contributing Authors

ix

Karen Kim Evans, MD


Division of Plastic Surgery Georgetown University Medical Center Washington, DC

James C. Grotting, MD
Clinical Professor of Plastic Surgery University of Alabama at Birmingham Grotting Plastic Surgery Birmingham, Alabama

Elizabeth D. Feldman, MD
Division of Breast Surgery Georgetown University Hospital Washington, DC

Geoffrey C. Gurtner, MD, FACS


Professor Department of Surgery Stanford University Stanford, California

Neil A. Fine, MD
Clinical Associate Professor Department of Plastic Surgery Northwestern University Feinberg School of Medicine Northwestern Memorial Hospital Chicago, Illinois

Elizabeth J. Hall-Findlay, MD, FRCSC


Private Practice Banff, Alberta, Canada

Moustapha Hamdi, MD, PhD Diane Franck, MD


Resident Department of Plastic Surgery Brugmann University Hospital Brussels, Belgium Professor Department of Plastic and Reconstructive Surgery Gent University Hospital Gent, Belgium Edith Cavell Medical Institute Brussels, Belgium

Marianne A. Fuller, RN
Clinical Manager Cleveland Clinic Cleveland, Ohio

Dennis C. Hammond, MD
Clinical Assistant Professor Department of Surgery Michigan State University College of Human Medicine East Lansing, Michigan Associate Program Director Plastic and Reconstructive Surgery Grand Rapids Medical Education Partners Grand Rapids, Michigan

Allen Gabriel, MD
Director of Research Department of Plastic Surgery Loma Linda University Medical Center Loma Linda, California

Onelio Garcia, Jr., MD, FACS


Voluntary Assistant Professor Division of Plastic Surgery University of Miami, Miller School of Medicine Miami, Florida Chief, Division of Plastic Surgery Palmetto General Hospital Hialeah, Florida

Neal Handel, MD, FACS


Associate Clinical Professor Division of Plastic Surgery David Geffen School of Medicine University of California at Los Angeles Los Angeles, California Santa Barbara Cottage Hospital Santa Barbara, California

Caroline A. Glicksman, MD
Associate Clinical Professor Department of Plastic Surgery Jersey Shore University Medical Center Neptune City, New Jersey

Catherine M. Hannan, MD
Resident Department of Plastic Surgery Georgetown University Hospital Washington, DC

Joo Carlos Sampaio Ges, MD, PhD


Instituto Brasileiro de Controle do Cancer So Paulo, Brazil

Barbara B. Hayden, MD
Santa Monica, California

Per Hedn, MD Jesse A. Goldstein, MD, MPH


Resident Department of Plastic Surgery Georgetown University Hospital Washington, DC Associate Professor Karolinska Instiutet Chief Department of Plastic Surgery Akademikliniken Stockholm, Sweden

Ruth Maria Graf, MD


Assistant Professor Department of Plastic Surgery Federal University of Paran Curitiba, Brazil

Christopher L. Hess, MD
Division of Plastic Surgery Georgetown University Medical Center Washington, DC

Contributing Authors

Saul Hoffman, MD
Fifth Avenue Center for Aesthetic Surgery New York, New York

R. Michael Koch, MD
Assistant Professor Department of Surgery New York Medical College Attending Surgeon Division of Plastic Surgery West Chester Medical Center Valhalla, New York

Karen M. Horton, MD
Division of Microsurgery and Department of Plastic Surgery California Pacic Medical Center San Francisco, California

Michael A. Howard, MD
Clinical Assistant Professor Section of Plastic Surgery University of Chicago Pritzker School of Medicine Chicago, Illinois North Shore University Health System Northbrook, Illinois

Steven J. Kronowitz, MD, FACS


Professor Department of Plastic Surgery The University of Texas M.D. Anderson Cancer Center Houston, Texas

Ethan E. Larson, MD
Department of Plastic Surgery Georgetown University Hospital Washington, DC

Dennis J. Hurwitz, MD
Clinical Professor of Plastic Surgery University of Pittsburgh Medical School Center Attending Plastic Surgeon Magee-Womens Hospital Pittsburgh, Pennsylvania

Claude Lassus, MD
Attending Plastic Surgeon University Hospital NICE Saint Paul France

Matthew L. Iorio, MD
Department of Plastic Surgery Georgetown University Hospital Washington, DC

Peter Ledoux, MD
Plastic Reconstructive and Microsurgical Associates of South Texas San Antonio, Texas

Claudine J. D. Isaacs, MD
Associate Professor of Medicine Lombardi Comprehensive Cancer Center Georgetown University Washington, DC

Valerie Lemaine, MD
Memorial Sloan-Kettering Cancer Center New York, New York

Jason C. Levine, MS
University of Wisconsin, Milwaukee Milwaukee, WI

F. Frank Isik, MD, FACS


Seattle, Washington

Joshua L. Levine, MD Jeffery M. Jacobson, MD


Department of Plastic Surgery Georgetown University Hospital Washington, DC Center for Microsurgical Breast Reconstruction New York, New York

Joan E. Lipa, MD, MSc, FRCS


Associate Professor David Geffen School of Medicine at UCLA Division of Plastic & Reconstructive Surgery University of California, Los Angeles Los Angeles, California

M. Renee Jespersen, MD
Georgetown University Medical Center Washington, DC

Mark Jewell, MD
Eugene, Oregon

Frank Lista, MD
Medical Director The Plastic Surgery Clinic Mississauga, Ontario, Canada

Marwan R. Khalifeh, MD
Assistant Professor Department of Surgery Johns Hopkins University School of Medicine Baltimore, Maryland Senior Partner Ivy Plastic Surgery Associates Chevy Chase, Maryland

J. William Little, MD
Clinical Professor of Surgery Department of Surgery Georgetown University Medical Center Washington, DC

Roger K. Khouri, MD, FACS


Chief Director Miami Breast Center Key Biscayne, Florida

Minetta C. Liu, MD
Associate Professor Director, Translational Breast Cancer Research Lombardi Comprehensive Cancer Center Georgetown University Washington, DC

Contributing Authors

xi

Albert Losken, MD, FACS


Associate Professor Division of Plastic and Reconstructive Surgery Emory University Atlanta, Georgia

John McCraw, MD
Professor of Surgery Department of Surgery University of Mississippi Medical Center Jackson, Mississippi

Maria M. LoTempio, MD
New York, New York

Juan Diego Mejia, MD


Private Practice Medellin, Colombia

Daniel P. Luppens, MD
Atlantic Plastic Surgery Salisbury, Maryland

Nathan G. Menon, MD
Department of Plastic Surgery Georgetown University Hospital Washington, DC

Antonio Luiz V. Macedo


Hospital Israelita Albert Einstein So Paulo, Brazil

Ali N. Mesbahi, MD
Division of Plastic Surgery Georgetown University Medical Center Washington, DC

Erini Makariou, MD
Associate Professor and Chief, Breast Imaging Department of Radiology Georgetown University Hospital Washington, DC

Joseph Michaels V, MD
Monarch Aesthetic and Reconstructive Plastic Surgery North Bethesda, Maryland

Donna-Marie E. Manasseh, MD
Breast Surgery Betty Lou Ourisman Breast Health Center Georgetown University Medical Center Washington, DC

Michael J. Miller, MD
Professor Division of Plastic Surgery The Ohio State University Chief, Division of Plastic Surgery The Ohio State University Medical Center Columbus, Ohio

Daniel A. Marchac, MD
Ancien Chef de Clinique a la Faculte Chirurgien attendant Consultant de lHopital Necker Professeur Associe au College de Medecine des Hopitaux de Paris Paris, France

Martin Jeffrey Moskovitz, MD


Image Plastic Surgery Paramus, New Jersey

Alessandra Marchi, MD
Regional Center for Breast Reconstruction Verona, Italy

Antonio Aldo Mottura, MD


Associate Professor of Surgery Universidad de Cordoba Cordoba, Argentina

Derek L. Masden, MD
Resident Department of Plastic Surgery Georgetown University Hospital Washington, DC

Jefferson E. C. Moulds, MD
Associate Professor of Clinical Radiation Medicine Georgetown University Washington, DC Radiation Oncologist Reston Hospital Center Reston, Virginia

G. Patrick Maxwell, MD
Baptist Medical Nashville, TN

James W. May, Jr., MD


Department of Plastic Surgery Massachusetts General Hospital Department of Surgery Harvard Medical School Boston, Massachusetts

Alexandre Mendona Munhoz, MD


Assistant Professor Department of Plastic Surgery University of Sao Paulo Sirio-Libanes Sao Paulo, Brazil

Colleen M. McCarthy, MD
Assistant Professor of Surgery Plastic and Reconstructive Surgery Weill Cornell Medical Center Memorial Sloan-Kettering Cancer Center New York, New York

Maurice Y. Nahabedian, MD, FACS


Associate Professor Department of Plastic Surgery Georgetown University Washington, DC

xii

Contributing Authors

Farzad R. Nahai, MD
Assistant Clinical Professor Division of Plastic Surgery Emory University School of Medicine Department of Surgery Piedmont Hospital Atlanta, Georgia

Christopher Vincent Pelletiere, MD


Private Practice Barrington Plastic Surgery, LTD. Inverness, Illinois Chief, Division of Plastic Surgery Northwest Community Hospital Arlington Heights, Illinois

Foad Nahai, MD, FACS


Clinical Professor of Plastic Surgery Department of Plastic Surgery Emory University Atlanta, Georgia

Angela Pennati, MD
Instituto Nazionale per lo Studio e la Cura dei Tumori Milan, Italy

Beth N. Peshkin, MS, CGC


Associate Professor Department of Oncology Georgetown University Washington, DC

James D. Namnoum, MD
Atlanta Plastic Surgery Atlanta, Georgia

Chet Nastala, MD, FACS


Plastic Reconstructive and Microsurgical Associates of South Texas San Antonio, Texas

Steven M. Pisano, MD
Plastic Reconstructive and Microsurgical Associates of South Texas San Antonio, Texas

Maurizio Nava, MD
Instituto Nazionale per lo Studio e la Cura dei Tumori Milan, Italy

Jason K. Potter, MD
Southwestern Medical Center Dallas, Texas

Maria Ceclia Closs Ono, MD


Plastic Surgeon Member of the Brazilian Society of Plastic Surgery Curitiba, Brazil

Christian A. Prada, MD
Division of Plastic Surgery Georgetown University Medical Center Washington, DC

Kristina OShaughnessy, MD
Plastic Surgery Chief Resident Department of Surgery Northwestern University Feinberg School of Medicine Chicago, Illinois

Julian J. Pribaz, MD, FRCS


Professor Department of Surgery Harvard Medical School Department of Surgery Brigham and Womens Hospital Boston, Massachusetts

David Otterburn, MD
Division of Plastic and Reconstructive Surgery Emory University Hospital Atlanta, Georgia

Andrea Pusic, MD
Memorial Sloan-Kettering Cancer Center New York, New York

Samir S. Rao, MD Joseph Ottolenghi, MD


Instituto Nazionale per lo Studio e la Cura dei Tumori Milan, Italy Georgetown University Medical Center Washington, DC

Elan Reisin, MD Pranay M. Parikh, MD


Department of Plastic Surgery Georgetown University Hospital Washington, DC Reisin West Institute Chevy Chase, Maryland

Neal R. Reisman, MD
Clinical Professor of Plastic Surgery Baylor College of Medicine Chief, Plastic Surgery St. Lukes Episcopal Hospital Houston, Texas

Julie E. Park, MD
Assistant Professor of Surgery Section of Plastic and Reconstructive Surgery The University of Chicago The University of Chicago Medical Center Chicago, Illinois

Egidio Riggio, MD
Instituto Nazionale per lo Studio e la Cura dei Tumori Milan, Italy

Ketan M. Patel, MD
Resident Physician Department of Plastic Surgery Georgetown University Hospital Washington, DC

Gino Rigotti, MD
Director Plastic Surgery, Burn Unit, Regional Center for Breast Reconstruction Azienda Ospedaliera Universitaria di Verona Verona, Italy

Contributing Authors

xiii

Geoffrey L. Robb, MD
Professor and Chair Department of Plastic Surgery The University of Texas M.D. Anderson Cancer Center Houston, Texas

Mitchel Seruya, MD
Resident Department of Plastic Surgery Georgetown University Hospital Washington, DC

Julia H. Rowland, MD
Director, Ofce of Cancer Survivorship National Institutes of Health Bethesda, Maryland

Minal Shah, MD
Hematologist/Medical Oncologist St. Marys Hospital Leonardtown, Maryland

J. Peter Rubin, MD
Director, Body Contouring Program Associate Professor of Surgery Division of Plastic Surgery University of Pittsburgh Pittsburgh, Pennsylvania

Kenneth C. Shestak, MD
Associate Professor of Plastic Surgery Department of Surgery University of Pittsburgh School of Medicine Magee-Womens Hospital Pittsburgh, Pennsylvania

James J. Ryan, MD
Cockeysville, Maryland

Melvin J. Silverstein, MD
Professor of Surgery Department of Surgical Oncology Keck School of Medicine University of Southern California Los Angeles, California Director, Hoag Breast Program Hoag Memorial Hospital Presbyterian Newport Beach, California

Amer Saba, MD
Division of Plastic Surgery Georgetown University Medical Center Washington, DC

Alesia P. Saboeiro, MD
Attending Physician Department of Surgery New York Downtown Hospital New York, New York

Baljit Singh, MD, MBBS


Associate Professor Director of Breast Pathology Department of Pathology New York University Langone Medical Center New York, New York

Michael Saint-Cyr, MD
Assistant Professor Southwestern Medical Center Dallas, Texas

Navin K. Singh, MD, MBA, PACS


Clinical Assistant Professor Department of Plastic Surgery Johns Hopkins University Sibley Memorial Hospital Chevy Chase, Maryland

C. Andrew Salzberg, MD
Associate Professor Department of Surgery New York Medical College Chief, Division of Plastic Surgery Westchester Medical Center Valhalla, New York

Sumner A. Slavin, MD
Department of Surgery Beth Israel Deaconess Medical Center Brookline, Massachusetts

Anousheh Sayah, MD
Department of Radiology Georgetown University Medical Center Washington, DC

David H. Song, MD, MBA


Professor of Surgery Section of Plastic Surgery University of Chicago Chief, Department of Surgery University of Chicago Medical Center Chicago, Illinois

Adam D. Schaffner, MD
Clinical Assistant Professor of Otorhinolaryngology Weill Cornell Medical College New York, New York

Michael Schean, MD
Atidim Medical Center Tel Aviv, Israel

Andrea Spano, MD
Instituto Nazionale per lo Studio e la Cura dei Tumori Milan, Italy

Jamie Schwartz, MD
Department of Plastic Surgery Georgetown University Hospital Washington, DC

Scott L. Spear, MD, FACS


Professor and Chairman Department of Plastic Surgery Georgetown University Hospital Washington, DC

xiv

Contributing Authors

Louis L. Strock, MD, FACS


Fort Worth, Texas

Robert L. Walton, MD
Plastic Surgery Chicago Chicago, Illinois

Simon G. Talbot, MD
Department of Plastic Surgery Brigham and Womens Hospital Boston, Massachusetts

Justin E. West, MD
Department of Plastic Surgery Breast Care and Imaging Center Orange, California

Andr Ricardo DallOglio Tolazzi, MD


Plastic Surgeon of the Plastic Surgery Unit of Federal University of Paran Curitiba, Brazil

Pat Whitworth, MD
Private Practice Nashville, Tennessee

Koenraad Van Landuyt, MD, PhD


Associate Professor Department of Plastic Surgery Gent University Hospital Gent, Belgium

Shawna C. Willey, MD
Director, Betty Lou Ourisman Breast Health Center Associate Professor of Clinical Surgery Department of Surgery Georgetown University Medical Center Washington, DC

Julie V. Vasile, MD
Associate Adjunct Surgeon Department of Plastic Surgery New York Eye and Ear Inrmary New York, New York Attending Surgeon Department of Surgery Stamford Hospital Stamford, Connecticut

Victor W. Wong, MD
Postdoctoral Research Fellow Stanford University Stanford, California

Michael R. Zenn, MD
Vice Chief Department of Plastic and Reconstructive Surgery Duke University Medical Center Durham, North Carolina

Mark L. Venturi, MD
McLean, Virginia

Christophe Zirak, MD Frank A. Vicini, MD, FACR


Clinical Professor Oakland University William Beaumont Hospital School of Medicine Chief of Oncology William Beaumont Hospital Royal Oak, Michigan Resident Department of Plastic Surgery Brugmann University Hospital Brussels, Belgium

Foreword

Dr. Scott Spear has written a phenomenal, one of a kind book on the comprehensive management of all aspects of breast disease from oncologic diseases to all aspects of reconstruction, cosmetic breast surgery and breast reduction all in one text. This unique text has evolved into the gold standard as it enters its third edition. By using a multidisciplinary approach in the management of complex problems of the breast, this book surpasses what can be done by any one surgical specialty text. Dr. Spear had the foresight to begin this journey over a decade ago when he published his rst edition in 1998 as well as his second edition along with superb associate editors Drs. Shawna Willey, Director of Breast Health Center at Georgetown University Medical Center, Department of Surgery; Geoffrey L. Robb, Professor and Chair, Department of Plastic Surgery at the University of Texas M.D. Anderson Cancer Center; Dennis C. Hammond, Center for Breast and Body Contouring, Grand Rapids, Michigan; and Maurice Y. Nahabedian, Associate Professor in the Department of Plastic Surgery at Georgetown University Medical Center. This textbook has become the bible for specialties dealing with diseases of the breast from breast cancer screening and management and prevention to an oncologic approach to breast surgery as well as the reconstructive aspects and renements and advancements in breast surgery. This book reveals the paradigm shift in how breast patients are managed and that it is no longer done by one specialty in isolation. A multidisciplinary approach to the management of breast patients denitely improves care and outcomes in breast cancer. Dr. Spear is a uniquely talented surgeon in that he has tremendous organizational and people skills to assemble some of the most well known authors in the world in each

area from breast cancer to cosmetic surgery of the breast for this book. I have known Dr. Spear as a friend and colleague for almost twenty years and have followed his career as he became Chairman of Plastic Surgery at Georgetown University Hospital and developed a superb department with his unique administrative people skills and surgical talents. He has been a tremendous role model for all of us in the eld of plastic surgery of how plastic surgery can strive for excellence and thrive in an environment where innovation, ingenuity and discovery are important. Dr. Spear excels in all of these areas. This book, which contains the new adjunct and promising therapies in the management of breast cancer as well as renements from perforator aps for breast reconstruction to minimally invasive procedures for breast reshaping to the evolving new modalities for breast augmentation and renements in breast implants as well as the potential for lipoaugmentation with fat transfer, has now become a classic text to which all others must be compared in the future. I, along with the entire specialties of surgery and plastic surgery, applaud Dr. Spear and his associate editors for this truly remarkable, third edition text on surgery of the breast. Rod J. Rohrich, MD, FACS Professor and Chairman Crystal Charity Ball Distinguished Chair in Plastic Surgery Warren and Betty Woodward Chair in Plastic and Reconstructive Surgery Department of Plastic Surgery University of Texas Southwestern Medical Center Dallas, Texas

xv

Foreword to 2nd Edition

A decade ago when Dr. Spear asked me to contribute to a new book on breast surgery as associate editor, I demurred. In the first place, did the world really need another textbook on plastic surgery of the breast? It would be a lot of work, especially for him; was he prepared for all the tardy contributors who would have to be coaxed and wheedled and threatened to keep on any sort of publication schedule? And secondly, what could I contribute? I was at a point in my career where my clinical interests had turned away from breast surgery toward the rethinking that was beginning to sweep through the field of facial rejuvenation. Fortunately Dr. Spear persisted, of course, and the nal product was indeed a wonderful contribution to the specialty. Here for the rst time were all the attendant disciplines concerned with breast disease and deformity included in depth for the convenient review of the practicing plastic surgeon. Here also was a rich compendium of key surgical techniques within each of the various components that make up plastic surgery of the breast, presented by the most respected authorities worldwide. And all this in a single, tidy volume. Dr. Spear and I both trained with Dr. D. Ralph Millard, Jr., who penned the foreword for the rst edition. After leaving Miami, Dr. Spear spent fellowship training in Paris studying craniofacial surgery with Dr. Daniel Marchac. When I invited him to join me at Georgetown, it was with the thought that he would help develop this clinical area. But such is the nature of the diverse eld we call plastic surgery that we can never predict where the needs of the specialty will take us, however we try to dene our particular interests early in our careers. Such also was the case with Dr. Stephen Kroll, too early taken from us; despite thorough training in otorhinolaryngology before his plastic surgery residency with Dr. Spear and myself at Georgetown, his greatest contributions also fell to the eld of breast surgery. Dr. Spear took quickly to the breast surgery program at the Medical Center and became a key contributor and later lead author on the various breast papers that issued from our unit. After I taught myself dermal tattooing for nipple-areolar coloration, for example, it was Dr. Spear who went to the manufacturers to help develop a line of custom, premixed pigments for the convenient use of practicing plastic surgeons. When the silicone breast implant crisis took over the specialty in the early nineties, my reaction to the intrusion of politics into patient care was one of distaste and disillusionment, as I watched my

clinical results deteriorate overnight. I was not alone, of course; it was no coincidence, for example, that Dr. Rod Hester and I found ourselves independently developing new interests (and new midface lifts) in the wake of the controversy. But Dr. Spear saw opportunity in adversity, as he continued to labor within the system to make the best of a bad situation. Again he worked with the manufacturers to help develop saline implants of better design, but also to foster the necessary studies to support the return of the silicone implant, a looming if long-delayed reemergence that will ultimately owe a good deal to his individual efforts. The fact that we so soon have a second and much expanded edition of this valuable work is reective of Dr. Spears managerial efciency. In the little more than a decade since Dr. Spear succeeded me at Georgetown, for example, that same efciency brought impressive growth to the plastic surgery division, culminating in its recent graduation to departmental status, joining Georgetown to an appallingly small club of plastic surgery departments within the nations many university medical centers. The associate editors for this second edition, all surgeons directly involved in surgery of the breast, have appropriately grown to four for this much larger offering. The three plastic surgeons, Drs. Robb, Hammond, and Nababedian, are all well-known to the specialty, each bringing a special expertise to the overall project. The general surgeon, Dr. Willey, brings a woman surgeons insight to overall matters of breast health. The new edition has grown by half, with the total number of chapters more than a hundred, over one-third of which are entirely new . . . reecting the latest concepts and emergent techniques of the past decade. Most of the remaining chapters have been extensively rewritten as well, to reect the forward progress of the same period. Two volumes, of course, are now required to contain the added information. I am certain this expanded and timely second edition will immediately prove not only valuable, but indeed indispensable to any practicing plastic surgeon who operates on the breast. And when I contemplate this handsome, well-edited set and nger through the many chapters with their intriguing titles and beautiful clinical photographs and results, I must admitas a plastic surgeon with a clinical practice now limited to surgical rejuvenation of the face . . . I must admit a certain wistfulness. . . . J. William Little, MD

xvii

Foreword to 1st Edition

This book is one of a kind. Two of the authors, Editor Scott L. Spear and Associate Editor John William Little, were sought as residents for our Plastic Surgery Division at the University of Miami School of Medicine because of their record of superiority in collegiate leadership, scholarship, and athletics, graduation from outstanding medical schools, and completion of sound training in general surgery at superior medical centers. Bill Little also had completed a plastic surgery residency under the great Cliff Kiehn before coming to our program. During their residency, they both excelled in applying principles to the planning and execution of plastic surgery. It was obvious that both were destined for important roles in their specialty. Bill Little became program chairman of plastic surgery at Georgetown Medical Center and served with distinction for 10 years, at which time Scott Spear took over for him. During the past 20 years, as evidenced by publications, symposia, and teaching sessions, Drs. Little and Spear have had enormous experience in plastic surgery of the breast at Georgetown University. Despite this, I challenged Dr. Spear to tell me why, specically, he was writing this book. These are his comments, which give insight into the real purpose and true value of this book. As one of your trainees and a descendent of the GilliesMillard School of plastic surgery, I have wanted to, hoped to, and tried to play my part in passing on to the present and future plastic surgeons the importance of key principles. I have been impressed in a wide range of plastic surgery endeavors, that only a handful of plastic surgeons are able to combine principles and art, particularly in reconstructive surgery. Surgery of the breast as it is performed currently is in need of much of the same focus that cleft lip and palate surgery received with your books, Cleft Craft. Also, I borrowed the title of your rst book, The Principles and Art of Plastic Surgery and will bring principles of plastic surgery into play in a broadly aimed textbook on surgery of the breast, in an attempt to help surgeons do their job and ultimately help patients to get better results. In addition, I have been struck that the eld of breast surgery needed a textbook which could cover the whole gamut of breast surgery from the surgical point of view. What is available

currently in bookstores is focused either on purely cosmetic surgery, reconstructive surgery, or ablative surgery. No one has tied these three together; so we have oncologic surgeons who do not understand aesthetic principles, we have aesthetic surgeons who do not understand oncologic or reconstructive principles, and we have reconstructive surgeons who do not understand aesthetic or oncologic principles. Thus, this book is divided into four sections, including oncologic surgery, reconstructive surgery, and cosmetic surgery. The reason that the book is multiauthored is that no one that I know of can write all three sections authoritatively. I expect that, in the future, breast surgery will become more and more of a specialty by itself with one surgeon working in all three areas rather than having two or three surgeons involved. In that sense, the same surgeon might diagnose breast cancer, perform the biopsy, do the ablation, and nally perform the reconstruction. This trend is beginning to happen already in the United States with Grant Carlson at Emory University. It is also occurring in Europe, in both Italy and Germany. I see this textbook, therefore, as the fundamental text for this next generation of breast surgeons. Bill Wood, Chief of Plastic Surgery at Emory University, an expert in breast oncology, was instrumental in helping to organize the content and authors of the oncology section. John W. Littles important chapters, by his specic analysis, rely less on scientic discussion and documentation than on surgical art, the personal and empiric accumulation of insight into the operations. His contributions are memorable. Marc Lippman, one of the worlds leading authorities on breast cancer, is a medical oncologist and was head of that portion at the National Institutes of Health for many years before coming to Georgetown to run the Lombardi Cancer Center. His chapter is concerned with the future trends in management of breast cancer in the next millennium. Thus, you will nd this book complete in its coverage, detailed in its description, and enjoyable in its presentation. D. Ralph Millard, Jr., M.D., F.A.C.S., Hon. F.R.C.S. Ed, Hon. F.R.C.S. Eng., O.D. Ja. Light-Millard Professor and Chairman Emeritus University of Miami School of Medicine Miami, Florida

xix

Preface

The primary mission of a physician is to help his or her patients. The higher mission of a medical textbook is to help other physicians help even more patients. Although I have been asked before to write other books on other medical subjects, I preferred to wait until I thought I had something truly substantial to add on a subject that would help other surgeons in some special way that other text had not yet accomplished. As mentioned, with the many changes in breast surgery during the last two decades and the increasing need for interspecialty collaboration and cooperation, the seeds of this book were thus sown. I saw an opportunity to write and edit a unifying text/atlas that embraced the plastic surgery principles as espoused by Gilles and Millard and yet span the entire breadth of this discipline from breast oncology to breast augmentation. At the same time, in the Millard tradition, my goal is to show others that beautiful or normal-looking results are not only obtainable but critical for this important area. This book is thus written for plastic surgeons, general surgeons, gynecologists, oncologists, or anyone else who is looking for a unied source of information for practical and principled surgical management of the breast. Although the section dealing with oncology is primary text in nature, most of the remaining chapters are in atlas format, thus allowing the reader to pursue the surgical approach espoused within the text. In total, there are over 130 chapters with over 150 contributing authors. In order to have the most expertise in as many areas as possible, we chose a multiauthored approach to the subject rather than a single-authored text. With a singleauthor book, the scope necessarily would have been more limited or the tone less authoritative. The atlas format is meant to provide a how-to outline for many procedures. The text chapters, on the other hand, are meant as resources regarding important oncologic, reconstructive, or other principles. The

rst edition of this text was developed with the help of Bill Wood, Chief of Surgery at Emory University in Atlanta, and Bill Little, my predecessor as Chief of Plastic Surgery at Georgetown University. The second edition included some additional new talent, who have returned for the third edition. I am grateful to Shawna Willey, head of the Breast Oncology Section at Georgetown University Hospital; Dennis Hammond, a practicing plastic surgeon in Grand Rapids, Michigan; Maurice Nahabedian, my plastic surgery colleague here at Georgetown; and Geoff Robb, Chief of Plastic Surgery at the M.D. Anderson Hospital, all of whom have helped me tremendously as associate editors of this third edition. In the preface to the rst edition, I mentioned key principles as proposed by Ralph Millard, which I have hoped to carry forward in my practice and in this text. Just to review, some of the most critical and relevant principles that are highlighted in this text include: Know the ideal beautiful normal. Diagnose before treating. Tissue losses should be replaced in kind whenever possible. Reconstruct in units. Make a plan, a pattern, and a second plan (a lifeboat). Consider the secondary donor area. Follow up with a critical eye. Teaching our specialty is its best legacy.

Although there are other good books written about the breast, none that I know of has tackled this diverse subject so broadly and yet tried to focus on the critical issues in so many different areas. If this text helps other physicians and, in particular, other surgeons treat their patients, then I will feel that it has succeeded.

xxi

Acknowledgments

As the work in preparing this third edition of this textbook comes to a close, the task of acknowledging those who have helped along the way certainly becomes more challenging. Where to start? So, lets start with my associate editors who have each given up countless hours and expertise to contribute their own chapters, and shape, edit and discuss the chapters of others in their respective sections. Doctors Hammond, Nahabedian, Robb, and Willey are each well-respected authorities in their respective elds and could, and in fact, have written their own texts. So to each of you: Thank you, really. Similarly, to the over 150 authors who also contributed to these pages: Thank you. Only those who have ever endeavored to publish or write a medical text can appreciate how much uncompensated work goes into these efforts. Then there are the residents and fellows who work with me and all the other associate editors. I make no bones about the fact that surgery is not a one man act. My patients know that I rely heavily on a team of residents and fellows to help with the

surgery, help take care of the patients, and even help with scholarly things such as this textbook. Thanks to all of you. I do appreciate it even if I dont always show it. How about my professional staff of nurses, physician assistants, administrative assistants, and even administrators? So thanks to all of you, especially Sonia Alexander, Lisa Grollman, Mary Beth Brubeck, Cathalene Blake, Joni Douglas, Karen Johnson, Benson Won, and Mark Pollard. You all know that I could not do this work without your tireless efforts, day in and day out. Finally, let me mention my industry partners and associates. Often maligned or taken for granted, my partners in industry whether book publishers, implant manufacturers, pharmaceutical companies, or otherscreate and provide the products that allow us to do our job, and support us with education, grants, and other tools that make our work possible. So a special thanks to Hani Zeini, Lisa Colleran, and Rene Snowden who have helped me so much along the way.

xxiii

Contents

Contributing Authors vii Foreword xv Foreword to 1st Edition xvii Foreword to 2nd Edition xix Preface xxi Acknowledgments xxiii

9 Sentinel Node Biopsy and Axillary


Dissection . . . . . . . . . . . . . . . . . 107
HIRAM S. CODY III

10 Breast Conservation: Oncologic


Issues . . . . . . . . . . . . . . . . . . . . 118
COSTANZA COCILOVO

Volume 1
SECTION I: Oncology and Oncoplastic Surgery
1 The Epidemiology of Breast Cancer:
Incidence and Risk Factors . . . . . . . 3
CELIA BYRNE

11 Oncoplastic Surgery: Managing


Common and Challenging Problems . . . . . . . . . . . . . . . . . . 123
ALEXANDRE MENDONA MUNHOZ

12 Reconstruction of Partial
Mastectomy Defects: Classications and Methods . . . . . . . . . . . . . . . 140
ALBERT LOSKEN

13 Special Problems in the Treatment


and Reconstruction of Breast Cancer . . . . . . . . . . . . . . . . . . . . 165
ALBERT LOSKEN

2 Breast Cancer Screening and


Diagnosis . . . . . . . . . . . . . . . . . . 11
COSTANZA COCILOVO

3 Imaging of the Surgically Altered


Breast . . . . . . . . . . . . . . . . . . . . . 16
ERINI MAKARIOU AND ANOUSHEH SAYAH

14 The Osnabrueck Experience With


Reconstruction of the Partial Mastectomy Defect . . . . . . . . . . . 177
KLAUS E. BRUNNERT

4 Breast Cancer Diagnosis, Prognosis,


and Treatment in Augmented Women . . . . . . . . . . . . . . . . . . . . 35
NEAL HANDEL

15 Reconstruction of the Breast


Conservation Patient . . . . . . . . . 198
SUMNER A. SLAVIN

5 Pathology of Breast Disorders . . . . 48


BALJIT SINGH

16 Reduction Mammaplasty as Part


of Breast Conservation Therapy of the Large-breasted Patient . . . 213
SCOTT L. SPEAR, KETAN M. PATEL, AND PRANAY M. PARIKH

6 Dening and Managing the


High-risk Patient . . . . . . . . . . . . . 62
THERESE S. CERMAK AND JENNIFER ENG-WONG

17 Follow-up After Surgery for Primary


Breast Cancer: Breast-conserving Therapy and Mastectomy . . . . . . 218
ELIZABETH D. FELDMAN AND WAFA ALKHAYAL

7 Ductal Carcinoma In Situ: An


Oncoplastic Treatment Approach . . . 71
MELVIN J. SILVERSTEIN

8 Mastectomy for Breast Cancer . . . . 96


SHAWNA C. WILLEY AND DONNA-MARIE E. MANASSEH

18 Adjuvant Systemic Therapy . . . . . 228


MINAL SHAH, CLAUDINE J. D. ISAACS, AND MINETTA C. LIU

xxv

xxvi

Contents

19 Radiation Therapy Following


Breast-conserving Surgery . . . . . 242
LAURIE W. CUTTINO AND FRANK A. VICINI

30 One-stage Immediate Breast


Reconstruction With Adjustable Implants . . . . . . . . . . . . . . . . . . 357
HILTON BECKER

20 Invasive Carcinoma: Radiation


Therapy After Mastectomy . . . . . 255
JEFFERSON E.C. MOULDS

31 Immediate and Delayed Breast


Reconstruction With Shaped Adjustable Implants . . . . . . . . . . 376
MICHAEL SCHEFLAN

21 Hereditary Breast Cancer: Risk


Assessment, Genetic Testing, and Management Options . . . . . . . . . 264
BETH N. PESHKIN

32 Immediate Two-stage Breast


Reconstruction Using a Tissue Expander and Implant . . . . . . . . 388
LOUIS L. STROCK

22 Prophylactic Simple Mastectomy and


Reconstruction, Including Prosthetic, Latissimus, and Transverse Rectus Abdominus Myocutaneous Flap Techniques . . . . . . . . . . . . . . . . 277
DENNIS C. HAMMOND

33 Acellular Dermis-assisted Breast


Reconstruction . . . . . . . . . . . . . . 406
SCOTT L. SPEAR, PRANAY M. PARIKH, AND NATHAN G. MENON

23 Nipple-sparing Mastectomy and


Reconstruction: Indications, Techniques, and Outcomes . . . . . 287
SCOTT L. SPEAR, SHAWNA C. WILLEY, CATHERINE M. HANNAN, AND COSTANZA COCILOVO

34 Direct-to-Implant Breast
Reconstruction With Acellular Dermal Matrix . . . . . . . . . . . . . . 412
C. ANDREW SALZBERG AND R. MICHAEL KOCH

35 Delayed Two-stage Tissue Expander


Implant Breast Reconstruction . . . . . . . . . . . . . . 420
F. FRANK ISIK

24 Nipple-sparing Mastectomy . . . . . 298


G. PATRICK MAXWELL, PAT WHITWORTH, AND ALLEN GABRIEL

36 Breast Reconstruction With


Form-stable Implants . . . . . . . . . 429
MAURIZIO NAVA, ANGELA PENNATI, ANDREA SPANO, AND GIUSEPPE CATANUTO

25 Breast Cancer in Men: Oncologic and


Reconstructive Considerations . . 308
MAURICE Y. NAHABEDIAN

26 Psychological Impact of
Treatments for Breast Cancer . . . 313
JULIA H. ROWLAND

37 Skin-preserving Delayed-Immediate
Breast Reconstruction . . . . . . . . 438
STEVEN J. KRONOWITZ AND GEOFFREY L. ROBB

SECTION II: Breast Reconstruction


27 Informed Consent: Medicolegal
Considerations in Breast Surgery . . . . . . . . . . . . . . . . . . . 331
NEAL R. REISMAN

38 Immediate Two-stage Breast


Reconstruction Using Semilunar Expander and Purse-string Closure . . . . . . . . . . . . . . . . . . . 450
GINO RIGOTTI AND ALESSANDRA MARCHI

39 Prosthetic Reconstruction in the


Radiated Breast . . . . . . . . . . . . . 460
SCOTT L. SPEAR AND M. RENEE JESPERSEN

28 Silicone Gel Breast Implants . . . . 337


MICHAEL J. MILLER

40 Secondary Prosthetic Cases . . . . . 476


SCOTT L. SPEAR, M. RENEE JESPERSEN, AND ADAM D. SCHAFFNER

29 Breast Implants: Materials and


Manufacturing Past, Present, and Future . . . . . . . . . . . . . . . . . . . . 344
WILLIAM P. ADAMS, JR AND JASON K. POTTER

41 Recreating the Inframammary Fold:


The External Approach . . . . . . . . 492
JAMES J. RYAN

Contents

xxvii

42 Re-creating the Inframammary Fold:


The Internal Approach . . . . . . . . 497
SCOTT L. SPEAR, ALI N. MESBAHI, AND MICHAEL BECKENSTEIN

53 Breast Reconstruction With the


Unipedicle TRAM Operation: The Muscle-splitting Technique . . . . . 660
SCOTT L. SPEAR, CHRISTIAN A. PRADA, DEREK L. MASDEN, AND J. WILLIAM LITTLE

43 Recreating the Inframammary


Fold With the Supercial Fascial System . . . . . . . . . . . . . . 512
MAURIZIO NAVA, JOSEPH OTTOLENGHI, AND EGIDIO RIGGIO

54 Bilateral Transverse Rectus Abdominus


Myocutaneous Flaps . . . . . . . . . . 670
ONELIO GARCIA, JR.

44 Latissimus Dorsi Musculocutaneous


Flap Breast Reconstruction . . . . . 535
DENNIS C. HAMMOND

55 Free Transverse Rectus Abdominis


Myocutaneous Flap Breast Reconstruction . . . . . . . . . . . . . . 681
CHET L. NASTALA, STEVEN M. PISANO, MINAS T. CHRYSOPOULO, AND PETER R. LEDOUX

45 Endoscopic Delayed-Immediate
Autologous Reconstruction with Latissimus Muscle Only Flaps . . . 555
NEIL A. FINE AND KRISTINA OSHAUGHNESSY

56 Immediate Reconstruction After


Skin-sparing Mastectomy Through a Periareolar Approach . . . . . . . . 693
JOAN E. LIPA

46 The Latissimus Dorsi Flap


in Reconstruction of the Radiated Breast . . . . . . . . . . . . . 563
SCOTT L. SPEAR, JAY BOEHMLER, AND MARK W. CLEMENS

57 Immediate Reconstruction After Skinsparing Mastectomy Using the Omental Flap and Synthetic Mesh . . . . . . . 705
JOO CARLOS SAMPAIO GES AND ANTONIO LUIZ V. MACEDO

47 Breast Reconstruction With an


Autologous Latissimus Dorsi Flap With and Without Immediate Nipple Reconstruction . . . . . . . . 571
EMMANUEL DELAY

58 Abdominal Flaps and Implants . . 712


MAURICE Y. NAHABEDIAN

59 Transverse Rectus Abdominis


Myocutaneous Flaps With Preoperative Delay . . . . . . . . . . . 720
PAUL R. CALLEGARI

48 Aesthetic Subunits of the


Breast . . . . . . . . . . . . . . . . . . . . 597
STEVEN P. DAVISON AND MARK W. CLEMENS

60 Breast Reconstruction With Free


Tissue Transfer: An Algorithmic Approach . . . . . . . . . . . . . . . . . . 727
JULIE E. PARK AND DAVID H. SONG

49 Reconstruction of the Irradiated


Breast . . . . . . . . . . . . . . . . . . . . 607
SCOTT L. SPEAR, MATTHEW L. IORIO, AND PRANAY M. PARIKH

50 One-stage Reconstruction of the


Breast Using Autologous Tissue With Immediate Nipple Reconstruction . . . . . . . . . . . . . .623
LAWRENCE B. COLEN AND JOHN MCCRAW

61 Perforator Flaps in Breast


Reconstruction . . . . . . . . . . . . . . 736
MARK W. CLEMENS AND MAURICE Y. NAHABEDIAN

62 Anatomic Basis of Perforator


Flaps . . . . . . . . . . . . . . . . . . . . . 745
MICHEL SAINT-CYR

51 Bipedicle TRAM Flap


Reconstruction . . . . . . . . . . . . . . 639
KENNETH C. SHESTAK

63 Pedicled Perforator Flaps


in Breast Reconstruction . . . . . . . 757
MOUSTAPHA HAMDI

52 Transverse Rectus Abdominis


Myocutaneous Flap Reconstruction: The Single-pedicle, Whole-muscle Technique . . . . . . . . . . . . . . . . . 652
MICHAEL R. ZENN AND JAMES W. MAY, JR.

64 Musculofascial-sparing Transverse
Rectus Abdominis Musculocutaneous Flaps . . . . . . . . . . . . . . . . . . . . . 770
MICHAEL J. MILLER

xxviii

Contents

65 Deep Inferior Epigastric


Artery Perforator Flap Breast Reconstruction . . . . . . . . . . . . . 778
MARK W. CLEMENS AND MAURICE Y. NAHABEDIAN

76 Fat Injection to Correct Contour


Deformities in the Reconstructed Breast . . . . . . . . . . . . . . . . . . . . 904
SCOTT L. SPEAR AND ALI AL-ATTAR

66 The Superior Gluteal Artery


Perforator Flap in Breast Reconstruction . . . . . . . . . . . . . . 790
JULIE V. VASILE, ROBERT J. ALLEN, AND JOSHUA L. LEVINE

77 Lipomodeling of the Reconstructed


Breast . . . . . . . . . . . . . . . . . . . . 912
EMMANUEL DELAY

78 Surveillance Following Breast


Reconstruction . . . . . . . . . . . . . . 930
VALERIE LEMAINE, COLLEEN M. MCCARTHY, AND ANDREA PUSIC

67 The Inferior Gluteal Artery Perforator


Flap for Microsurgical Breast Reconstruction . . . . . . . . . . . . . . 803
CONSTANCE M. CHEN, MARIA M. LoTEMPIO, AND ROBERT J. ALLEN

79 Reconstruction of the Breast


Following Tumor Recurrence . . . 934
MELISSA A. CROSBY AND DAVID W. CHANG

68 The Supercial Inferior


Epigastric Artery Flap in Breast Reconstruction . . . . . . . . . . . . . . 808
PIERRE M. CHEVRAY

80 Stem Cells and the Breast . . . . . . 940


EDWARD P. BUCHANAN, VICTOR W. WONG, AND GEOFFREY C. GURTNER

81 Management of Chronic
Postoperative Breast Pain . . . . . . 947
IVICA DUCIC, ETHAN E. LARSON, AND MATTHEW L. IORIO

69 Gracilis Flaps for Breast


Reconstruction . . . . . . . . . . . . . . 818
KAREN M. HORTON

70 Options for Managing the Opposite


Breast in Breast Reconstruction . . . 830
JAMES D. NAMNOUM AND DAVID OTTERBURN

Volume 2
SECTION III: Reduction Mammaplasty and Mastopexy
82 Reduction Mammaplasty
and Mastopexy: General Considerations . . . . . . . . . . . . . . 955
DENNIS C. HAMMOND

71 Issues, Considerations, and


Outcomes in Bilateral Breast Reconstruction . . . . . . . . . . . . . . 838
ELISABETH K. BEAHM AND ROBERT L. WALTON

72 Nipple-Areola Reconstruction . . . 855


SCOTT L. SPEAR AND JUSTIN E. WEST

73 Considerations of Previous
Augmentation in Subsequent Breast Reconstruction . . . . . . . . 875
SCOTT L. SPEAR, MARK W. CLEMENS, AND MICHAEL A. HOWARD

83 Periareolar Benelli Mastopexy


and Reduction: The Round Block . . . . . . . . . . . . . . . . . . . . 960
LOUIS C. BENELLI

84 Mastopexy With Chest


Wallbased Flap and Pectoralis Muscle Loop . . . . . . . . . . . . . . . 972
RUTH GRAF, ANDR RICARDO DALLOGLIO TOLAZZI, THOMAS BIGGS, AND MARIA CECLIA CLOSS ONO

74 The Second Stage in Autologous


Breast Reconstruction . . . . . . . . 884
DAVID W. CHANG

75 Biomechanical Considerations
Following Breast Reconstruction With Abdominal Flaps . . . . . . . . 894
MAURICE Y. NAHABEDIAN, SCOTT L. SPEAR, AND CHRISTOPHER L. HESS

85 A Mastopexy Technique Without


Implants: Superolaterally Based Rotation Flap . . . . . . . . . . . . . . 985
BARBARA B. HAYDEN

Contents

xxix

86 Vertical Scar Breast Reduction


and Mastopexy Without Undermining . . . . . . . . . . . . . . . 990
CLAUDE LASSUS

100 Breast Reduction With the


Free Nipple Graft Technique . . . 1156
SCOTT L. SPEAR AND M. RENEE JESPERSEN

101 Reduction Mammoplasty


in the Irradiated Breast . . . . . . . 1170
SCOTT L. SPEAR AND AMER SABA

87 Vertical Mastopexy . . . . . . . . . . 1007


JUAN DIEGO MEJIA AND FOAD NAHAI

88 Vertical Mammaplasty for Breast


Reduction and Mastopexy . . . . . 1016
ALBERT DE MEY, DIANE FRANCK, AND CHRISTOPHE ZIRAK

102 Breast Reduction and Mastopexy


After Massive Weight Loss . . . . 1174
J. PETER RUBIN AND JOSEPH MICHAELS V

89 Vertical Mammaplasty With a


Short Horizontal Scar . . . . . . . 1025
DANIEL A. MARCHAC

103 Strategies in Breast Reduction


and Mastopexy After Massive Weight Loss . . . . . . . . . . . . . . . 1185
DENNIS J. HURWITZ

90 Breast Reduction by Liposuction


Alone . . . . . . . . . . . . . . . . . . . 1035
MARTIN MOSKOVITZ

104 Gynecomastia . . . . . . . . . . . . . . 1205


FRANK LISTA AND JAMIL AHMAD

91 Vertical Breast Reduction Using


the Superomedial Pedicle . . . . . 1045
ELIZABETH J. HALL-FINDLAY

105 Complications and Secondary


Corrections After Breast Reduction and Mastopexy . . . . . 1211
SCOTT L. SPEAR AND KAREN KIM EVANS

92 The Short Scar Periareolar


Inferior Pedicle Reduction Mammaplasty . . . . . . . . . . . . . . 1063
DENNIS C. HAMMOND

SECTION IV: Augmentation Mammaplasty


106 Augmentation Mammaplasty:
General Considerations . . . . . . . 1227
G. PATRICK MAXWELL, MATTHEW B. BAKER, AND ALLEN GABRIEL

93 The Circumvertical Breast


Reduction Technique . . . . . . . . 1078
A. ALDO MOTTURA

94 Inferior Pedicle Technique in Breast


Reduction: Basic Concepts . . . . 1088
NAVIN K. SINGH AND MARWAN R. KHALIFEH

107 The High Five Process:


Tissue-based Planning for Breast Augmentation . . . . . . . . 1246
WILLIAM P. ADAMS JR.

95 Inferior Pedicle Technique in Breast


Reduction: Practical Steps . . . . . 1097
SAUL HOFFMAN

96 Reduction Mammaplasty
Using the Central Mound Technique . . . . . . . . . . . . . . . . 1107
DANIEL P. LUPPENS AND MARK A. CODNER

108 The Augmentation Mammoplasty


Patient: Psychological Issues . . . 1254
REBECCA COGWELL ANDERSON AND JASON C. LEVINE

97 Reduction Mammaplasty Using


Medial Pedicles and Inverted-T Incisions . . . . . . . . . . . . . . . . . 1116
ETHAN E. LARSON AND MAURICE Y. NAHABEDIAN

109 Patient Education in Breast


Augmentation . . . . . . . . . . . . . 1261
CAROLINE A. GLICKSMAN

110 The Inframammary Approach to


Augmentation Mammaplasty . . . 1271
DENNIS C. HAMMOND

98 The L Short-scar Mammaplasty . 1128


ARMANDO CHIARI, JR. AND JAMES C. GROTTING

99 The No-vertical-scar Breast


Reduction . . . . . . . . . . . . . . . . 1144
SIMON G. TALBOT AND JULIAN J. PRIBAZ

111 The Periareolar Approach to


Augmentation Mammaplasty . . . 1277
SCOTT L. SPEAR, JEFFREY M. JACOBSON, AND ELAN REISIN

xxx

Contents

112 Subfascial Breast


Augmentation . . . . . . . . . . . . . 1283
RUTH MARIA GRAF, MARIA CECLIA CLOSS ONO, AND ANDR RICARDO DALLOGLIO TOLAZZI

123 Augmentation Mastopexy:


General Considerations . . . . . . . 1434
DENNIS C. HAMMOND

113 Transaxillary Breast


Augmentation . . . . . . . . . . . . . .1290
LOUIS L. STROCK

124 Managing Complications of


Augmentation Mammaplasty . . . 1447
NEAL HANDEL

114 Transumbilical Breast


Augmentation . . . . . . . . . . . . . 1300
RICHARD V. DOWDEN AND MARIANNE A. FULLER

125 Neo-subpectoral Technique for


Implant Malposition . . . . . . . . . 1473
SCOTT L. SPEAR, M. RENEE JESPERSEN, AND SAMIR S. RAO

115 Breast Augmentation With


Anatomic, High-cohesiveness Silicone Gel Implants (European Experience) . . . . . . . . . . . . . . . 1322
PER HEDN

126 Outcome Assessment of Breast


Distortion Following Submuscular Breast Augmentation . . . . . . . . 1481
SCOTT L. SPEAR AND JAIME SCHWARTZ

127 Bioprosthetic Materials for Plastic


Surgery of the Breast . . . . . . . . 1488
G. PATRICK MAXWELL AND ALLEN GABRIEL

116 The Highly Cohesive, Style 410


Form-stable Gel Implant for Primary Breast Augmentation . . . . . . . . 1346
BRADLEY P. BENGTSON

128 Acellular Dermal Matrix for the


Treatment and Prevention of Implant-associated Breast Deformities . . . . . . . . . . . . . . . 1495
SCOTT L. SPEAR AND MITCHEL SERUYA

117 Lipoaugmentation . . . . . . . . . . 1366


SYDNEY R. COLEMAN AND ALESIA P. SABOEIRO

118 Breast Augmentation and


Reconstruction Using BRAVA External Breast Expansion and Autologous Fat Grafting . . 1374
ROGER K. KHOURI AND DANIEL DEL VECCHIO

129 Correction of Capsular Contracture


After Augmentation Mammaplasty by Conversion to the Subpectoral or Dual-plane Position . . . . . 1503
SCOTT L. SPEAR AND MICHAEL COHEN

119 Augmentation Mammaplasty in the


Patient With Tuberous Breasts and Other Complex Anomalies . . . . 1401
DENNIS C. HAMMOND

130 The Inframammary Fold: Histologic


and Anatomic Description, Classication and Denitions, and Options for Repair and Reinforcement . . . . . . . . . . . . . 1510
BRADLEY P. BENGTSON

120 Augmentation Mammaplasty


in Women With Thoracic Hypoplasia . . . . . . . . . . . . . . . 1410
SCOTT L. SPEAR, JESSE A. GOLDSTEIN, AND CHRISTOPHER V. PELLETIERE

131 Revision Augmentation With


Anatomic Form-stable Silicone Gel Implants . . . . . . . . . . . . . . 1516
MITCHELL H. BROWN

121 Breast Reconstruction in Patients


With Poland Syndrome . . . . . . . 1416
JAMES D. NAMNOUM

132 Correction of Ptosis in the Previously


Augmented Breast . . . . . . . . . . 1532
NEAL HANDEL

122 Augmentation With Periareolar


Mastopexy . . . . . . . . . . . . . . . . 1425
SCOTT L. SPEAR AND MARK L. VENTURI

Index

1561

SECTION

Oncology and Oncoplastic Surgery

CHAPTER

1
The Epidemiology of Breast Cancer: Incidence and Risk Factors
In the United States, breast cancer comprises 27% of all new female cancers, and as such is the most common cancer among women and the second-leading cause of cancer mortality, explaining 15% of female cancer deaths (1). In the United States, an estimated 192,370 women were diagnosed with breast cancer and 40,170 women died from breast cancer in 2009 (1) (Fig. 1.1). Breast cancer incidence and mortality rates vary by race and ethnicity (2) (Fig. 1.2). Clearly breast cancer remains a substantial cause of morbidity and mortality, and there is need for continued efforts to better understand the etiology of the disease, maintain screening efforts, implement prevention strategies, and develop better treatments. It is important to consider what we know about breast cancer etiology already and how that relates to changes in breast cancer incidence and mortality. Our ability to understand greater details about specic breast cancer risk factors has improved in recent years with the published results from various large pooling studies that have combined data from numerous studies and detailed metaanalyses. While results from smaller studies may vary to some degree, combining the data from many studies has provided a better understanding of risk and has also allowed the determination of risk with small changes in exposure levels and in subgroups of women. Most of the studies presented have evaluated risk factors for invasive breast cancer. However, ductal carcinoma in situ (DCIS), a noninvasive disease that is believed to be a precursor lesion for invasive disease if not treated, shares many of the same risk factors. Some studies of breast cancer include invasive and DCIS cases together. Lobular carcinoma in situ seems to be more of a marker of susceptibility rather than a precursor lesion itself, and it does not share as many risk factors.

Celia Byrne

all, that pattern is not consistent for all age groups (3,4). It has been recognized for some time that African American women under the age of 40 years have a higher rate of invasive breast cancer (15.5/100,000) than White women (13.1/100,000), and then after age 40 years White women have a higher rate of invasive breast cancer (281.3/100,000 vs. 239.5/100,000) (3,4). For women under age 30 years the rate in African American women is 1.52 (95% condence interval [CI] 1.34 to 1.73) times that of White women (3). African Americans have the highest breast cancer mortality rates (33.5/100,000), followed by Whites (24.4/100,000), Native Americans (17.1/100,000), Hispanics (15.8/100,000), and Asians (12.6/100,000) (2). EARLY LIFE EVENTS Recent studies have suggested that breast cancer risk is impacted by early life events even prenatally, and the early life period in utero, in childhood, and in adolescence may potentially be an important window of risk for breast cancer when breast tissue may be more susceptible to carcinogenic exposures (5,6). Birth weight is positively associated with maternal sex hormones and insulin-like growth factor-1 (IGF-1) levels, both of which are involved in initiation and promotion of breast cancer (7). In a meta-analysis of studies examining early life factors and breast cancer risk, women with higher birth weights had an increased relative risk (RR) of 23% (95% CI 1.13 to 1.34) (8). Studies of birth length have also shown a positive correlation with breast cancer risk, with an overall summary estimate that longer infants have a RR of 1.28 (95% CI 1.11 to 1.48) compared to shorter infants (8). In contrast, offspring of women who developed preeclampsia or eclampsia are at decreased risk of developing breast cancer (9), with a RR of 0.48 (95% CI 0.30 to 0.78) (8). The associations with other measures of in utero exposure, such as being a twin, gestational age, and diethylstilbestrol exposure, are less consistent in associations across studies (5,6,8). AGE AT MENARCHE It has been long recognized that the younger a womans age at menarche, the higher is her risk of developing breast cancer (10). However, a recent study of the participants in the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial indicated that the magnitude of the association between age at menarche and breast cancer may not be as strong a predictor of breast cancer as previously considered. Age at menarche has been decreasing over time in the United States and in many developed and developing countries. The factors most inuencing age at menarche, such as the prevalence of obesity, also have been changing over time (11).

RISK FACTORS FOR BREAST CANCER


GENDER, AGE, AND RACE/ETHNICITY Gender and age are recognized as the strongest predictors of breast cancer incidence. The incidence in males is approximately 1% of the incidence rate in females (1). In a womans lifetime she has on average a probability of 1 in 8 of developing breast cancer by age 85 years. However, she has only a probability of 1 in 208 by age 39 years, a probability of 1 in 26 between ages 40 and 59 years, a probability of 1 in 29 between ages 60 and 69 years, and a probability of 1 in 16 from age 70 years and older (1). In the United States, race and ethnicity are also associated differentially with invasive breast cancer incidence rates. Overall, White women have the highest rate of invasive breast cancer (130.6/100,000), followed by African Americans (117.5/100,000), Hispanics (90.1/100,000), Asian Americans (89.6/100,000), and Native Americans (75.0/100,000) (2). While Whites have the highest incidence of breast cancer over-

Section I Oncology and Oncoplastic Surgery

44,500 44,000 43,500 43,000 42,500 42,000 41,500 41,000 40,500 40,000 39,500 39,000
19 19 19 19 19 19 19 19 19 19 20 20 20 20 20 20 05 20 06 90 91 92 93 94 95 96 97 98 99 00 01 02 03 04

Figure 1.1. Female breast cancer deaths in the


United States, 19902006. (Data from U.S. Mortality Data 19902006, National Center for Health Statistics, Centers for Disease Control and Prevention, 2009.)

AGE AT MENOPAUSE Earlier age at menopause has been associated with reduced risk of breast cancer (10). One theory linked age at menarche and age at menopause, suggesting that the longer a woman was exposed to premenopausal hormone levels (time between menarche and menopause), the greater was her risk. As with age at menarche, age at menopause has also been changing, with later age at menopause being more common (12). In the recent analysis from the PLCO cohort, women with later age at menopause (55 years) compared to those with early age at menopause (45 years) had a RR of 1.29 (1.03 to 1.62). Again the magnitude of the association was not as strong an association as anticipated from previous studies (11). REPRODUCTIVE HISTORY Age at rst birth is another breast cancer risk factor that has been changing over time in developed and developing countries (13). Part of the increase in breast cancer incidence dur140 120 100 80 60 40 20 0
an s an s In di an s hi te ic er ic La t W er in as s

ing the 1980s and 1990s can be attributed in part to this trend in delayed childbearing. Compared with women whose first full-term pregnancy was before age 20 years, breast cancer risk increased for women with each year that rst full-term pregnancy was delayed. Nulliparous women and those whose rst full-term pregnancy was at age 30 years or older typically had a 50% increased risk of breast cancer compared with those whose rst full-term birth was before age 20 years (10). Pregnancies that were not full term did not show the protective effect (10). Several studies have now shown a short-term transient increased risk associated with each pregnancy (14,15). Between 5 and 10 years after the pregnancy the protective effect can be seen (14). Given the differentiation that occurs in breast tissue with a full-term pregnancy, it was thought that this process protected against cancer initiation, while in women having a later-age rst birth the growth of existing cancer cells would be promoted. Concern was raised whether spontaneous or induced abortion would increase the risk of breast cancer. In an analysis of pooled data from 53 different studies no increased risk was seen with reported spontaneous or induced abortion (16). PARITY In addition to the effects of age at rst birth on reducing breast cancer risk, increased parity is associated with reduced breast cancer risk (10). The protective effect is seen more in older postmenopausal women (10). In an analysis of the Finnish National Population Registry among women born after 1937 who had at least ve biological children, short-term spacing between births (1 year) was associated with an increased risk of breast cancer compared to longer intervals (3 years) (15). However, unlike the previously reported protective association with increased parity, from studies conducted primarily among White women, a large prospective study in African American women (Black Womens Health Study) found an increased risk with high parity for women younger than 45 years and a decrease for those 45 years and older (17). These differential associations between parity and breast cancer risk might in part explain the crossover in breast cancer rates seen between African American and White women in the United States.

ic a

si an

fr ic

Breast Cancer Incidence/100,000

Breast Cancer Mortality/100,000

Figure 1.2. Breast cancer incidence and mortality in the United


States, 20012005, by race and ethnicity.

is

pa ni c

an

er

s/

Chapter 1 The Epidemiology of Breast Cancer

BREAST-FEEDING Results have been inconsistent from studies examining whether there is a separate protective effect with breast-feeding and breast cancer risk. Given the reduction in breast-feeding practices in the United States during most of the 20th century it is now believed that many of these studies lacked sufcient exposure prevalence to be able to evaluate the separate effects of breast-feeding from age at first birth and parity (10). In a reanalysis of 47 studies from 30 countries with data on 50,302 breast cancer cases and 96,973 controls, the relative risk for breast cancer decreased 4.3% for each 12 months of breastfeeding in addition to a 7.0% decrease for each birth (18). These researchers concluded that the longer a woman breastfed, the more she reduced her breast cancer risk, and that the lack of long-duration breast-feeding in the developed countries contributed to the higher rates of breast cancer (18). Thus, in addition to the health benets that breast-feeding holds for the infant, women may help to lower their breast cancer risk by maintaining breast-feeding for longer durations. FAMILY HISTORY OF BREAST CANCER Having a family history of breast cancer has been recognized as a risk factor for breast cancer that reects both shared genetic and shared environmental exposures within a family. While this is the breast cancer risk factor that is most recognized by the public, only about 11% of all breast cancer cases have a family history of the disease (19). Having any rst-degree family history (mother or sister with breast cancer) is associated with an approximate twofold increase in breast cancer risk. The risk increases with the number of affected relatives, with relative risks of 1.80 (95% CI 1.69 to 1.91), 2.93 (95% CI 2.36 to 3.64), and 3.90 (95% CI 2.03 to 7.49) with one, two, and three or more affected relatives, respectively (19). These strong associations with a multiplex family history provided the background for the search for specific genes within families that might explain the risk (see description of genetic risk factors). MIGRATORY STUDIES Breast cancer rates vary quite dramatically among different countries across the world. Furthermore, as individuals migrate from low-risk countries to high-risk countries their risk begins to increase within one or two generations (20). Breast cancer rates increased among women migrating to the United States from Asian countries with low national rates within one or two generations (20). These differences in rates between countries that would change with migration led to the speculation that environmental inuencesparticularly dietary factorswould be related to breast cancer risk. Stemming from correlation studies of dietary fat consumption in those countries and breast cancer rates, the leading theory is that dietary fat intake must be driving the increased breast cancer rates in the developed countries. As countries become more developed, their breast cancer rates often rise, becoming closer to that of the United States and Western Europe. NUTRITIONAL FACTORS A large pooling study of the effects of fat on breast cancer risk found no association between breast cancer and risk for total fat (pooled RR of 1.00; 95% CI 0.98 to 1.03) or most subtypes of fat, other than a weak association with saturated fat intake

(21). However, these studies were conducted primarily among postmenopausal women and had minimal data on dietary intake early in adult life. More recently, analysis of a large cohort of postmenopausal women in the NIH-AARP Diet and Health Study suggested that there may be a modest association between a twofold increase in percent energy from total fat and breast cancer, with a relative risk of 1.32 (95% CI 1.11 to 1.58) when corrected for measurement error (22). In a study of premenopausal women in the Nurses Health Study II (NHSII) a modest association was found between intake of animal fat and increased breast cancer risk, with a RR of 1.0, 1.28 (95% CI 1.00 to 1.64), 1.37 (95% CI 1.07 to 1.75), 1.54 (95% CI 1.20 to 1.97), and 1.33 (95% CI 1.02 to 1.73) for each quintile of increasing animal fat intake. It could be that the modest associations seen in these two studies are real and they were more evident due to the sufciently wide range in exposures (40% of calories from fat compared to 20% of calories from fat) in the NIH-AARP study and the evaluation of premenopausal women from the NHS II cohort who had exposures sufficiently early enough during their life time to impact their breast cancer risk. The Womens Health Initiative Dietary Modication Trial found a 9% reduction in breast cancer rates among women in the lowfat dietary pattern group compared to the control group after 8.1 years of follow-up. This modest association was also accompanied by a lower total caloric intake, lower body weight, and increased fruits and vegetables, ber, and folate compared to the control group. So it is difcult to attribute the change in rate to a change in dietary fat alone (23). While the association between fat and breast cancer is still controversial, it is prudent for a broad range of other health reasons to consume a diet low in calories, low in fat, and high in whole grains, with lots of fruits and vegetables, which might result in weight loss. ALCOHOL Numerous studies have now reported a modest increased risk of breast cancer with moderate alcohol consumption. A pooled analysis of prospective studies provided sufcient numbers of cases to be able to evaluate types of alcohol to see if effects differed and by quantity of alcohol consumed (24). Risk did not vary by type of alcohol, and for each 10 g/d of alcohol intake breast cancer risk increased by 1.09 (95% CI 1.04 to 1.13) (24). In a reanalysis of 53 studies the relative risk of breast cancer was 7.1% (95% CI 5.5% to 8.7%; p 0.00001) for each additional 10 g/d of alcohol consumed (25). Despite the fairly consistent associations between alcohol intake and increased breast cancer risk, it is not clear how alcohol intake increases risk. Alcohol intake has been reported to change circulating hormone levels, and this could be how it increases breast cancer risk, or the alcohol metabolites may be carcinogenic (26). Several studies (27) have found that among women with a high dietary folate intake alcohol was not associated with increased breast cancer risk, yet other studies have not seen this interactive effect between dietary folate and alcohol intake (28,29). It seems that among women who consume alcohol, reducing alcohol consumption could potentially help to reduce their risk of breast cancer. SMOKING Whether smoking has an effect on breast cancer risk has been quite controversial. Smoking has been associated with lower circulating estrogens and earlier age at menopause, two

Section I Oncology and Oncoplastic Surgery

exposures that might reduce the risk of breast cancer. In light of the inconsistent ndings, some have asked whether exposure must occur early in a womans life, perhaps prior to her rst pregnancy, to have an impact. The analysis in the California Teachers Study found an increased hazard ratio of 1.32 (95% CI 1.10 to 1.57) for current smokers compared to never smokers (30). In addition to active smoking, many consider passive smoking to be just as potentially harmful. Analysis of the Million Womens Study and a meta-analysis found no association between passive smoking and breast cancer risk (31). The reanalysis of the data from the 53 epidemiologic studies indicated that smoking was associated with breast cancer but only among those who consumed alcohol (25). Most likely, both active and/or passive smoking are associated with increased risk of breast cancer for some women. We do not understand which women are susceptible to having smoking increase their risk of breast cancer. Smoking is associated with a multitude of other health risks, so there is no reason for a physician to wait to learn about breast cancer risk to counsel all patients regarding the need to quit smoking. BODY MASS INDEX In a pooled analysis of seven prospective cohort studies height was signicantly associated with breast cancer risk, with an RR of 1.07 (95% CI 1.03 to 1.12) for a change in 5 cm of height in postmenopausal women (32) but not as strongly associated for premenopausal women. Likewise the association with body mass index (BMI, weight/height2 in kg/m2) differed for premenopausal women and postmenopausal women. Among premenopausal women compared to a BMI of 21, women with a BMI of 31 had a RR of 0.54 (95% CI 0.34 to 0.85), while among postmenopausal women higher BMI was associated with increased risk of breast cancer (32). Among postmenopausal women body fat is the major source of circulating hormones through aromatization. In a study of circulating hormone levels, BMI was positively associated with estrone, estradiol, free testosterone, and prolactin and negatively associated with sex hormonebinding globulin (SHBG) (33). In a study that combined data on BMI and circulating hormone levels, the combined data from eight prospective studies suggested that the increased risk associated with increased BMI for postmenopausal breast cancer is explained through increased circulating sex hormone levels (34). Weight and BMI are potentially the most modiable breast cancer risk factors. However, most women typically gain weight during menopause as they become older. An analysis within the Nurses Health Study of 4,393 cases of invasive breast cancer compared to women who maintained their weight as an adult, the women who gained 25.0 kg or more were at increased risk, with a RR of 1.45 (95% CI 1.27 to 1.66) (35). More important, the women who lost weight after menopause were at lower risk than those who maintained the same weight, with a RR of 0.43 (95% CI 0.21 to 0.86) (35). Thus the reduction in breast cancer risk is one more reason to promote maintaining a healthy weight throughout adulthood. PHYSICAL ACTIVITY One of the most successful methods to maintain a healthy weight is through increased physical activity. While lower BMI levels had the biggest impact on circulating hormone levels, higher physical activity levels further reduced the circulating

hormone levels, suggesting an added benefit to increasing physical activity beyond just reducing BMI (33). One question is whether there is any added benefit to long-term vigorous physical activity. In an analysis of the California Teachers Study, breast cancer risk was inversely associated with long-term strenuous activity (36). The benet of vigorous physical activity was also seen in an analysis of the Breast Cancer Detection Demonstration Project Follow-up Study, with relative risk of 0.87 (95% CI 0.74 to 1.02), where nonvigorous activity showed no relation to breast cancer (37). Biologically, physical activity may change breast cancer risk pathways and have an impact on breast cancer risk beyond the reduction in BMI (38). BENIGN BREAST DISEASE Women with benign lesions of the breast are at increased risk of developing breast cancer over the next 10 years (39). In a study of the Mayo Clinic Benign Breast Disease cohort, benign breast lesions were classied based on the histology as nonproliferative lesions (67%), proliferative lesions without atypia (30%), and atypical hyperplasia (4%). These benign lesions are considered general markers of risk rather than precursor lesions in that the probability of developing contralateral breast cancer was the same as for ipsilateral disease after each lesion (40,41). BREAST DENSITY Breast density is one of the strongest breast cancer risk factors. Women with greater than 75% of their breast comprised of dense tissue have a fourfold to sixfold increased risk compared to women with very low breast density (42). Although it is a hormonal response condition, breast density appears to be independent of other risk factors (43). In a study of postmenopausal women within the Nurses Health Study, being in the highest quartile compared to the lowest was associated with a RR of 3.8 (95% CI 2.2 to 6.6) In postmenopausal women the increased risk associated with increased breast density was not explained by circulating hormones (43). From twin studies breast density appears to have a strong genetic component as well as environmental inuences (44). Breast density may increase breast cancer risk through a combination of cell proliferation and potential damage to these proliferating cells by mutagens (45). As an intermediate marker of breast cancer risk, breast density can help in the understanding of disease pathways as a marker of susceptibility (45). ENDOGENOUS HORMONES Clearly, ovarian hormones play a strong role in inuencing breast cancer risk. Two breast cancer risk factors that reect the hormonal patterns of risk are (1) early menopause, which reduces risk, and (2) postmenopausal obesity, which increases risk hormones (46). The log-log plot of age-specic incidence rates for breast cancer shows the change in breast cancer rates with menopause. It is these circulating hormone levels that can partially explain the association between BMI and postmenopausal breast cancer risk. The increased risk with higher BMI is associated with a concurrent increase in circulating estrogens and in particular with bioavailable estradiol (34). In a pooling analysis from nine prospective studies, the association between endogenous sex hormones and breast cancer (47) was clear. Breast cancer risk increased with increasing concentration

Chapter 1 The Epidemiology of Breast Cancer

of all sex hormones including estradiol, free estradiol, and SHBG. The RR values for women with increasing quintiles of estradiol were 1.42 (95% CI 1.04 to 1.95), 1.21 (95% CI 0.89 to 1.66), 1.80 (95% CI 1.33 to 2.43), and 2.00 (95% CI 1.47 to 2.71). The levels of endogenous sex hormones are strongly associated with breast cancer risk. This association between serum steroid levels and cancer risk persists for both premenopausal and postmenopausal women. Premenopausal women were at a 2.1-fold (95% CI 1.1 to 4.1) increased risk for high free estradiol levels (48). Likewise, postmenopausal circulating serum levels were strongly related to breast cancer risk (49). GROWTH FACTORS In addition to steroid hormones, other factors are associated with breast cancer risk. Plasma prolactin levels are associated with a RR of 1.93 (95% CI 1.16 to 3.22) for postmenopausal breast cancer (50). In contrast, IGF-1 has been shown to be associated with premenopausal breast cancer risk but not postmenopausal risk (51). Understanding the associations between circulating levels and breast cancer risk can help with both developing predictive models of breast cancer and understanding the disease process. EXOGENOUS HORMONES

dence has increased approximately 1% per year, with the most dramatic increase occurring in the 1980s and 1990s (55). The rapid decline in the incidence of breast cancer that occurred after the results of the Womens Health Initiative were published was quite dramatic. Breast cancer incidence from 1980 to 2006 resulted from the combined effects of postmenopausal hormone (PMH) use and screening mammography (56). Since PMH was used predominantly by White, educated urban dwellers (5759) and postmenopausal women and was associated with estrogenreceptor positive (ER) breast cancer, it t the rapid decline in use by this age group. Since most of the changes were expected to occur in older women undergoing routine screening, it was noted that the recent trends in breast cancer among younger women (40 years) were not greatly attributable to changes in PMH or mammography use (3). These rapid changes in disease incidence have been the source of much research to explain them (6065). After all the analyses it appears that the use of postmenopausal hormones had played a major role in increasing the incidence of breast cancer.

PREVENTION TRIALS: TAMOXIFEN AND STUDY OF TAMOXIFEN AND RALOXIFENE TRIALS


The initial breast cancer prevention trial compared tamoxifen to a placebo. Tamoxifen was found to provide a significant improvement and a reduction in breast cancer risk (66). However, use of tamoxifen also had potential side effects, and it was not that well accepted as a prevention drug to treat healthy atrisk women. The second prevention trialthe National Surgical Adjuvant Breast and Bowel Project P2 (Study of Tamoxifen and Raloxifene [STAR]) trialcompared raloxifene to tamoxifen in a randomized trial. Raloxifene was found to be as effective as tamoxifen in reducing the risk of invasive breast cancer and had a lower rate of side effects. These treatments were shown to be effective in preventing breast cancer cases overall and also for women with benign breast conditions or with family history and other risk markers (67,68).

Oral Contraceptives
A reanalysis of the data from 54 studies combined indicates that currently using oral contraceptives and being within 10 years after stopping use are associated with a small increase in the relative risk, with current use associated with a 24% increase (95% CI 1.15 to 1.33). There is no indication of an increase after 10 years after stopping use (52).

Postmenopausal Hormone Use: Estrogen Alone, Estrogen Plus Progesterone


In a reanalysis of data from 51 studies breast cancer risk increased by 1.023 (95% CI 1.011 to 1.036) for current and recent postmenopausal hormone use (53). These are similar results to many previous observational studies of postmenopausal hormone use and breast cancer risk. However, given the previously reported favorable associations with heart disease and other conditions in the Womens Health Initiative, a randomized trail was conducted to evaluate hormone replacement on multiple outcomes (54). Women were randomized to estrogens plus progesterone or a placebo. If the participants had previously had a hysterectomy, they were randomized to estrogen only or placebo. The estrogen plus progesterone arm of the study was closed early due to the high number of events with this treatment: not only increased breast cancer risk, but also other conditions as well.

GENETIC STUDIES
Great strides are being made in the study of genetics and breast cancer risk. The BRCA1 and BRCAII genes have been identied and have provided researchers a greater understanding of breast cancer risk. They have been studied to understand their role in signaling in DNA repair pathways (69). In addition to the highly penetrant BRCAI and BRACII genes, recent genome-wide association studies (GWAS) have identified a number of other signicant but lower-risk genes. GWAS have found that four of ve loci have plausible causative genes (FGFR2, TNRC9, MAP3K1, LSP1) (70). In addition, researchers have also evaluated whether these genes might better predict such associated breast cancer risk factors as age at menarche and natural menopause (71) Another GWAS study showed alleles of FGFR2 associated with postmenopausal breast cancer (72). Risk associated with GWAS-identied genes is modest, and one should emphasize the need to recognize gene environment interactions and not presume that everything is gene determined (73).

CHANGING INCIDENCE OF BREAST CANCER


Freuer and Wun (1992) had modeled the change in breast cancer risk and attributed some of the increase and subsequent slight decline to the use of mammography and screening in the 1980s and early 1990s (55). Since the 1940s, breast cancer inci-

Section I Oncology and Oncoplastic Surgery

RISK MODELS OF BREAST CANCER RISK


A number of models were developed to estimate the probability that an individual would be a gene mutation carrier for the BRCAI and BRACII genes (74,75). However, most women do not carry the highly penetrant gene mutations and are more likely to develop a sporadic case. The Gail model and its adaptations have been used extensively both to counsel women to understand their risk and for entry criteria for randomized trials such as the tamoxifen and STAR trials. While the Gail model is fairly simple and straightforward, the initial model lacks information on a number of very important risk factors such as breast density. Chen et al. developed a new model that incorporates breast density into a Gail-type risk model (76). Others also have developed models that incorporate breast density to predict individualized risk (77). While these models claim to provide individualized risk, these are still group-based models and tend to work well at predicting the events within a group, but the concordance for individuals is not that high. Gail also adapted his original model to better fit risk prediction in African American populations (78). In evaluating the Gail model against the WHI Observational Study, the model did very well at predicting ER breast cancer but not so well for ER disease (79). These models are works in progress, and new efforts need to be made to improve them (80). Others have proposed that we have sufcient information at this point to begin to use this information in practice. At least for postmenopausal women, a discussion of risk factors and breast density could allow for the discussion of chemoprevention agents if an individual was found to be at sufciently high risk (81).

plications for study design and sample population. In addition to the benets of studying the subtypes of breast cancer cases, there are challenges that we must face (99). By building on established knowledge of existing breast cancer risk factors and integrating new technologies and methods, we will continue to expand our understanding of breast cancer etiology.

EDITORIAL COMMENTS The mention of breast cancer evokes an emotional response. It is the most common malignancy in women and involves an organ that is the symbol of femininity. The majority of people have been touched by breast cancer in some way through family members or friends. Therefore, its incidence and risk factors are of intense interest. Risk for breast cancer seems to be multifactorial, and the epidemiologic study is difcult since the factors increasing risk may have been exerted on the developing breast with actual disease developing many decades later. This chapter illustrates the complexity of breast cancer risk assessment. Many of the risk factors for developing breast cancer are outside of the patients controlgenetics, family history, menstrual history, age of parturition, and breast density. Patients, especially at the time of diagnosis, question what they did to get breast cancer and similarly ask what they can do to improve their prognosis. Some risk factors can be modied, such as decreasing alcohol intake, maintaining a normal body weight, and exercising, although no single action or factor can be relied upon to prevent breast cancer. The risk for breast cancer is a continuum, and one of the challenges of dealing with patients is counseling them about where they fall on that continuum. As Dr. Byrne points out, many of the models that exist are population based and do not accurately predict risk at an individual level. Surveillance in these high-risk groups is challenging, and although it is fairly reliable, it is not foolproof. Unfortunately, there are common examples of later-stage disease diagnosed in women who had undergone intense surveillance. Improvement in both individual risk assessment and surveillance would have a favorable outcome on patient outcomes. The decision making about preventive measures is difcult. Acceptance of chemoprevention with tamoxifen or raloxifene by healthy high-risk individuals has not been high. Many patients initiate the discussion about bilateral prophylactic mastectomy and ultimately elect to have surgery, especially if they have seen a loved one die of breast cancer. It seems a drastic measure, but for the patient who has been counseled about the continued small but real risk of developing breast cancer, if given time to make her own decision and if she is fully informed about her reconstruction options, acceptance and satisfaction are high. S.C.W.

HETEROGENEITY OF BREAST CANCER


A major concern is that we quite often treat all breast cancers as one disease rather than look at different subtypes. Breast cancers that are classied by estrogen (ER) and progesterone receptor (PR) status present differently clinically and pathologically with different molecular features (82). Reproductive factors, alcohol intake, and postmenopausal obesity seem to be associated with ER breast cancer rather than the ER type (8387). A metaanalysis of multiple studies showed that BMI is associated with ER/PR breast cancer but not ER/PR breast cancers (88). In the Nurses Health Study, breast cancer risk factors vary by ER/PR status for age, menopause status, BMI after menopause, rst pregnancy effect, past use of PMH but not for benign breast disease, family history of breast cancer, alcohol use, and height (89). In addition to the ER/PR status, the cancer cases can be classied based on different patterns of histology (9092). Triple-negative breast cancers differ across racial groups and are found more often in younger, non-Hispanic Blacks and Hispanics (93,94). The age distributions of cases are different by ER/PR status and by histology (9597), as well as differences by racial groups (93). During the 1990s the rates of inammatory breast cancer rose, while survival declined slightly (98). Future research needs to better classify breast cancer subtypes into more homogeneous categories. In studies that do not consider subtypes of cases, differences in results could be due to different distributions of the subpopulations. As we make better use of new technologies we will help to better dene the disease and allow for a better understanding of the etiology. In doing these more directed studies we will need to also consider the im-

REFERENCES
1. Jemal A, Siegel R, Ward E, et al. Cancer statistics, 2009. CA Cancer J Clin 2009;59:225249. 2. Ries LAG, Melbert D, Krapcho M, et al., eds. SEER Cancer Statistics Review, 19752005. Bethesda, MD: National Cancer Institute; 2008. 3. Brinton LA, Sherman ME, Carreon JD, et al. Recent trends in breast cancer among younger women in the United States. J Natl Cancer Inst 2008;100:16431648. 4. Anderson WF, Rosenberg PS, Menashe I, et al. Age-related crossover in breast cancer incidence rates between Black and White ethnic groups. J Natl Cancer Inst 2008;100:18041814.

Chapter 1 The Epidemiology of Breast Cancer


5. Troisi R, Potischman N, Hoover RN. Exploring the underlying hormonal mechanisms of prenatal risk factors for breast cancer: a review and commentary. Cancer Epidemiol Biomarkers Prev 2007;16:17001712. 6. Ruder EH, Dorgan JF, Kranz S, et al. Examining breast cancer growth and lifestyle risk factors: early life, childhood, and adolescence. Clin Breast Cancer 2008;8:334342. 7. Troisi R, Hatch EE, Titus-Ernstoff L, et al. Birth weight and breast cancer risk. Br J Cancer 2006;94:17341737. 8. Xue F, Michels KB. Intrauterine factors and risk of breast cancer: a systematic review and meta-analysis of current evidence. Lancet Oncol 2007;8:10881100. 9. Troisi R, Innes KE, Roberts JM, et al. Preeclampsia and maternal breast cancer risk by offspring gender: do elevated androgen concentrations play a role? Br J Cancer 2007;97:688690. 10. Kelsey JL, Gammon MD, John EM. Reproductive factors and breast cancer. Epidemiol Rev 1993;15:3647. 11. Lacey JV Jr, Kreimer AR, Buys SS, et al. Breast cancer epidemiology according to recognized breast cancer risk factors in the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial Cohort. BMC Cancer 2009;9:84. 12. Nichols HB, Trentham-Dietz A, Hampton JM, et al. From menarche to menopause: trends among US women born from 1912 to 1969. Am J Epidemiol 2006;164:10031011. 13. White E. Projected changes in breast cancer incidence due to the trend toward delayed childbearing. Am J Public Health 1987;77:495497. 14. Pike MC, Krailo MD, Henderson BE, et al. Hormonal risk factors, breast tissue age and the age-incidence of breast cancer. Nature.1983;303:767770. 15. Kauppila A, Kyyronen P, Hinkula M, et al. Birth intervals and breast cancer risk. Br J Cancer 2009;101:12131217. 16. Beral V, Bull D, Doll R, et al. Breast cancer and abortion: collaborative reanalysis of data from 53 epidemiological studies, including 83,000 women with breast cancer from 16 countries. Lancet 2004;363:10071016. 17. Palmer JR, Wise LA, Horton NJ, et al. Dual effect of parity on breast cancer risk in AfricanAmerican women. J Natl Cancer Inst 2003;95:478483. 18. Collaborative Group on Hormonal Factors in Breast Cancer. Breast cancer and breastfeeding: collaborative reanalysis of individual data from 47 epidemiological studies in 30 countries, including 50302 women with breast cancer and 96973 women without the disease. Lancet 2002;360:187195. 19. Collaborative Group on Hormonal Factors in Breast Cancer. Familial breast cancer: collaborative reanalysis of individual data from 52 epidemiological studies including 58,209 women with breast cancer and 101,986 women without the disease. Lancet 2001;358: 13891399. 20. Ziegler RG, Hoover RN, Pike MC, et al. Migration patterns and breast cancer risk in AsianAmerican women. J Natl Cancer Inst 1993;85:18191827. 21. Smith-Warner SA, Spiegelman D, Adami HO, et al. Types of dietary fat and breast cancer: a pooled analysis of cohort studies. Int J Cancer 2001;92:767774. 22. Thiebaut AC, Kipnis V, Chang SC, et al. Dietary fat and postmenopausal invasive breast cancer in the National Institutes of Health-AARP Diet and Health Study cohort. J Natl Cancer Inst 2007;99:451462. 23. Smith-Warner SA, Stampfer MJ. Fat intake and breast cancer revisited. J Natl Cancer Inst 2007;99:418419. 24. Smith-Warner SA, Spiegelman D, Yaun SS, et al. Alcohol and breast cancer in women: a pooled analysis of cohort studies. JAMA 1998;279:535540. 25. Hamajima N, Hirose K, Tajima K, et al. Alcohol, tobacco and breast cancercollaborative reanalysis of individual data from 53 epidemiological studies, including 58,515 women with breast cancer and 95,067 women without the disease. Br J Cancer 2002;87:12341245. 26. Dumitrescu RG, Shields PG. The etiology of alcohol-induced breast cancer. Alcohol 2005;35:213225. 27. Zhang S, Hunter DJ, Hankinson SE, et al. A prospective study of folate intake and the risk of breast cancer. JAMA 1999;281:16321637. 28. Duffy CM, Assaf A, Cyr M, et al. Alcohol and folate intake and breast cancer risk in the WHI Observational Study. Breast Cancer Res Treat 2009;116:551562. 29. Tjonneland A, Christensen J, Olsen A, et al. Alcohol intake and breast cancer risk: the European Prospective Investigation into Cancer and Nutrition (EPIC). Cancer Causes Control 2007;18:361373. 30. Reynolds P, Hurley S, Goldberg DE, et al. Active smoking, household passive smoking, and breast cancer: evidence from the California Teachers Study. J Natl Cancer Inst 2004;96: 2937. 31. Pirie K, Beral V, Peto R, et al. Passive smoking and breast cancer in never smokers: prospective study and meta-analysis. Int J Epidemiol 2008;37:10691079. 32. van den Brandt PA, Spiegelman D, Yaun SS, et al. Pooled analysis of prospective cohort studies on height, weight, and breast cancer risk. Am J Epidemiol 2000;152:514527. 33. McTiernan A, Wu L, Chen C, et al. Relation of BMI and physical activity to sex hormones in postmenopausal women. Obesity (Silver Spring) 2006;14:16621677. 34. Key TJ, Appleby PN, Reeves GK, et al. Body mass index, serum sex hormones, and breast cancer risk in postmenopausal women. J Natl Cancer Inst 2003;95:12181226. 35. Eliassen AH, Colditz GA, Rosner B, et al. Adult weight change and risk of postmenopausal breast cancer. JAMA 2006;296:193201. 36. Dallal CM, Sullivan-Halley J, Ross RK, et al. Long-term recreational physical activity and risk of invasive and in situ breast cancer: the California teachers study. Arch Intern Med 2007;167:408415. 37. Leitzmann MF, Moore SC, Peters TM, et al. Prospective study of physical activity and risk of postmenopausal breast cancer. Breast Cancer Res 2008;10:R92. 38. Neilson HK, Friedenreich CM, Brockton NT, et al. Physical activity and postmenopausal breast cancer: proposed biologic mechanisms and areas for future research. Cancer Epidemiol Biomarkers Prev 2009;18:1127. 39. Hartmann LC, Sellers TA, Frost MH, et al. Benign breast disease and the risk of breast cancer. N Engl J Med 2005;353:229237. 40. Cook MG, Rohan TE. Benign breast disease: the relationship between its histological features and risk factors for breast cancer. Pathology 1991;23:286290.

41. Hartmann LC, Ghosh K. Benign breast disease: emerging ndings in a diverse population. Breast J 2007;13:113114. 42. Byrne C, Schairer C, Wolfe J, et al. Mammographic features and breast cancer risk: effects with time, age, and menopause status. J Natl Cancer Inst 1995;87:16221629. 43. Tamimi RM, Byrne C, Colditz GA, et al. Endogenous hormone levels, mammographic density, and subsequent risk of breast cancer in postmenopausal women. J Natl Cancer Inst 2007;99:11781187. 44. Boyd NF, Dite GS, Stone J, et al. Heritability of mammographic density, a risk factor for breast cancer. N Engl J Med 2002;347:886894. 45. Martin LJ, Boyd NF. Mammographic density. Potential mechanisms of breast cancer risk associated with mammographic density: hypotheses based on epidemiological evidence. Breast Cancer Res 2008;10:201. 46. Pike MC, Spicer DV, Dahmoush L, et al. Estrogens, progestogens, normal breast cell proliferation, and breast cancer risk. Epidemiol Rev 1993;15:1735. 47. Key T, Appleby P, Barnes I, et al. Endogenous sex hormones and breast cancer in postmenopausal women: reanalysis of nine prospective studies. J Natl Cancer Inst 2002;94: 606616. 48. Eliassen AH, Missmer SA, Tworoger SS, et al. Endogenous steroid hormone concentrations and risk of breast cancer among premenopausal women. J Natl Cancer Inst 2006;98: 14061415. 49. Missmer SA, Eliassen AH, Barbieri RL, et al. Endogenous estrogen, androgen, and progesterone concentrations and breast cancer risk among postmenopausal women. J Natl Cancer Inst 2004;96:18561865. 50. Hankinson SE, Willett WC, Michaud DS, et al. Plasma prolactin levels and subsequent risk of breast cancer in postmenopausal women. J Natl Cancer Inst 1999;91:629634. 51. Schernhammer ES, Holly JM, Pollak MN, et al. Circulating levels of insulin-like growth factors, their binding proteins, and breast cancer risk. Cancer Epidemiol Biomarkers Prev 2005;14:699704. 52. Breast cancer and hormonal contraceptives: collaborative reanalysis of individual data on 53 297 women with breast cancer and 100 239 women without breast cancer from 54 epidemiological studies. Collaborative Group on Hormonal Factors in Breast Cancer. Lancet 1996;347:17131727. 53. Breast cancer and hormone replacement therapy: collaborative reanalysis of data from 51 epidemiological studies of 52,705 women with breast cancer and 108,411 women without breast cancer. Collaborative Group on Hormonal Factors in Breast Cancer. Lancet 1997;350:10471059. 54. Rossouw JE, Anderson GL, Prentice RL, et al. Risks and benets of estrogen plus progestin in healthy postmenopausal women: principal results from the Womens Health Initiative randomized controlled trial. JAMA 2002;288:321333. 55. Feuer EJ, Wun LM. How much of the recent rise in breast cancer incidence can be explained by increases in mammography utilization? A dynamic population model approach. Am J Epidemiol 1992;136:14231436. 56. Glass AG, Lacey JV Jr, Carreon JD, et al. Breast cancer incidence, 19802006: combined roles of menopausal hormone therapy, screening mammography, and estrogen receptor status. J Natl Cancer Inst 2007;99:11521161. 57. Hausauer AK, Keegan TH, Chang ET, et al. Recent trends in breast cancer incidence in US White women by county-level urban/rural and poverty status. BMC Med 2009;7:31. 58. Jemal A, Ward E, Thun MJ. Recent trends in breast cancer incidence rates by age and tumor characteristics among U.S. women. Breast Cancer Res 2007;9:R28. 59. Hausauer AK, Keegan TH, Chang ET, et al. Recent breast cancer trends among Asian/Pacic Islander, Hispanic, and African-American women in the US: changes by tumor subtype. Breast Cancer Res 2007;9:R90. 60. Smigal C, Jemal A, Ward E, et al. Trends in breast cancer by race and ethnicity: update 2006. CA Cancer J Clin 2006;56:168183. 61. Zheng T, Holford TR, Chen Y, et al. Time trend of female breast carcinoma in situ by race and histology in Connecticut, USA. Eur J Cancer 1997;33:96100. 62. Eheman CR, Shaw KM, Ryerson AB, et al. The changing incidence of in situ and invasive ductal and lobular breast carcinomas: United States, 19992004. Cancer Epidemiol Biomarkers Prev 2009;18:17631769. 63. Ravdin PM, Cronin KA, Howlader N, et al. The decrease in breast-cancer incidence in 2003 in the United States. N Engl J Med 2007;356:16701674. 64. Berry DA, Ravdin PM. Breast cancer trends: a marriage between clinical trial evidence and epidemiology. J Natl Cancer Inst 2007;99:11391141. 65. Verkooijen HM, Bouchardy C, Vinh-Hung V, et al. The incidence of breast cancer and changes in the use of hormone replacement therapy: a review of the evidence. Maturitas 2009;64:8085. 66. Fisher B, Costantino JP, Wickerham DL, et al. Tamoxifen for prevention of breast cancer: report of the National Surgical Adjuvant Breast and Bowel Project P-1 Study. J Natl Cancer Inst 1998;90:13711388. 67. Vogel VG, Costantino JP, Wickerham DL, et al. Effects of tamoxifen vs raloxifene on the risk of developing invasive breast cancer and other disease outcomes: the NSABP Study of Tamoxifen and Raloxifene (STAR) P-2 trial. JAMA 2006;295:27272741. 68. Wickerham DL, Costantino JP, Vogel VG, et al. The use of tamoxifen and raloxifene for the prevention of breast cancer. Recent Results Cancer Res 2009;181:113119. 69. Begg CB, Haile RW, Borg A, et al. Variation of breast cancer risk among BRCA1/2 carriers. JAMA 2008;299:194201. 70. Easton DF, Pooley KA, Dunning AM, et al. Genome-wide association study identies novel breast cancer susceptibility loci. Nature 2007;447:10871093. 71. He C, Kraft P, Chen C, et al. Genome-wide association studies identify loci associated with age at menarche and age at natural menopause Nat Genet 2009;41:724728. 72. Hunter DJ, Kraft P, Jacobs KB, et al. A genome-wide association study identies alleles in FGFR2 associated with risk of sporadic postmenopausal breast cancer. Nat Genet 2007;39: 870874. 73. Ambrosone CB. The promise and limitations of genome-wide association studies to elucidate the causes of breast cancer. Breast Cancer Res 2007;9:114.

10

Section I Oncology and Oncoplastic Surgery


87. Chu KC, Anderson WF. Rates for breast cancer characteristics by estrogen and progesterone receptor status in the major racial/ethnic groups. Breast Cancer Res Treat 2002;74:199211. 88. Suzuki R, Orsini N, Saji S, et al. Body weight and incidence of breast cancer dened by estrogen and progesterone receptor statusa meta-analysis. Int J Cancer 2009;124:698712. 89. Colditz GA, Rosner BA, Chen WY, et al. Risk factors for breast cancer according to estrogen and progesterone receptor status. J Natl Cancer Inst 2004;96:218228. 90. Reeves GK, Beral V, Green J, et al. Hormonal therapy for menopause and breast-cancer risk by histological type: a cohort study and meta-analysis. Lancet Oncol 2006;7:910918. 91. Couto E, Banks E, Reeves G, et al. Family history and breast cancer tumour characteristics in screened women. Int J Cancer 2008;123:29502954. 92. Phipps AI, Malone KE, Porter PL, et al. Body size and risk of luminal, HER2-overexpressing, and triple-negative breast cancer in postmenopausal women. Cancer Epidemiol Biomarkers Prev 2008;17:20782086. 93. Bauer KR, Brown M, Cress RD, et al. Descriptive analysis of estrogen receptor (ER)-negative, progesterone receptor (PR)-negative, and HER2-negative invasive breast cancer, the so-called triple-negative phenotype: a population-based study from the California Cancer Registry. Cancer 2007;109:17211728. 94. Trivers KF, Lund MJ, Porter PL, et al. The epidemiology of triple-negative breast cancer, including race. Cancer Causes Control 2009;20:10711082. 95. Anderson WF, Chu KC, Chang S, et al. Comparison of age-specic incidence rate patterns for different histopathologic types of breast carcinoma. Cancer Epidemiol Biomarkers Prev 2004;13:11281135. 96. Anderson WF, Pfeiffer RM, Dores GM, et al. Comparison of age distribution patterns for different histopathologic types of breast carcinoma. Cancer Epidemiol Biomarkers Prev 2006;15:18991905. 97. Reeves GK, Pirie K, Green J, et al. Reproductive factors and specic histological types of breast cancer: prospective study and meta-analysis. Br J Cancer 2009;100:538544. 98. Hance KW, Anderson WF, Devesa SS, et al. Trends in inammatory breast carcinoma incidence and survival: the surveillance, epidemiology, and end results program at the National Cancer Institute. J Natl Cancer Inst 2005;97:966975. 99. Troester MA, Swift-Scanlan T. Challenges in studying the etiology of breast cancer subtypes. Breast Cancer Res 2009;11:104.

74. Marroni F, Aretini P, DAndrea E, et al. Evaluation of widely used models for predicting BRCA1 and BRCA2 mutations. J Med Genet 2004;41:278285. 75. Parmigiani G, Chen S, Iversen ES Jr, et al. Validity of models for predicting BRCA1 and BRCA2 mutations. Ann Intern Med 2007;147:441450. 76. Chen J, Pee D, Ayyagari R, et al. Projecting absolute invasive breast cancer risk in White women with a model that includes mammographic density. J Natl Cancer Inst 2006;98:12151226. 77. Tice JA, Cummings SR, Ziv E, et al. Mammographic breast density and the Gail model for breast cancer risk prediction in a screening population. Breast Cancer Res Treat 2005;94:115122. 78. Gail MH, Costantino JP, Pee D, et al. Projecting individualized absolute invasive breast cancer risk in African American women. J Natl Cancer Inst 2007;99:17821792. 79. Chlebowski RT, Anderson GL, Lane DS, et al. Predicting risk of breast cancer in postmenopausal women by hormone receptor status. J Natl Cancer Inst 2007;99:16951705. 80. Santen RJ, Boyd NF, Chlebowski RT, et al. Critical assessment of new risk factors for breast cancer: considerations for development of an improved risk prediction model. Endocr Relat Cancer 2007;14:169187. 81. Cummings SR, Tice JA, Bauer S, et al. Prevention of breast cancer in postmenopausal women: approaches to estimating and reducing risk. J Natl Cancer Inst 2009;101:384398. 82. Rosenberg LU, Einarsdottir K, Friman EI, et al. Risk factors for hormone receptor-dened breast cancer in postmenopausal women. Cancer Epidemiol Biomarkers Prev 2006;15: 24822488. 83. Althuis MD, Fergenbaum JH, Garcia-Closas M, et al. Etiology of hormone receptor-dened breast cancer: a systematic review of the literature. Cancer Epidemiol Biomarkers Prev 2004;13: 15581568. 84. Ma H, Bernstein L, Pike MC, et al. Reproductive factors and breast cancer risk according to joint estrogen and progesterone receptor status: a meta-analysis of epidemiological studies. Breast Cancer Res 2006;8:R43. 85. Deandrea S, Talamini R, Foschi R, et al. Alcohol and breast cancer risk dened by estrogen and progesterone receptor status: a case-control study. Cancer Epidemiol Biomarkers Prev 2008;17:20252028. 86. Suzuki R, Orsini N, Mignone L, et al. Alcohol intake and risk of breast cancer dened by estrogen and progesterone receptor statusa meta-analysis of epidemiological studies. Int J Cancer 2008;122:18321841.

CHAPTER

2
In 2007 an estimated 178,480 new cases of invasive breast cancer and 62,030 cases of in situ breast cancer were expected to be diagnosed. A total of 40,460 women were expected to die from breast cancer in 2007; only lung cancer was expected to account for more deaths (1). Five-year survival is lower among women with a more advanced stage of disease. Five-year relative survival is 98% for localized disease, 84% for regional disease, and 27% for distant disease (1). Early detection is the most important determinant in reducing mortality from breast cancer. Regular screening is detecting more tumors, but too many are still being missed. The American Cancer Society has revised its breast cancer screening recommendations six times in the last 30 years as new information has become available (2). Until recently screen lm mammography has been the standard of care for screening. Other modalities, such as digital mammography, computer-aided detection (CAD), magnetic resonance imaging (MRI) and dedicated breast positron emission tomography are all adding to the arsenal of early detection, and their roles continue to be better dened. The American Cancer Society (ACS) guidelines for breast cancer screening currently recommend that for average-risk women mammographic screening begin at age 40 years. Women in their 20s and 30s should have a clinical breast exam every 3 years. Women over 40 years of age should have a clinical breast examination yearly. Women should be told about the benets and limitations of breast self-examination and the importance of prompt reporting of any new breast symptoms. As long as a woman is in reasonably good health and would be a candidate for treatment, she should continue to be screened with mammography. For women at high risk, earlier initiation of screening, shorter screening intervals, or the addition of other modalities may provide benet. An addendum was issued to these guidelines in 2007. It recommended annual MRI screening in addition to mammography for BRCA mutation carriers; rst-degree relatives of BRCA carriers who are untested and those patients with a calculated lifetime risk of 20% to 25% or greater as dened by BRCAPRO or other models that are largely dependent on family history. MRI is also recommended for patients who received radiation to their chest between age 10 and 30 years, patients with Li-Fraumeni syndrome and their rst-degree relatives, and patients with Cowden and Bannayan-Riley-Ruvalcaba syndromes and their rst-degree relatives (3).

Costanza Cocilovo

Breast Cancer Screening and Diagnosis


clinical and breast self-examination as a complement to breast cancer screening as well as self-awareness. Women who detect breast tumors themselves typically nd them outside of a structured examination, such as when bathing or getting dressed (4), so self-awareness is vital.

MAMMOGRAPHY
The historical evidence supporting the recommendation for screening mammography comes from eight randomized trials that were performed in Sweden, the United States, Canada, and the United Kingdom (4). Overall, breast cancers detected by screening mammography are smaller and have a more favorable history than those detected by clinical exam. A pooled analysis of the most recent data from all randomized trials of screening mammography in women aged 39 to 74 years showed a 24% reduction in mortality, although not all trials showed a statistically signicant mortality reduction (4). Historically the United States has differed from Canada and other European countries in their recommendations for the interval of screening and the recommendations for the oldest and youngest women. In 2008 the National Health Service Breast Screening Program (NHSBP) in the United Kingdom issued an update on its 20-year anniversary. Although based on data showing that the best screening interval is likely 18 months to 2 years, based on cost-benet study the U.K. program decided to offer screening every 3 years. In the United States women are encouraged to have a yearly mammogram starting at age 40 years, although given that 80% of breast cancers occur in women over 50 years, there is a minimal survival benet to screening women under the age of 50 years. Screening the 40- to 49 year age group leads to 0.8 death avoided per 1,000. The NHSBSP encourages these younger women to understand the limitations of screening this age population and notes that private facilities do offer the service (5). The Canadian health service similarly reviewed their results, and their nal recommendation was that women in the 40- to 49-year age group should be told the risks and benets and allowed to decide for themselves when they wish to start screening (6). A review from the Cleveland Clinic stated that, based on meta-analysis, screening women in their 40s decreases breast cancer death rates by about 20% (7). The guidelines in the United States indicate to start screening at age 40 years in the average-risk woman. Life expectancy continues to increase, and in developed countries women aged 75 years and older represent an increasing percentage of the population (8). Evidence-based guidelines for the regular screening of older women are lacking. Based on review of the literature, the authors found a consistent higher risk of death from breast cancer among nonusers compared to regular users of screening mammograms in the 75- to 84-year age group. This was also seen in the 85 years age group, although it was not statistically signicant. Patients

BREAST SELF-EXAMINATION
The U.S. Preventive Services Task Force takes the stance that there is insufficient evidence to recommend for or against breast cancer screening with clinical breast examination alone (4). As stated earlier, the ACS guidelines do recommend regular clinical breast examinations. Given that 10% to 15% of breast cancers are mammographically occult, there is a role for

11

12

Section I Oncology and Oncoplastic Surgery

with life expectancies less than 5 years are not likely to derive any survival benet from cancer screening (8). Age in itself should not be a reason to stop screening but rather the patients overall health and ability to receive treatment and benet from the screening. DIGITAL MAMMOGRAPHY Breast cancer screening is less effective in younger women than in older women, most likely because younger women have a higher proportion of mammographically dense breast tissue. Digital mammography addresses some of the problems seen with regular lm screen mammography. It has a wider range of contrast resolution, improving the detection of low-contrast lesions in radiographically dense breasts. It allows for the use of computer-aided detection and allows for electronic transmission, storage, and retrieval of images. The Digital Mammography Imaging and Screening Trial (DMIST), a large multicenter trial funded by the National Cancer Institute, was designed to address many deficiencies of prior studies. Prior studies demonstrated no benet to digital mammography. A total of 49,528 women were enrolled from 33 practices in the United States and Canada. The performance of digital mammography was signicantly better than lm mammography for women under the age of 50 years, women with heterogeneously dense or extremely dense breasts, and women not yet menopausal. The sensitivity was signicantly higher. Recall rates and biopsy rates were similar for the two modalities (9). As with all technologies, there was a learning curve in the interpretation of digital images, and that is likely why earlier trials did not show the benet that DMIST later showed. COMPUTER-AIDED DETECTION The false-negative rate for mammography has been reported to be between 10% and 30%. Although many cancers are mammographically occult, especially in dense breasts, the largest portion of false-negative cancers are visible in retrospect. These cancers are overlooked or not perceived as worrisome. Blinded reviews of prior mammograms showed that 25% to 41% of cancers seen with screening mammography could be seen retrospectively (10). Sensitivity can be improved by 4.6% to 15% when two radiologists are used instead of one (11). Cancers detected through double reading are detected at an earlier stage of development. However, the additional costs incurred from double reading are prohibitive. The CAD program identies potential abnormalities on the images and marks areas on the study that the computer considers to be suspicious. The radiologist reviews the agged areas to ensure that nothing was missed. Digital mammography provides images that can be used with CAD (10). The use of CAD has resulted in a 19.5% increase in cancer detection from 3.2 to 3.8 cancers per 1,000 in a high-volume screening study of about 13,000 women (12). CAD had the greatest effect on ductal carcinoma in situ (DCIS) by increasing detection by 14.2%. CAD resulted in a decrease in biopsy rate with a nonsignicant increase in positive predictive value of 26.3% from 21.9% (10). CAD correctly agged 84% of masses, 98% of microcalcication cases, and 89% of mixed mass/microcalcication lesions (13). Numerous studies have shown the positive effects of CAD on breast cancer detection rates. CAD does not seem to increase recall rates. It has the greatest potential impact on nding microcalcications, partic-

ularly in dense breasts. As CAD can have false-negative results, a suspicious area on mammogram should not preclude a diagnostic workup if it is not picked up on CAD (10).

SONOGRAPHY
Ultrasound uses high-frequency sound waves to create a picture of an area of interest. As there is no ionizing radiation, it is useful in young and pregnant women. Ultrasound is able to look at only a small area of the breast at a time and it is very operator and patient dependent (4). Ultrasound is generally not used as a screening device but can be used to evaluate palpable masses or mammographic and MRI-detected lesions. Ultrasound may increase the sensitivity of screening if it is used as an adjunct to mammography for women shown to have radiologically dense breasts, but it is likely to increase the number of women requiring biopsy for benign ndings (14). In general it is not a useful screening tool. In a single-institution review of new breast malignancies identied solely by ultrasound, a total of 34,694 breast sonograms were performed at an outpatient radiology afliate between April 1998 and April 2006. Of all cancers diagnosed, 2.2% were identied solely by sonography. The number of cancers identied relative to the total number of sonograms done was 0.03% (15). Given these numbers, ultrasound should be used selectively. Ultrasound is 96% to 100% sensitive in detecting breast cysts. Ultrasound is less effective in demonstrating solid masses. Bassett et al. found that only 63% of solid masses were visible on ultrasound (16). Breast ultrasound does not consistently detect microcalcications (17). If a palpable mass or asymmetry is not clinically suspicious, and the mammogram and ultrasound are both negative, the risk for cancer is low, but the possibility of cancer still exists. Diagnostic options then include either a biopsy or close observation. Ultrasound is a great adjunct to breast biopsy. It can guide ne needle aspiration (FNA), core biopsy, or placement of a localizing wire for an excisional biopsy more easily for both the patient and breast imager than can other imaging modalities.

MAGNETIC RESONANCE IMAGING


MRI produces images from a combination of a strong magnetic eld, radio waves, and computer processing. Every study on MRI has reported higher sensitivity than mammography, ultrasound, or both. Specicity of MRI tends to be lower than that of mammography (17). In a study of 1,909 women in the Netherlands the authors noted that screening MRI led to twice as many unneeded additional examinations and three times as many unneeded biopsies as did screening with mammography (18). Current research is focused on the suitability of MRI as a screening modality in conjunction with mammography in highrisk populations. The limitations of MRI include its high cost, unsuitability for some patients (those who are obese, have pacemakers, or have renal failure), the potential for unnecessary biopsies, lack of portability and the length of time required for imaging. The patient receives an intravenous line and is given gadolinium for contrast enhancement. Then 20 minutes of motionless scan time follows (4). There are three different patterns of dynamic enhancement. The type 1 pattern (persistent) shows slow, progressive contrast uptake over time and is suggestive of benignity. The type II contrast pattern (plateau)

Chapter 2 Breast Cancer Screening and Diagnosis

13

shows a rapid uptake in contrast and then a leveling off of uptake. This pattern is suggestive of malignancy. The type III pattern (washout) is indicative of malignancy (10). The diagnostic evaluation must also include the assessment of lesion morphology, which requires high-resolution imaging. The border of the lesion is the most important feature. Spiculated and irregular margins have a positive predictive value of malignancy ranging from 76% to 91%. Most benign masses have a smooth border with a negative predictive value for malignancy of 90% (10,19). DCIS is suggested by small, clumped foci that are within a segment or duct (20). MRI is often used to evaluate a patient with a new diagnosis of breast cancer. Multifocal and multicentric tumors are better imaged by MRI than by conventional methods (10). Additional sites of cancer were present on MRI in 19 (27%) of 70 women studied at Memorial Sloan-Kettering Cancer Center (21). At Memorial Sloan-Kettering, MRI detected contralateral breast cancer that was occult mammographically and by physical exam in 5% of women with a known breast cancer (21). The value of MRI in BRCA carriers has been shown. Occult cancers have been detected at a rate of 2% to 7% (10). The updated American Cancer Society guidelines are clear about the groups that should receive additional screening with MRI. They are less clear about some other high-risk groups. Memorial SloanKettering reviewed their experience with screening patients who had a diagnosis of atypia hyperplasia (AH) and lobular carcinoma in situ (LCIS). Their retrospective review had 378 patients; 126 had AH and 252 had LCIS. A total of 182 had screening MRIs. Those who had the MRIs were younger and had stronger family histories of breast cancer. Fifty-ve biopsies were recommended; 46 of these were based on MRI ndings alone. Cancer was detected in 6 of 46 (13%) of the MRI-generated biopsies. All six cancers were in patients with a diagnosis of LCIS. This was a highly selected group of patients, so it is difcult to conclude whether this should lead to MRI screening for all patients with LCIS (22). MRI appears very promising in screening highrisk patients and patients with a new diagnosis of breast cancer. However, the high false-positive rate leads to many benign biopsies. The role of MRI in breast cancer screening and diagnosis will continue to be evaluated and dened.

SCINTIMAMMOGRAPHY
Another form of breast imaging that involves the functional uptake of radiotracers is scintimammography. It uses 99Tcsestamibi, which is taken up by breast cancers. A dual-head machine was tested at the Mayo Clinic, which studied more than 900 patients in 6 years. The machine functions independent of breast density. Heavy compression of the breast is not required. They found a 97% concordance with mammography. Medicare charges are estimated at $1,029.69 for MRI and $292.12 for scintimammography. The nal sensitivity is over 90%, making this a useful adjunct to mammography (26). As these are emerging technologies that are not yet widely used, clinical data are still scarce.

DIAGNOSIS
Having found a lesion that is indeterminate or suspicious, there are various modalities available to obtain a diagnosis. If a lesion is felt to be cystic, then ultrasound should indicate if this is a simple or complex lesion. If it is a simple cyst, then FNA can be performed. Under ultrasound guidance FNA can prove that something is cystic while simultaneously treating it. If the uid is nonbloody, it can be discarded. If there is any doubt about the benign nature or if the uid appears bloody, it can be sent for cytologic examination. Most aspirations are performed in the ofce with a 22-gauge needle and a 10-cc syringe. If the mass is found to be solid, then under aspiration several passes can be made to dislodge and obtain cells. The suction is released, and the syringe is withdrawn. The sample is then placed on glass slides and in CytoLyt solution. Several series have compared cytologic results with histologic results (2736) (Table 2.1). Combined sensitivity was 93.3%, specicity was 96.6%, and accuracy was 94.7%. The false-negative rate was 6.7%, and the false-positive rate was 1.1%. Cytology cannot distinguish invasive from in situ carcinoma, but it can quickly provide a diagnosis of carcinoma. The false-negative rate of 6.7% is high enough that if a lesion is suspicious and cytology appears discordant, then a larger biopsy should be performed to rule out carcinoma. CORE BIOPSY Core biopsies are larger-needle biopsies. They are performed under ultrasound guidance or under mammographic guidance, called a stereotactic biopsy. They use different needle sizes, from 8 to 11 gauge. The biopsy is performed with local anesthesia through a small nick in the skin. The advantage of a core biopsy is that a small amount of tissue is removed intact, as opposed to FNA, which aspirates individual cells. The tissue can then be analyzed with various pathologic stains. In the case of breast, it can be tested for estrogen, progesterone, and Her2/neu positivity. In a study of 280 lesions found to be benign by stereotactic or ultrasound guided core biopsy, 15 (4.3%) were malignant at the time of excisional biopsy (37). Dahlstrom et al. found that of 116 lesions diagnosed as benign on stereotactic biopsy, 1 was malignant (38). There were no false-positive results in these series. This is important because often treatment is started on the basis of core biopsy results. A patient may begin neoadjuvant chemotherapy or plan for a cancer operation. Stereotactic core biopsy is performed for lesions, usually calcications that are seen only on mammogram. Stereotactic refers to how the lesion

NUCLEAR IMAGING
Most breast malignancies have greater metabolism than normal tissues and concentrate 18F-uorodeoxyglucose (FDG), the agent most widely used in clinical positron emission tomography (PET) scanning (6). Whole-body PET does not have the spatial resolution needed for breast imaging. PET/computed tomography has been shown to be useful in the restaging of breast cancer, in evaluation of response to therapy, and as a problem-solving method (23). Small, dedicated PET scanners have been developed for breast imaging, which use gentle compression. A pilot study of positron emission mammography (PEM) by Tafra et al. evaluated 44 images. PEM demonstrated 89% of the lesions. Multifocal disease was correctly ruled out in 17 of 17 cases (24). Berg et al. found that PEM combined with mammography and sonography yielded 47 (98%) of 48 cancers (25). Dense breasts do not appear to negatively affect PEM as they do mammography. Lower-grade tumors are more likely to be missed, which makes sense, as the technique employed in PEM is based on FDG concentration.

14

Section I Oncology and Oncoplastic Surgery

TABLE 2.1
Reference
Knight et al. (27) Smallwood et al. (35) Painter et al. (29) Smith et al. (30) Vetrani et al. (31) Zajdela et al. (28) Bell et al. (33) Kaufman et al. (34) Palombini et al. (32) Total

Correlation of FNA Cytology with Histologic Finding


Histologically Malignant
213 276 52 133 146 1,656 237 88 492 3,293

Histologically Benign
146 204 50 253 117 961 757 68 178 2,734

True Negative
137 204 49 238 110 916 615 68 178 2,734

False Positive
9 0 1 15 7 3 0 0 0 35

False Negative
41 15 4 8 5 63 27 2 15 180

is targeted, with a stereo pair of digital images. The patient is in the prone position with the breast through a hole in light compression. The biopsy unit is under the table with a computer that calculates the coordinates. The needle is vacuum assisted, and the specimen is pulled into a reservoir. A clip is then placed to mark the area. A mammogram is then performed to conrm removal of the area of interest and placement of the clip. A patient must be able to lie in the prone position and cooperate with the procedure, precluding some patients. A technical limitation is that, supercial and very posterior lesions are difcult to biopsy using this technique, as are lesions in very small breasts. Most tables also have a 300-pound weight limit (4). There is a very low rate of clinically signicant hematoma or infection after core biopsy. A follow-up mammogram or ultrasound should be performed 6 months after a benign biopsy to look for any suspicious ndings, such as an enlarging mass or increasing calcications. If the specimen shows atypia or is in any way considered discordant or inadequate, then a surgical biopsy should be performed. SURGICAL BIOPSY Standard of care is evolving, and whenever possible it is recommended that a diagnosis be obtained prior to the patient going to the operating room. However, surgical biopsies remain necessary when the location of the lesion is such that it cannot be biopsied using image-guided techniques, the core biopsy was in some way indeterminate or discordant, or the core biopsy showed a diagnosis such as atypia or papilloma that requires further tissue excision to be sure that a carcinoma was not missed. The majority of surgical biopsies are performed with local anesthetic and intravenous sedation. If possible, a circumareolar incision provides an excellent cosmetic outcome. If there is a chance of malignancy, tunneling should be avoided. One should consider both cosmetic outcome and, in the case of malignancy, the potential need for future mastectomy when choosing a site for the incision. Other than in the subareolar area, the underlying breast tissue should not be reapproximated because this results in more retraction. Since an open space is left behind, meticulous hemostasis should be obtained prior to closing the incision. Staples or external sutures should be avoided for optimal cosmesis. If malignancy is likely, the specimen should always be oriented so the location of any positive margin can be determined. Possible complications of a surgical biopsy include bleeding,

hematoma, ecchymosis, infection, numbness, paresthesia, and interference with breast-feeding. In the case of a biopsy performed with the guidance of needle localization the patient should be aware of the possibility of a missed lesion. The eld of breast cancer screening and diagnosis, like all others, continues to evolve. Better, earlier, and more complete diagnoses are possible due to improving technologies. This progress will certainly continue in the future, and with better imaging cancer will be diagnosed more precisely and at everearlier stages. The techniques for diagnosis will be less and less invasive and ever more precise. More often surgeons will be able to obtain a diagnosis preoperatively and carefully plan and execute their surgeries. We all look forward to continued progress while admiring how far we have already come.

EDITORIAL COMMENTS A public outcry greeted the recommendations in November 2009 of the US Preventive Services Task Force that recommended against screening mammograms in women 4049 and for biennial screening mammograms in women age 5074. They concluded that there is insufcient evidence to make recommendations about screening mammography in women older than 75, to assess the benets or harm of clinical breast exam, magnetic resonance imaging (MRI) and digital mammography. In addition, they recommended against teaching breast self-examination. The Task Force recommendations have been met with strong opposition by most professional organizations and did not effect a change in guidelines by organizations such as the American Cancer Society for screening mammography in average risk individuals. Although there is a strong recommendation to use MRI in gene mutation carriers, there remains controversy about the use of MRI in patients newly diagnosed with breast cancer and those with atypia and LCIS. New imaging modalities such as positron emission mammography and scintimammography pose exciting possibilities. The additional cost associated with these new imaging modalities may be prohibitive for our medical system and may never be cost-effective for screening large populations at

Chapter 2 Breast Cancer Screening and Diagnosis

15

average risk. It has been difcult to prove that screening mammography is cost effective and associated with decreased mortality in all age groups and proving the same with MRI will be even more difcult. In a recent publication by Silverstein et al (39), it was the Panels unanimous opinion that percutaneous needle biopsy represents best practice and should be the new gold standard for initial diagnosis. It should essentially replace open biopsy in this role. Breast ultrasound has become a valued imaging modality for breast abnormalities. Large core needle biopsies decrease the rate of upstaging when excisional biopsy is performed after core needle biopsy. New devices are being developed to biopsy lesions that keep the sample intact and avoid fragmentation of the specimen. These devices may improve our staging and margin assessment capabilities. If we are to improve screening and diagnosis, a radically different approach is needed. We now look for a structural change that can be palpated or seen with imaging. Awaiting recognizable tissue changes on imaging studies limits the ability to provide early detection. The rate of positive biopsies, whether core needle biopsy or open surgical biopsy has remained stable at about 2025%, thus illustrating the need for higher specicity and resolution in imaging and for novel approaches that identify neoplastic change at a molecular level. S.C.W.

REFERENCES
1. American Cancer Society. Breast Cancer Facts and Figures 20072008. Atlanta, GA: American Cancer Society; 2007. 2. American Cancer Society. MRIs emerging role in breast cancer screening. The American Cancer Society now recommends MRI in addition to mammography for women at high risk for breast cancer. Harv Womens Health Watch 2007;15(2):13. 3. Smith RA, Saslow D, Sawyer KA, et al. American Cancer Society guidelines for breast cancer screening: update 2003. CA Cancer J Clin 2003; 2007;53:141169. 4. Rim A, Chellman-Jeffers M. Trends in breast cancer screening and diagnosis. Cleve Clin J Med 2008;75(suppl 1):S2S9. 5. Hogben RK. Screening for breast cancer in England: a review. Curr Opin Obstet Gynecol 2008;20(6):545549. 6. Ringash J. Preventive health care, 2001 update: screening mammography among women aged 4049 years at average risk of breast cancer. Can Med Assoc J 2001;164(4):469476. 7. Nemec CF, Listinsky J, Rim A, et al. How should we screen for breast cancer? Mammography, ultrasonography, MRI. Cleve Clin J Med 2007;74(12):897904. 8. Galit W, Green MS, Lital KB, et al. Routine screening mammography in women older than 74 years: a review of the available data. Maturitas 2007;57(2):109119. 9. Tice JA, Feldman MD. Full-eld digital mammography compared with screen-lm mammography in the detection of breast cancer: rays of light through DMIST or more fog? Breast Cancer Res Treat 2008;107(2):157165. 10. Berman CG. Recent advances in breast-specic imaging. Cancer Control 2007;14(4):338349.

11. Yankaskas BC, Schell MJ, Bird RE, et al. Reassessment of breast cancers missed during routine screening mammography: a community-based study. AJR Am J Roentgenol 2001;177(3):535541. 12. Freer TW, Ulissey MJ. Screening mammography with computer-aided detection: prospective study of 12,860 patients in a community breast center. Radiology 2001;220(3):781786. 13. Brem RF, Rapelyea JA, Zisman G, et al. Evaluation of breast cancer with a computer-aided detection system by mammographic appearance and histopathology. Cancer 2005;104(5): 931935. 14. Irwig L, Houssami N, Van Vliet C, et al. New technologies in screening for breast cancer: a systematic review of their accuracy. Br J Cancer 2004;90(11):21182122. 15. Greene T, Cocilovo C, Estabrook A, et al. A single institution review of new breast malignancies identied solely by sonography. J Am Coll Surg 2006;203(6):894898. 16. Bassett LW, Kimme-Smith C, Sutherland LK, et al. Automated and hand-held breast US: effect on patient management. Radiology 1987;165(1):103108. 17. Elmore JG, Armstrong K, Lehman CD, et al. Screening for breast cancer. JAMA 2005; 293(10):12451256. 18. Kriege M, Brekelmans CT, Boetes C, et al. Efcacy of MRI and mammography for breastcancer screening in women with a familial or genetic predisposition. N Engl J Med 2004;351(5):427437. 19. Buadu LD, Murakami J, Murayama S, et al. Breast lesions: correlation of contrast medium enhancement patterns on MR images with histopathologic ndings and tumor angiogenesis. Radiology 1996;200(3):639649. 20. Nunes LW. Architectural-based interpretations of breast MR imaging. Magn Reson Imaging Clin N Am 2001;9(2):303320. 21. Liberman L, Morris EA, Dershaw DD, et al. MR imaging of the ipsilateral breast in women with percutaneously proven breast cancer. AJR Am J Roentgenol 2003;180(4):901910. 22. Port ER, Park A, Borgen PI, et al. Results of MRI screening for breast cancer in high-risk patients with LCIS and atypical hyperplasia. Ann Surg Oncol 2007;14(3):10511057. 23. Rosen EL, Eubank WB, Mankoff DA, et al. FDG PET, PET/CT, and breast cancer imaging. Radiographics 2007;27(suppl 1):S215S229. 24. Tafra L, Cheng Z, Uddo J, et al. Pilot clinical trial of 18 F-uorodeoxyglucose positronemission mammography in the surgical management of breast cancer. Am J Surg 2005;190(4):628632. 25. Berg WA, Gutierrez L, NessAiver MS, et al. Diagnostic accuracy of mammography, clinical examination, US, and MR imaging in preoperative assessment of breast cancer. Radiology 2004;233(3):830849. 26. Hruska CB, Boughey JC, Phillips SW, et al. Scientic Impact Recognition Award: Molecular breast imaging: a review of the Mayo Clinic experience. Am J Surg 2008;196(4):470476. 27. Knight DC, Lowell DM, Heimann A, et al. Aspiration of the breast and nipple discharge cytology. Surg Gynecol Obstet 1986;163(5):415420. 28. Zajdela A, Ghossein NA, Pilleron JP, et al. The value of aspiration cytology in the diagnosis of breast cancer: experience at the Fondation Curie. Cancer 1975;35(2):499506. 29. Painter RW, Clark WE II, Deckers PJ, et al. Negative ndings on ne-needle aspiration biopsy of solid breast masses: patient management. Am J Surg 1988;155(3):387390. 30. Smith C, Butler J, Cobb C, et al. Fine-needle aspiration cytology in the diagnosis of primary breast cancer. Surgery 1988;103(2):178183. 31. Vetrani A, Fulciniti F, Benedetto G, et al. Fine-needle aspiration biopsies of breast masses. An additional experience with 1153 cases (1985 to 1988) and a meta-analysis. Cancer 1992;69(3):736740. 32. Palombini L, Fulciniti F, Vetrani A, et al. Fine-needle aspiration biopsies of breast masses. A critical analysis of 1956 cases in 8 years (19761984). Cancer 1988;61(11):22732277. 33. Bell DA, Hajdu SI, Urban JA, et al. Role of aspiration cytology in the diagnosis and management of mammary lesions in ofce practice. Cancer 1983;51(7):11821189. 34. Kaufman M, Bider D, Weissberg D, et al. Diagnosis of breast lesions by ne needle aspiration biopsy. Am Surg 1983;49(10):558559. 35. Smallwood J, Herbert A, Guyer P, et al. Fine needle aspiration cytology and the diagnosis of breast disease. Br J Surg 1983;72:841843. 36. Patel JJ, Gartell PC, Smallwood JA, et al. Fine needle aspiration cytology of breast masses: an evaluation of its accuracy and reasons for diagnostic failure. Ann R Coll Surg Engl 1987;69(4):156159. 37. Parker SH, Burbank F, Jackman RJ, et al. Percutaneous large-core breast biopsy: a multiinstitutional study. Radiology 1994;193(2):359364. 38. Dahlstrom JE, Sutton S, Jain S, et al. Histological precision of stereotactic core biopsy in diagnosis of malignant and premalignant breast lesions. Histopathology 1996;28(6):537541. 39. Silverstein MJ, Recht A, Lagios MD, et al. Special report: Consensus conference III. Imagedetected breast cancer: state-of-the-art diagnosis and treatment. J Am Coll Surg 209(4): 504520, October, 2009.

CHAPTER

3
INTRODUCTION
Over the past few decades the use of breast imaging has increased, with more emphasis being placed on ultrasound (US) and magnetic resonance imaging (MRI) than ever before. While mammography remains the front line in screening and rst-time diagnosis, US and MRI allow a more accurate characterization of lesions and symptomatic ndings. The number of breast cancer detections has increased, as have the instances of surgical breast interventions. In order to detect the abnormal changes in the breast, breast surgeons and breast imagers must be familiar with the normal ndings of the postsurgical breast. The techniques of biopsy, implantation, and reconstruction have also evolved, changing the breast imaging ndings as well. This chapter reviews the mammographic, sonographic, and MRI imaging of the breast after reduction, benign biopsy, conservation treatment, augmentation, and reduction, as well as autologous and nonautologous reconstruction.

Erini Makariou Anousheh Sayah

Imaging of the Surgically Altered Breast


nostic assessment and should be available for the radiologists review. Comparisons can demonstrate stability of a benign lesion or interval change in an active or malignant lesion. In many cases, comparisons will lower the number of radiographic images needed for the ultimate diagnosis. Signs of malignancy on mammography include spiculated lesions, architectural distortions, pleomorphic, casting, or linear calcications, and/or asymmetry (Fig. 3.2).

ULTRASOUND: BASIC PRINCIPLES


Ultrasound is an essential component in the workup of a palpable or mammographically evident lesion. In breast US, sound waves are emitted into the breast, and an image is created by the returning sound waves received by the ultrasound detector. Advantages of breast ultrasound include the ability to better characterize the composition of breast parenchyma and to determine whether breast lesions are solid or cystic (Fig. 3.3). Ultrasound can be used for a targeted region of the breast. It is also highly specific, relatively inexpensive, and widely available. Sonography is ideal for guided drainage or biopsy of lesions. Poor visualization of microcalcifications, which are often a sign of malignancy, is the ultrasounds main disadvantage. In addition, ultrasound can be labor intensive. However, whole-breast sonography is breaking ground as the rst line of imaging (2,3).

MAMMOGRAM: BASIC PRINCIPLES


A review of the basics of mammography and mammographic interpretation is essential for understanding the imaging of the surgically altered breast. Mammography is performed on a dedicated, low-dose radiographic unit. The unit compresses the breast to allow separation of parenchymal structures, improve contrast and resolution, and minimize x-ray dose. Digital mammography units are quickly replacing lm-screen units. Digital mammography captures x-ray information after it passes through the breast in a digital formatwithout a lmthat can be viewed, edited, and transferred electronically to viewing stations and picture archiving and communications systems viewers. Standard mammographic views include craniocaudal (CC) and mediolateral (MLO) views (Fig. 3.1). In a craniocaudal view, the breast is compressed from top to bottom. In a MLO view, the breast is compressed obliquely side to side, parallel to the plane through the axilla and the pectoralis muscles. These complementary views allow three-dimensional localization of a lesion of interest. Radiopaque markers placed on the breast by the technologist indicate a skin lesion, palpable lesion, or visible scar. A screening study is performed on an asymptomatic patient after the age of 40 years according to American College of Radiology guidelines (1). A diagnostic examination is performed when there are suspicious signs or symptoms or if the screening study was abnormal. During the diagnostic examination, the radiologist may request other specialized views, such as spot compression or magnication views, to further evaluate a suspicious area or lesion. A concomitant ultrasound exam may be performed to better characterize a lesion as solid or cystic. In all cases, old comparison views are critical in the diag-

MAGNETIC RESONANCE IMAGING: BASIC PRINCIPLES


MRI of the breast has evolved into an important tool in breast imaging with increasing indications for its use. Contrastenhanced breast MRI indications include (a) evaluation of the extension of known breast cancer, (b) detection of contralateral breast cancer in women with newly diagnosed breast cancer, (c) screening for women who are at high risk and/or positive for BRCA1 and BRCA2, (d) assessment of neoadjuvant chemotherapy response, (e) evaluation of chest wall invasion or mastectomy site for recurrence, and (f) detection of breast cancer in women with axillary metastases and a normal mammogram (46). Morphologic characterization and dynamic enhancing pattern of a lesion play an important role in MRI interpretation. The high sensitivity of MRI but its not so high specicity create many false-positive results and callbacks for further evaluation, including second-look ultrasound studies and biopsies (Fig. 3.4). Despite this, MRI has very high negative predictive value for invasive ductal cancer in women with questionable ndings on mammogram and ultrasound studies (7,8). The newly recognized but rare side effect of MRI, nephrogenic sclerosing brosis, is related to intravenous administration

16

Chapter 3 Imaging of the Surgically Altered Breast

17

Figure 3.1. Screening mammogram. A: Craniocaudal view, right breast. B: Craniocaudal view, left breast. C: Mediolateral oblique view, right breast. D: Mediolateral oblique view, left breast.

18

Section I Oncology and Oncoplastic Surgery

Figure 3.2. A: Diagnostic mammogram, craniocaudal view, cancer. B: Diagnostic mammogram, mediolateral oblique view, cancer. C: Diagnostic mammogram, spot compression, cancer. D: Diagnostic ultrasound, cancer.
of MRI contrast agents. Special attention is needed for women with impaired renal function or renal failure (9). standard procedure. Preoperative imaging can change the case management approach in a signicant number of cases: 18% using US and 11% to 30% using MRI (1012). US and MRI are generally more sensitive than mammography for invasive carcinomas, especially in dense and heterogeneous breasts. MRI is commonly used for the detection of multicentric and multifocal diseases once cancer is diagnosed (Fig. 3.5). Most additional tumor foci (87%) are located in the same

PREOPERATIVE IMAGING
Preoperative imaging allowing better delineation of the extent of a tumor prior to denitive treatment is becoming a

Chapter 3 Imaging of the Surgically Altered Breast

19

Figure 3.3. A: Mediolateral oblique view, cancer and cyst. B: Spot compression, cancer and cyst. C: Ultrasound, cancer and cyst. D: Ultrasound, biopsy cancer and cyst.

quadrant as the original tumor (10). Axillary and internal mammary chain nodes can also be evaluated. Suspicious nodes lose the normal fatty hilum and may enhance more than other nodes (10).

BENIGN BIOPSY CHANGES


Breast biopsies may be performed in the radiology suite or in the operating room by a breast surgeon. Core biopsies are often performed with radiographic, sonographic, or MRI guidance under local anesthesia. An 8- to 14-gauge core needle either in a spring-loaded or vacuum-loaded device is used for sampling. In most cases, a localizing clip is placed in the biopsy site for future reference. A postcore biopsy mammogram is

performed to verify the relationship of the clip to the biopsy bed and to serve as a new baseline. Postcore biopsy mammographic changes are few and very uncommon. In cases of clip placement, a small metallic clip should be visible at the biopsy site. Clips may demonstrate some migration from the area of initial placement (13). In cases with postbiopsy parenchymal hemorrhage, a localized area of increased density corresponding to increased uid and blood may be seen. Needle tracts may be noted as subtle, cylindrical mammographic densities in a projection parallel to the biopsy tract with 11-gauge needles. Fourteengauge needles have not been shown to produce any detectable abnormality (14). Following vacuum-assisted core biopsy, gas pockets and hematomas are common, but they resolve within 2 to 4 weeks (15) (Fig. 3.6). Overall, postcore

20

Section I Oncology and Oncoplastic Surgery

C D

Figure 3.4. A: Axial magnetic resonance imaging, cancer. B: Sagittal magnetic resonance imaging, cancer. C: Ultrasound, second-look cancer. D: Ultrasound, biopsy cancer.
biopsy changes should not be recognized on mammography after approximately 6 months; any density after this period likely represents an abnormality and should be further evaluated (16). Postexcisional breast biopsies, which involve the removal of a larger amount of breast tissue, demonstrate signicantly more imaging ndings. Fifty percent of benign excisional breast biopsies show some mammographic change (17). Postsurgical mammograms are ideally performed at about 3 to 6 months after surgery and serve as new baseline views. Benign pathologies, however, may not prompt postsurgical imaging unless there is a need to conrm successful removal of a lesion or evaluate for postoperative complications. In a postsurgical mammogram, a thin metallic marker is placed on the surgical skin scar to indicate its location on the images. The most commonly viewed postexcisional change is architectural parenchymal distortion, followed by overlying focal skin thickening (17) (Fig. 3.7). These changes are seen mostly in the rst 6 months after surgery (18). Other ndings include calcications or fat necrosis. Occasionally, 6 or more months after the procedure (18), calcications form in the postexcisional bed. Most are dystrophic in nature or associated with fat necrosis or oil cysts. Small irregular calcications mimicking malignancy may also be seen and should be closely monitored for malignancy.

SPECIMEN IMAGING
Biopsy samples can be imaged radiographically or sonographically in order to verify the removal of the lesion or of calcications or to assess surgical margins. The specimen xray is more sensitive than the in vivo mammogram due to increased resolution from the lack of surrounding attenuating breast tissue, increased penetration due to sample compression, decreased scatter radiation, lack of motion, and ability to use higher radiation doses (19). In fact, specimen views may show calcications that were not seen before the biopsy (20) (Fig. 3.8). Only lesions seen sonographically before biopsy are imaged sonographically after excision. MRI is not technically possible for specimen imaging. However, MRI needle localization specimens are often mammographically evaluated to show the integrity of the wire.

Chapter 3 Imaging of the Surgically Altered Breast

21

C D

Figure 3.5. A: Craniocaudal view, left breast contralateral. B: Mediolateral oblique view, left breast contralateral. C: Ultrasound, left breast. D: Axial magnetic resonance imaging, contralateral cancer.

IMAGING THE POSTREDUCTION MAMMOPLASTY BREAST


Most changes after breast reduction are identied in the lower breast, with skin thickening and distorted architecture most commonly seen on mammography. The ducts may appear to converge lower than the nipple, since the nipple is often reimplanted superiorly. Due to the surgical trauma from reduction, common postsurgical ndings can be seen, including fat necrosis, oil cysts, and epidermal inclusion cysts. On US or MRI, skin thickening is easily detected. However, in the absence of a focal lesion, the breast parenchyma will likely show no difference from the normal breast (21,22) (Fig. 3.9).

IMAGING THE CONSERVATIVELY TREATED BREAST


Current widespread use of breast conservation therapy necessitates familiarity with postconservation imaging, most importantly to aid in detection of residual tumor or recurrence. Conservation treatment includes lumpectomy with or without axillary node dissection and/or radiation, tailored to each patients individual needs. Surveillance after conservation includes mammography, US, and/or MRI examination, in conjunction with physical examination. Mammography continues to be the rst line of imaging for screening of postlumpectomy patients, although sensitivity

22

Section I Oncology and Oncoplastic Surgery

Figure 3.6. Craniocaudal view, right breast post core biopsy.


is lower than in nontreated breasts due to confounding postoperative changes (23). Early postoperative mammography is performed to conrm the removal of the lesion, identify postoperative uid collections, detect residual and recurrent

cancers, and screen for metachronous cancers in either breast. Views are performed approximately 2 weeks after surgery, prior to radiation treatment, at a time when postsurgical pain and edema have lessened and hematomas have resolved. A wire marker is applied to the surgical scar to identify the surgical plane, and CC and MLO views are obtained. Compression spot magnication views of the lumpectomy site are performed to evaluate for residual calcications, especially if calcications were present in the original tumor. In order to establish a postoperative baseline, a unilateral examination is also performed 6 months after completion of conservative therapy. Annual bilateral mammograms are performed thereafter to monitor for disease presence. Serial 6monthly exams may be performed for several years postdiagnosis if clinically warranted. Changes are most marked in the rst year after surgery, peaking at 6 to 12 months (24). During the following 5 years, postsurgical ndings (with the exception of calcications) decrease in prominence (25). Findings are usually multiple and include architectural distortion (82%), increased regional density (79%), skin thickening (54%), and calcications (3%). Lipid cysts, hematomas, and seromas may also be present (25). Postlumpectomy parenchymal scarring is usually identied as architectural distortion and increased parenchymal density. Postlumpectomy scarring is of relatively low density, interspersed with radiolucent areas that represent entrapped fat, which can be helpful in distinguishing it from malignancy. Postoperative uid collections are also culprits of increased regional breast density, seen in 50% of patients at 4 weeks and

Figure 3.7. A: Craniocaudal view of right breast, postexcision. B: Mediolateral oblique view of right breast,
postexcision.

Chapter 3 Imaging of the Surgically Altered Breast

23

Figure 3.8. A: Needle localization. B: Specimen radiograph.

25% of patients at 6 months after surgery (26). These uid collections can appear as a mass, but they should gradually decrease in size, stabilize, or completely resolve. As opposed to benign excisions, dead space is purposely left behind in malignant excisions to allow uid to ll in for better cosmesis (Fig. 3.10). Benign calcications after conservative therapy include oil cysts, dystrophic calcications, and calcied suture material. Calcications due to fat necrosis typically develop at or near the lumpectomy site, usually 2 years after treatment (27). The rate of tumor recurrence after lumpectomy and radiation, usually found 2 or more years after treatment (2831), is 5% to 10% at 5 years and 10% to 16% at 10 years. Mammography has been shown to detect two thirds of these cases (32). From 33% to 50% of local recurrences are detected on mammography prior to examination and are less likely to be invasive than those found physically (33,34). Typically, the mammographic appearance of recurrent tumors is similar to that of the original lesion, especially if found in the same quadrant (32). Recurrences are suspected with any increase in density or mass after postsurgical changes have stabilized or regressed at approximately 1 year following surgery. A new central mass may be a likely sign of malignancy, especially if it is associated with spiculations, skin retraction, and/or lack of central radiolucencies of interspersed fat. Pleomorphic or granular microcalcications are highly suggestive of recurrent or residual malignancy, notably if the original tumor had calcications. Mammography is currently the only imaging modality that can readily detect these calcications (Fig. 3.11). The reliability of ultrasound in evaluating the postconservation breast is limited not only because of its inability to detect suspicious microcalcications, but also because of the sono-

graphic distortion created by postsurgical scarring, which can mask malignancy. Scars and cancer are both hypoechoic and ill dened, and therefore differentiation between them is difcult (Fig. 3.12). However, ultrasound can be very helpful in ruling out malignancy if an anechoic, smooth cystic structure is seen, likely representing a simple cyst. MRI has high specicity for differentiation between postoperative brosis and recurrent disease, overcoming the postsurgical distortion that can confound other modalities as well as physical exam (35,36). As a result, MRI is now commonplace in the follow-up of patients with a history of conservative breast surgery. In addition, the characterization of lesion morphology and enhancement kinetics on MRI can help distinguish normal postoperative change from radiation-induced change, including brosis and skin thickening. MRI can be performed on women with histologically positive margins to evaluate for residual disease, especially for patients with noncalcic cancers or dense breasts. The procedure should be performed 28 days or more after surgery, although patients with positive margins who need immediate follow-up surgery may benet from earlier studies (6,37). It is important to have the surgical history when interpreting any breast MRI, as areas of architectural distortion and enhancement from fat necrosis may be misread as recurrence if the history is not available. Benign postoperative MRI ndings include skin thickening, brosis, fat necrosis, and seroma. The usual acute postoperative pattern at the lumpectomy site is a seroma cavity with a thin rim of enhancement due to postsurgical inammation. One third of cases show heterogeneous, concentric ring enhancement that is thought to represent the visualization of the healing process (38). Postoperative sites may appear enhanced up

24

Section I Oncology and Oncoplastic Surgery

Figure 3.9. A: Craniocaudal view of right breast, reduction. B: Craniocaudal view of left breast, reduction. C: Mediolateral oblique view of right breast, reduction. D: Mediolateral oblique view of left breast, reduction. E: Ultrasound of left breast, reduction with fat necrosis.

Chapter 3 Imaging of the Surgically Altered Breast

25

Figure 3.10. A: Craniocaudal view of right breast, postlumpectomy. B: Mediolateral oblique view of right breast, postlumpectomy. C: Axial contrast magnetic resonance imaging, postlumpectomy with seroma. D: Axial subtracted magnetic resonance imaging, right breast with seroma.

26

Section I Oncology and Oncoplastic Surgery

Figure 3.11. A: Craniocaudal view, right lumpecC tomy recurrence with calcications. B: Mediolateral oblique view, right lumpectomy recurrence with calcications. C: Spot compression, right lumpectomy recurrence with calcications.

to 6 months after surgery without radiation and up to 18 to 24 months after radiation therapy due to postsurgical reaction, inammation, or fat necrosis (6). Signs of carcinoma include seroma wall thickening of more than 5 mm and irregular or clumped enhancement around the resection cavity (37). Malignancy also demonstrates early and rapid contrast enhancement kinetics, often with early washout. Benign postoperative change, however, such as brosis or fat necrosis, has more gradual contrast uptake (35). Chest wall and axillary recurrences can be identied with the MRI even when clinically or mammographically occult. The average size of a

metastatic internal mammary node is 6 mm, but it can be as small as 4 mm (39,40).

IMAGING THE POSTMASTECTOMY BREAST WITHOUT RECONSTRUCTION


Mammography is technically reliant on available breast parenchyma, and therefore mammographic evaluation of the nonreconstructed postmastectomy breast is not generally useful. In order to better evaluate the postmastectomy bed, ultrasound

Chapter 3 Imaging of the Surgically Altered Breast

27

Figure 3.12. A: Mediolateral oblique view of


left breast, postlumpectomy with recurrence. B: Craniocaudal view of left breast, postlumpectomy with recurrence. C: Ultrasound of left breast, postlumpectomy with recurrence.

and MRI are used instead. These modalities are not used regularly, however, since recurrent tumors in nonreconstructed breasts are often clinically evident. Ultrasound is helpful in that it is readily available, inexpensive, nonionizing, and multiplanar and can effectively evaluate small abnormalities that are close to the skin surface. Normal postmastectomy ndings on ultrasound include four anatomic layers: skin, subcutaneous fat, pectoral muscle, and ribs/intercostal muscle/costal cartilage. Benign uid collections in the mastectomy site are well detected with sonography. US is excellent for differentiating these uid-lled lesions from solid, possibly malignant ones. Benign postoperative brosis appears as an irregular hypoechoic area with posterior acoustic shadowing and can be very difcult to differentiate from cancer. However, the ability of a lesion to change shape under compression is less consistent with malignancy (41). Computed tomography (CT) is occasionally used to evaluate the mastectomy bed. After radical mastectomy, there is no

subcutaneous fat, and only a small amount of residual pectoralis major muscle may be seen at the sternal or costal attachment. In a modied radical mastectomy, the amount of residual pectoralis muscle is variable. Any increased density, notably in the nearby lymph node chains, should warrant further evaluation for malignancy (42).

IMAGING THE POSTMASTECTOMY BREAST WITH AUTOGENOUS RECONSTRUCTION


Attitudes toward imaging patients with autogenous breast reconstruction have evolved rapidly over recent years. Patients were not typically imaged because of the belief that recurrences did not occur in these reconstructions. We now understand that this is not the case, and recurrences do in fact occur in autogenous myocutaneous aps (AMFs), including transverse rectus abdominis

28

Section I Oncology and Oncoplastic Surgery

myocutaneous (TRAM), latissimus, and deep inferior epigastric perforator aps, albeit with very low frequency. Currently, centers survey AMFs differently, with a combination of physical examination and mammography, ultrasound, and/or MRI. Mammography is used in this setting in an attempt to detect nonpalpable recurrences, although the detection rate may be low. In most centers, the ap is treated as a native breast in that it is imaged during the annual exam starting with CC and MLO views. In cases of patients with prior ductal carcinoma in situ, mammographic surveillance for TRAM may be benecial due to the microcalcications associated with recurrence (43). Autogenous myocutaneous aps appear as overall fat attenuation on mammography imaging, without ductal or glandular structures. Associated surgical scars and posteriorly placed surgical clips are often seen (Fig. 3.13). Attenuated soft tissue of the vascular pedicle may be in the posterior midap region, whereas the muscular component is seen on the MLO view anterior to the pectoralis muscle. The occasional patchy density is seen and often evolves into fat necrosis on subsequent examinations (44,45). The mammographic appearance of AMFs is well dened by Loyer et al., describing six radiopaque lines that correspond to the specic types of postreconstruction surgical scars (44). Other benign ndings include fat necrosis, noncalcied or calcied oil cysts, calcications, lymph nodes, and epidermal inclusion cysts. Fat necrosis is seen in 10% to 26% of free or pedicled TRAM aps (46,47) and in 2% of latissimus aps (48). Benign epidermal inclusion cysts can present as enlarged masses in TRAM aps (49) (Fig. 3.14). Recurrences in AMFs may present as irregular or spiculated masses, pleomorphic calcications, or masses with calcications. Recurrence can cause nipple retraction and tethering of the underlying pectoralis muscle (50). The reliability of mammography is limited in detecting small recurrences or recurrences that are in the periphery of the ap (51). Ultrasound can reveal recurrences in AMFs that go undetected on mammography (44%) and are clinically occult (54%). It has been suggested that this fact alone supports the need for whole-breast US evaluation of breast reconstructions. Often, the sonographic characteristics of the recurrence match those of the primary tumor. However, some malignant lesions may mimic benign entities like fat necrosis (51) (Fig. 3.15). MRI imaging for AMFs is used to conrm a nding seen on another modality or to determine the extent of recurrent disease. On MRI, a TRAM ap appears as abdominal fat and an atrophied rectus abdominus muscle along the chest wall, all the way to the native chest wall subcutaneous fat. A thin curvilinear line reaching the skin represents the skin of the ap (52). Benign ndings in a TRAM mimic those of the native breast: skin thickening, uid collections, brosis, fat necrosis, oil cysts, and scarring. Fibrosis often distorts the adjacent breast parenchyma and can sometimes be masslike with spiculations. Contrast-enhanced MRI images often show little to no enhancement. Any enhancement of brosis usually increases on delayed images. It is important to note that the enhancement pattern of granulation tissue may mimic malignancy as far out as 12 months after surgery. Fat necrosis demonstrates fat signal with peripheral contrast enhancement (Fig. 3.15). A fat-uid level may be present (52). Tumor recurrence in an AMF is reliably detected on MRI based on contrast enhancement characteristics. Spiculated masses with rapid contrast uptake, especially in a rimlike pattern, should raise suspicion. Recurrence in nearby axillary or

internal mammary nodal chains, manifesting as increased size or number, can also be detected (52). Appearances of TRAM aps on CT are fairly uniform. The TRAM will take the shape of a normal breast, but it is internally homogeneously fat attenuation. Again, a soft tissue band representing the abdominal skin is often seen all the way to the supercial skin. Surgical clips are identied in the chest wall at the rectus attachment. The abdominal rectus muscle will be absent with muscle crossover at the fth to seventh costal cartilage level (53).

IMAGING THE POSTMASTECTOMY BREAST WITH NONAUTOGENOUS RECONSTRUCTION


Implants placed after mastectomy may generate an ideal cosmetic result; however, subsequent imaging becomes less than ideal. Physical examination is critical in these cases, as a lack of underlying breast parenchyma allows most recurrences to be felt just underneath the skin. Unfortunately, mammographic and even sonographic evaluation for recurrence is extremely limited. MRI is currently the gold standard for follow-up or evaluation of lesions in the nonautogenously reconstructed breast.

IMAGING THE IMPLANTAUGMENTED BREAST


On mammography, implants obscure a large portion (22% to 83%) of normal breast parenchyma on standard MLO and CC views (54). On implant-displaced or Eklund views, the implant is displaced posteriorly during the image acquisition. Eklund views do not image the posterior breast, so standard views must also be performed (Fig. 3.16). Implants placed beneath the pectoralis muscles (subpectoral) often afford an easier view of the breast parenchyma versus those placed just behind the glandular tissue (retroglandular). Silicone gel implants are highly radiopaque ellipsoid structures on mammography. Saline implants are less radiodense; portions of the breast parenchyma may be seen in an overpenetrated examination. Some silicone implants demonstrate a fuzzy margin representing the textured coating applied to prevent contracture. Pointing or wrinkling at the superior aspect of the implant may be visualized and even palpated and should not be mistaken for a mass. A radiopaque number projecting over the implant indicates the volume in milliliters of silicone within the prosthesis (55,56). Silicone and saline implants have similar sonographic appearance, with the implant itself being anechoic. A reective anterior interface is seen between the implant and breast parenchyma in retroglandular implants and between the implant and pectoral muscle in subpectoral implants. Sometimes wrinkles, internal valves, and positioning rings can also be seen. US is used to evaluate clinically or mammographically evident lesions, as well as dense breasts or breasts in which displaced views cannot be performed. Due to depth limitations, however, US does not visualize the posterior implant surface well (55). Double-lumen implants have an inner silicone compartment and outer saline compartment or vice versa. In cases of rupture, this architecture prevents massive deation and asymmetry of the breast. Mammography can distinguish between

Chapter 3 Imaging of the Surgically Altered Breast

29

Figure 3.13. A: Mediolateral oblique view, right transverse rectus abdominis myocutaneous (TRAM).
B: Mediolateral oblique view, left TRAM. C: Axial magnetic resonance imaging, right TRAM. D: Sagittal magnetic resonance imaging, right TRAM.

the two compartments, whereas US is very limited in this aspect. As a result, mammography is typically used to evaluate outer lumen failure (57). MRI is the gold standard for imaging the implant-augmented breast. The MRI imaging correlates for 14 various types of implants is shown by Middleton et al. (58). MRI is a very useful and often rst-line screening technology in the diagnosis of implant

complications. Complications include capsular contraction, gel bleed, implant rupture, infection, and migration/herniation. Capsular contracture involves constriction of the outer brous capsule around the implant envelope. It is a common complication and believed to be the result of hypertrophic scar or subclinical infection (59). Typically, the implant becomes more spherical and rm to palpation. Implant rounding, irregular

30

Section I Oncology and Oncoplastic Surgery

Figure 3.14. Ultrasound, transverse rectus abdominis myocutaneous,


inclusion cyst.

Figure 3.15. A: Mediolateral oblique view, right transverse rectus abdominis myocutaneous (TRAM) with
fat necrosis. B: Sagittal magnetic resonance imaging, right TRAM with fat necrosis. C: Axial contrast MRI, right TRAM with fat necrosis. D: Axial subtracted magnetic resonance imaging, right TRAM with fat necrosis.

Chapter 3 Imaging of the Surgically Altered Breast

31

Figure 3.16. A: Craniocaudal (CC) view, right breast with implant. B: CC view, left breast with implant. C: Mediolateral oblique (MLO) view, right breast with implant. D: MLO view, left breast with implant. (continued)
borders, infoldings, compression of adjacent parenchyma, and capsular thickening may be seen on mammography. There may be anterior tenting of retroglandular implants around the nipple. Dense calcications and/or ossication around the implant may also be seen (55,56). US in general is limited in evaluating implants, and in most instances clinical contracture has a normal appearance on MRI (59). However, potential signs of contracture on MRI include thickening of the hypointense margin, abrupt contour rounding, and increased anteroposterior diameter relative to transverse diameter (57). Gel bleed is often not seen mammographically, although it may appear indirectly as capsular contracture (56). MRI does

32

Section I Oncology and Oncoplastic Surgery

Figure 3.16. (Continued) E: CC view, right breast implant displaced. F: CC view, left breast implant displaced. G: MLO view, right breast implant displaced. H: MLO view, left breast implant displaced.

Chapter 3 Imaging of the Surgically Altered Breast

33

not detect minimal amounts of gel bleed, and severe gel bleed may be confused with intracapsular rupture (60). Infection of the breast implant is uncommon and often associated with rupture. Staphylococcus epidermidis is usually the offending agent. MRI can be used initially to suggest infection if certain ndings are present: uid adjacent to a thickened capsule, uid collections or abscesses, and/or contrast enhancement. Persistent uid on subsequent MRI examinations suggests ongoing infections, whereas in cases of sterile rupture, the initial uid is resorbed over time (59). Migration is also uncommon but sometimes seen in cases in which steroids are instilled to decrease capsule formation. All imaging modalities demonstrate extension of a portion of the implant toward or below the inframammary fold (59). Implant rupture may be intracapsular or extracapsular. In intracapsular rupture, the implant envelope ruptures, while the brous capsule remains intact. The implant may appear as thinned or attened. On all modalities, especially MRI, long serpentine strands may be seen within the implant representing the collapsed implant shell. This nding is known as the linguine sign (61). Hyperintense globules of silicone may be found outside the implant on MRI. There may be areas of lateral migration (59). In extracapsular rupture, there is an additional rupture of the brous outer capsule, often with pockets of external free silicone. This extracapsular silicone is specic (97%) but insensitive (5%) and is seen in 11% to 23% of studies of surgically explanted prostheses (62,63). Free silicone globules are dense and spherical and may be located anywhere in the breast. With cases of free silicone injection, silicone globules with calcic rims can be seen along the pectoralis muscle or regional nodes or toward the nipple (55,64). Tiny amounts of extruded free silicone or collapsed outer shells that are obscured by the implant itself may not be picked up by conventional mammography. MRI is the only modality shown to be both highly sensitive and highly specic for both intracapsular and extracapsular rupture (65). Free silicone globules are seen as foci of low signal on fat-suppressed T1 sequences and high signal on T2. In cases of saline implant rupture, saline solution is absorbed by the body, and only the remnant of the collapsed shell is left behind. With outer compartment rupture in a double-lumen implant, very little change is identied, and the implant resembles a single-lumen implant on MRI. Therefore, the diagnosis may be overlooked if the surgical history is not provided (59).

(66,67). As in most cases, comparison with previous mammography and detailed surgical history is extremely helpful. Postexplantation seromas occur early after surgery as the remaining brous capsule lls up with uid and can persist for many years. On mammography, they are well-circumscribed or irregular, uid-density structures. On US, seromas are at and either smooth and anechoic or irregular and hypoechoic (68).

EDITORIAL COMMENTS Dr. Makariou brings her expertise to the complex issue of mammographically evaluating the surgically altered breasts and gives practical and specic guidelines for recommendations and appropriate intervals for mammograms after breast surgery. The cumulative number of women with breast conserving surgery who undergo routine surveillance is increasing and cosmetic breast surgery has become more common, therefore both the surgeon and the mammographer must be familiar with the possible changes that can occur after surgery for both benign and malignant disease. In theory, patients with non-invasive disease should not die of their disease. Yet, of the 10% of women with DCIS treated with breast conserving surgery who develop an in breast recurrence, half of them will have invasive disease. Twenty to twenty-ve per cent of patients with invasive breast cancer will ultimately die of their disease. These patients are a challenging population, since the post-operative and post-radiation changes make detection more difcult and the stakes are incredibly high, especially for those patients who develop invasive cancer after an initial diagnosis of non-invasive cancer. It is important to remember that there are millions of women who have had breast augmentation, mastopexy and breast reduction. Information presented in this chapter should be part of the informed consent for any patient contemplating elective surgery to alter her breast size or contour. Most patients and perhaps many surgeons are unaware of the signicant reduction in the volume of breast tissue that is imaged in patients who have had augmentation, especially when the implants are in the subglandular position. In addition, capsular contracture further decreases the amount of tissue that can be visualized by mammography. Patients undergoing augmentation should be counseled about the additional mammographic views, and therefore additional radiation, necessary to visualize more of the breast tissue when implants are in place. Similarly, procedures for biopsy of mammographic abnormalities in the patient with an implant in place are fraught with the risk of injury to the implant during invasive procedures. Another controversial issue is imaging of the reconstructed breast after autologous tissue transfer. Detection by palpation in these patients is more difcult than in those with an implant reconstruction. Decisions about routine imaging must weigh the risk and probable location of recurrence against the cost of routine imaging and the possibility of false positives. Beware of MRI in the patient with a tissue expander. Skin burns can occur if a patient with a tissue expander has an MRI. It is important to make sure the patient, as well as other health care providers who might order an MRI before exchange to a permanent implant, are aware of this phenomenon.

IMAGING THE POSTEXPLANTATION BREAST


Due to the recent increase in the number of breast implant removal procedures, more and more associated postsurgical changes are seen on routine imaging. The reasons for breast implant explantation include recent adverse publicity, reported complications, reported association between free silicone and immune-related disorders, and the known decreased utility of mammography in implant imaging (66). Mammographic ndings are usually in the posterior midbreast. They include parenchymal distortion, redistribution of parenchyma to the lower breast, lipid-cyst formation from fat necrosis, skin thickening, and coarse, plaquelike calcications of the residual brous capsule. Residual silicone-lled lymph nodes, or silicone granulomas, are often present. Spiculations may form around these granulomas and may be mistaken for neoplasm

34

Section I Oncology and Oncoplastic Surgery


33. Dershaw DD. Mammography in patients with breast cancer treated by breast conservation (lumpectomy with or without radiation). AJR Am J Roentgenol 1995;164:309316. 34. Stomper PC, Recht A, Berenberg AL, et al. Mammographic detection of recurrent cancer in the irradiated breast. AJR Am J Roentgenol 1987;148:3943. 35. Muller RD, Barkhausen J, Sauerwein W, et al. Assessment of local recurrence after breastconserving therapy with MRI. J Comput Assist Tomogr 1998;22:408412. 36. Dao TH, Rahmouni A, Campana F, et al. Tumor recurrence versus brosis in the irradiated breast: differentiation with dynamic gadolinium-enhanced MR imaging. Radiology 1993;187:751755. 37. Frei KA, Kinkel K, Bonel HM, et al. MR imaging of the breast in patients with positive margins after lumpectomy: inuence of the time interval between lumpectomy and MR imaging. AJR Am J Roentgenol 2000;175:15771584. 38. Whipp EC, Halliwell M. Magnetic resonance imaging appearances in the postoperative breast: the clinical target volume-tumor and its relationship to the chest wall. Int J Radiat Oncol Biol Phys 2008;72:4957. 39. Ojeda-Fournier H, Choe KA, Mahoney MC. Recognizing and interpreting artifacts and pitfalls in MR imaging of the breast. Radiographics 2007;27(suppl 1): S147S164. 40. Kinoshita T, Odagiri K, Andoh K, et al. Evaluation of small internal mammary lymph node metastases in breast cancer by MRI. Radiat Med 1999;17:189193. 41. Kim SM, Park JM. Normal and abnormal US ndings at the mastectomy site. Radiographics 2004;24:357365. 42. Shea WJ, de Geer G, Webb WR. Chest wall after mastectomy. Part I. CT appearance of normal postoperative anatomy, postirradiation changes, and optimal scanning techniques. Radiology 1987;162:157161. 43. Helvie MA, Wilson TE, Roubidoux MA, et al. Mammographic appearance of recurrent breast carcinoma in six patients with TRAM flap breast reconstructions. Radiology 1998;209:711715. 44. Loyer EM, Kroll SS, David CL, et al. Mammographic and CT ndings after breast reconstruction with a rectus abdominis musculocutaneous ap. AJR Am J Roentgenol 1991;156: 11591162. 45. Leibman AJ, Styblo TM, Bostwick J. Mammography of the postreconstruction breast. Plast Reconstr Surg 1997;99:698704. 46. Banic A, Boeckx W, Greulich M, et al. Late results of breast reconstruction with free TRAM aps: a prospective multicentric study. Plast Reconstr Surg 1995;95:11951204;discussion 12051206. 47. Kroll SS, Gherardini G, Martin JE, et al. Fat necrosis in free and pedicled TRAM aps. Plast Reconstr Surg 1998;102:15021507. 48. Delay E, Gounot N, Bouillot A, et al. Autologous latissimus breast reconstruction: a 3-year clinical experience with 100 patients. Plast Reconstr Surg 1998;102:14611478. 49. Helvie MA, Bailey JE, Roubidoux MA, et al. Mammographic screening of TRAM ap breast reconstructions for detection of nonpalpable recurrent cancer. Radiology 2002;224: 211216. 50. Hogge JP, Zuurbier RA, de Paredes ES. Mammography of autologous myocutaneous aps. Radiographics 1999;19(spec no):S63S72. 51. Edeiken BS, Fornage BD, Bedi DG, et al. Recurrence in autogenous myocutaneous ap reconstruction after mastectomy for primary breast cancer: US diagnosis. Radiology 2003;227:542548. 52. Devon RK, Rosen MA, Mies C, et al. Breast reconstruction with a transverse rectus abdominis myocutaneous ap: spectrum of normal and abnormal MR imaging ndings. Radiographics 2004;24:12871299. 53. LePage MA, Kazerooni EA, Helvie MA, et al. Breast reconstruction with TRAM aps: normal and abnormal appearances at CT. Radiographics 1999;19:15931603. 54. Hayes H, Vandergrift J, Diner WC. Mammography and breast implants. Plast Reconstr Surg 1988;82:18. 55. Ganott MA, Harris KM, Ilkhanipour ZS, et al. Augmentation mammoplasty: normal and abnormal ndings with mammography and US. Radiographics 1992;12:281295. 56. Steinbach BG, Hardt NS, Abbitt PL, et al. Breast implants, common complications, and concurrent breast disease. Radiographics 1993;13:95118. 57. Berg WA, Caskey CI, Hamper UM, et al. Diagnosing breast implant rupture with MR imaging, US, and mammography. Radiographics 1993;13:13231336. 58. Middleton MS, McNamara MP. Breast implant classication with MR imaging correlation. Radiographics 2000;20(3):E1. 59. DeAngelis GA, de Lange EE, Miller LR, et al. MR imaging of breast implants. Radiographics 1994;14:783794. 60. Berg WA, Anderson ND, Zerhouni EA, et al. MR imaging of the breast in patients with silicone breast implants: normal postoperative variants and diagnostic pitfalls. AJR Am J Roentgenol 1994;163:575578. 61. Gorczyca DP, Sinha S, Ahn CY, et al. Silicone breast implants in vivo: MR imaging. Radiology 1992;185:407410. 62. Caskey CI, Berg WA, Anderson ND, et al. Breast implant rupture: diagnosis with US. Radiology 1994;190:819823. 63. Brown SL, Silverman BG, Berg WA. Rupture of silicone-gel breast implants: causes, sequelae, and diagnosis. Lancet 1997;350:15311537. 64. Caskey CI, Berg WA, Hamper UM, et al. Imaging spectrum of extracapsular silicone: correlation of US, MR imaging, mammographic, and histopathologic ndings. Radiographics 1999;19(spec no):S39S51; quiz S261S262. 65. Everson LI, Parantainen H, Detlie T, et al. Diagnosis of breast implant rupture: imaging findings and relative efficacies of imaging techniques. AJR Am J Roentgenol 1994;163: 5760. 66. Hayes MK, Gold RH, Bassett LW. Mammographic ndings after the removal of breast implants. AJR Am J Roentgenol 1993;160:487490. 67. Stewart NR, Monsees BS, Destouet JM, et al. Mammographic appearance following implant removal. Radiology 1992;185:8385. 68. Soo MS, Kornguth PJ, Georgiade GS, et al. Seromas in residual fibrous capsules after explantation: mammographic and sonographic appearances. Radiology 1995;194:863866.

Perhaps, other modalities, such as MRI will eventually become the preferred method of detecting an in breast recurrence, however mammography will not be supplanted by MRI as the current best method of detecting recurrence manifest as microcalcications. S.C.W.

REFERENCES
1. Feig SA, DOrsi CJ, Hendrick RE, et al. American College of Radiology guidelines for breast cancer screening. AJR Am J Roentgenol 1998;171:2933. 2. Berg WA. Rationale for a trial of screening breast ultrasound: American College of Radiology Imaging Network (ACRIN) 6666. AJR Am J Roentgenol 2003;180:12251228. 3. Crystal P, Strano SD, Shcharynski S, et al. Using sonography to screen women with mammographically dense breasts. AJR Am J Roentgenol 2003;181:177182. 4. Orel SG, Schnall MD. MR imaging of the breast for the detection, diagnosis, and staging of breast cancer. Radiology 2001;220:1330. 5. Lehman CD. Role of MRI in screening women at high risk for breast cancer. J Magn Reson Imaging 2006;24:964970. 6. Lee CH. Problem solving MR imaging of the breast. Radiol Clin N Am 2004;42:919934. 7. Kelcz F, Santyr G. Gadolinium-enhanced breast MRI. Crit Rev Diagn Imaging 1995;36:287338. 8. Rankin SC. MRI of the breast. Br J Radiol 2000;73:806818. 9. Deo A, Fogel M, Cowper SE. Nephrogenic systemic brosis: a population study examining the relationship of disease development to gadolinium exposure. Clin J Am Soc Nephrol 2007;2:264267. 10. Berg WA, Gutierrez L, NessAiver MS, et al. Diagnostic accuracy of mammography, clinical examination, US, and MR imaging in preoperative assessment of breast cancer. Radiology 2004;233:830849. 11. Harms SE, Flamig DP, Hesley KL, et al. MR imaging of the breast with rotating delivery of excitation off resonance: clinical experience with pathologic correlation. Radiology 1993;187:493501. 12. Orel SG, Schnall MD, Powell CM, et al. Staging of suspected breast cancer: effect of MR imaging and MR-guided biopsy. Radiology 1995;196:115122. 13. Kass R, Kumar G, Klimberg VS, et al. Clip migration in stereotactic biopsy. Am J Surg 2002;184:325331. 14. Lamm RL, Jackman RJ. Mammographic abnormalities caused by percutaneous stereotactic biopsy of histologically benign lesions evident on follow-up mammograms. AJR Am J Roentgenol 2000;174:753756. 15. Liberman L, Hann LE, Dershaw DD, et al. Mammographic ndings after stereotactic 14gauge vacuum biopsy. Radiology 1997;203:343347. 16. Kaye MD, Vicinanza-Adami CA, Sullivan ML. Mammographic ndings after stereotaxic biopsy of the breast performed with large-core needles. Radiology 1994;192:149151. 17. Brenner RJ, Pfaff JM. Mammographic changes after excisional breast biopsy for benign disease. AJR Am J Roentgenol 1996;167:10471052. 18. Sickles EA, Herzog KA. Mammography of the postsurgical breast. AJR Am J Roentgenol 1981;136:585588. 19. Gombos EC, Huszar M, Cernik H, et al. Two-view specimen radiography in assessing the surgical margins of breast carcinoma. J Womens Imaging 2004;6:1622. 20. Sadowsky NL, Semine A, Harris JR. Breast imaging. A critical aspect of breast conserving treatment. Cancer 1990;65:21132118. 21. Miller CL, Feig SA, Fox JW. Mammographic changes after reduction mammoplasty. AJR Am J Roentgenol 1987;149:3538. 22. Brown FE, Sargent SK, Cohen SR, et al. Mammographic changes following reduction mammaplasty. Plast Reconstr Surg 1987;80:691698. 23. Shin JH, Han BK, Choe YH, et al. Ultrasonographic detection of occult cancer in patients after surgical therapy for breast cancer. J Ultrasound Med 2005;24:643649. 24. Hassell PR, Olivotto IA, Mueller HA, et al. Early breast cancer: detection of recurrence after conservative surgery and radiation therapy. Radiology 1990;176:731735. 25. Brenner RJ, Pfaff JM. Mammographic features after conservation therapy for malignant breast disease: serial findings standardized by regression analysis. AJR Am J Roentgenol 1996;167:171178. 26. Mendelson EB. Evaluation of the postoperative breast. Radiol Clin N Am 1992;30:107138. 27. Dershaw DD. Breast imaging and the conservative treatment of breast cancer. Radiol Clin N Am 2002;40:501516. 28. Fowble BL, Solin LJ, Schultz DJ, et al. Ten year results of conservative surgery and irradiation for stage I and II breast cancer. Int J Radiat Oncol Biol Phys 1991;21:269277. 29. Recht A, Silen W, Schnitt SJ, et al. Time-course of local recurrence following conservative surgery and radiotherapy for early stage breast cancer. Int J Radiat Oncol Biol Phys 1988;15:255261. 30. Solin LJ, Kurtz J, Fourquet A, et al. Fifteen-year results of breast-conserving surgery and denitive breast irradiation for the treatment of ductal carcinoma in situ of the breast. J Clin Oncol 1996;14:754763. 31. Harris KM, Costa-Greco MA, Baratz AB, et al. The mammographic features of the postlumpectomy, postirradiation breast. Radiographics 1989;9:253268. 32. Philpotts LE, Lee CH, Haffty BG, et al. Mammographic ndings of recurrent breast cancer after lumpectomy and radiation therapy: comparison with the primary tumor. Radiology 1996;201:767771.

CHAPTER

4
Breast Cancer Diagnosis, Prognosis, and Treatment in Augmented Women
INTRODUCTION
Over the years concerns have been raised about the possible effects of silicone implants on the incidence, detection, treatment, and prognosis of breast cancer. Since breast augmentation is popular, these are legitimate questions. Recent statistics published by the American Society of Aesthetic Plastic Surgery (ASAPS) indicate breast augmentation is the most popular cosmetic surgical procedure in the United States; nearly 356,000 primary breast augmentations were performed in 2008 (1). Carcinoma of the breast is also common (2). The American Cancer Society estimates that women in the United States have nearly a 1 in 7 (13.4%) lifetime risk of developing breast cancer (3); 182,460 new cases of invasive breast cancer were diagnosed in American women in 2008 (4). Extrapolating from these statistics, eventually 50,000 augmented women will be diagnosed annually with breast cancer. It is important to understand the potential effects of implants on the incidence, detection, treatment, and prognosis of breast cancer.

Neal Handel

While it clearly has been established that augmented women are not at increased risk for developing breast cancer, due to the frequency of this disease, many augmented women eventually will be diagnosed with breast cancer. This has resulted in persistent and valid concerns about the possible effects of implants on cancer detection (17,18). Conceivably, implants could alter physical examination of the breast, reduce the sensitivity of various imaging modalities, or even interfere with adequate biopsy of suspicious lesions.

PHYSICAL EXAMINATION OF THE AUGMENTED BREAST


Breasts implants, whether submammary, submuscular, or in a dual-plane pocket, always reside deep to the parenchyma. For that reason, the presence of the prosthesis alone should not compromise palpation of a lesion. However, there are numerous ways implants may alter physical examination of the breast. Sometimes breast augmentation (particularly when combined with mastopexy) causes parenchymal scarring or areas of fat necrosis. This may result in thickened regions or even discrete lumps palpable on physical examination. If such ndings are clinically suspicious, further diagnostic testing is indicated. A signicant number of augmented patients develop capsular contracture. Ordinarily contracture does not interfere with palpation of breast tissue, but occasionally the capsule tears, allowing part of the implant to herniate into adjacent parenchyma; this may result in a palpable (or even visible) mass within the breast (Fig. 4.1). Typically, such a palpable bulge or knuckle of the implant is not confusing to plastic surgeons. However, primary care physicians, gynecologists, and nurse practitioners may not be familiar with these ndings; when such an abnormal mass is identied, it needs to be differentiated from a pathologic lesion. Calcication of the capsule sometimes occurs, and rigid calcium deposits may be palpated immediately adjacent to the implant. These benign calcications must be distinguished on both physical examination and mammography from malignant microcalcications (Figs. 4.2A and 4.2B). One of the recognized complications of silicone gel implants is leakage of ller material, from either gel bleed or frank rupture of the elastomeric shell. When silicone gel leaks from the implant, it may elicits an inammatory foreign-body reaction, leading to brosis and sometimes formation of siliconomas. These abnormalities may be palpable adjacent to the implant or in other areas of the breast or chest wall (Fig. 4.3), depending upon where the silicone migrates. Siliconomas typically present as rm, discrete lumps and must be differentiated from other pathologic masses. If a silicone implant ruptures

IMPLANTS AND CANCER RISK


There have long been questions about a possible association between implants and the risk of developing carcinoma of the breast or other benign or malignant breast tumors. The origin of these concerns was based on the observation that when solid foreign bodies made of various different substances were implanted in rodents, they frequently elicited the development of sarcomas (5,6). This phenomenon, known as the Oppenheimer effect, has never been observed in humans (79). Numerous epidemiologic studies have investigated the incidence of breast cancer in augmented patients compared to nonaugmented cohorts. These studies unequivocally demonstrate that breast implants are not associated with an increased risk of developing carcinomas or other types of benign or malignant breast tumors (1012). In fact, recently published studies (1316) have documented a lower-than-expected incidence of breast cancer in augmented patients (Table 4.1). The observation that augmented women appear to be at a somewhat lower risk of developing breast cancer has led to speculation about possible mechanisms whereby breast implants might inhibit tumorigenesis. Among the hypotheses that have been suggested are that implants cause a heightened immune response, leading to earlier detection and destruction of precancerous cells; that the compression effect of the implant on surrounding breast tissue results in an alteration of cell growth rate; and that the implant acts as insulation, lowering the ambient temperature of the breast, with subsequent reduction of local tissue metabolic rates (13).

35

36

Section I Oncology and Oncoplastic Surgery

TABLE 4.1
Study
Brinton et al. 2000 (49) Pukkala et al. 2002 (81) Brisson et al. 2006 (82) Deapen et al. 2007 (83) Lipworth et al. 2009 (84)

Incidence of Breast Cancer in Augmented Patients


Total F/U (pt. y)
96,675 18,014 366,608 42,314 103,565

Country
United States Finland Canada United States Denmark and Sweden

x F/U (y)
12.9 8.3 14.9 15.5 16.6

Risk Estimate (95% CI)


0.89 (0.81.1) 0.5 (0.21.0) 0.75 (0.700.81) 0.69 (0.500.93) 0.73 (0.580.90)

CI, condence interval; F/U, follow-up; pt, patient.

and there is spread of silicone into the breast parenchyma or adjacent structures (extracapsular rupture), it is readily apparent on mammograms (Fig. 4.4). When the silicone gel leaking from the implant remains intracapsular, it may be difcult or impossible to detect on physical examination (silent rupture). This is especially true with newer-generation, more highly cohesive gel-lled implants. Intracapsular rupture can sometimes be diagnosed on mammography (Fig. 4.5) and can reliably be imaged by magnetic resonance imaging. Saline implants are inated with a ll tube inserted via a selfsealing valve on the anterior or posterior surface of the implant. In some patients, particularly those with a thin layer of breast tissue, the valve may be palpable. Generally it will be felt in the central portion of the breast, beneath the nipple-areolar complex. Even in cases in which the valve is on the posterior surface, the device can ip over and the valve may be felt. Surgeons sometimes unwittingly perform biopsies only to discover that the palpable mass is a ller valve. When performing surgical or needle biopsy of a suspected abnormality, caution must be exercised to avoid damaging the implant. In the case of ne needle aspiration or core needle biopsy, the implant can usually be manipulated away from the area where the sharp tip is introduced. However, if the lesion is

Figure 4.1. Augmented patient with a herniated silicone gel breast


implant presenting as a palpable and visible breast mass.

Figure 4.2. A: Dense calcication of scar tissue capsule surrounding silicone gel implant. B: Digital mammogram showing diffuse egg shell calcications within the capsule surrounding the implant.

Chapter 4 Breast Cancer Diagnosis, Prognosis, and Treatment in Augmented Women

37

Figure 4.3. Multiple siliconomas in breast parenchyma and adjacent soft tissues in a patient with a ruptured silicone gel implant.

immediately adjacent to the implant, it may be preferable to perform open biopsy to avoid damaging the prosthesis (Fig. 4.6). Core needle biopsy can be problematic because multiple needle insertions may be required to obtain adequate tissue samples, increasing the risk of puncturing the prosthesis. Vacuum-assisted biopsy (Mammotome, MIBB) facilitates biopsy in women with implants (Fig. 4.7) (19,20). With this technique, stereotactic mammography or real-time ultrasonography is used to guide the needle tip adjacent to the suspicious area. The vacuum-assisted biopsy needle can be accurately positioned near the lesion to avoid damaging the implant. Unlike core

Figure 4.5. Digital mammogram of a patient with intracapsular


rupture of a silicone gel implant; the arrow indicates abnormal contour where silicone has escaped from the implant but remains conned within the capsule.

Figure 4.4. Mammogram of a patient with extracapsular rupture


of a silicone gel implant, showing extravasation of free silicone into the ducts and breast parenchyma.

Figure 4.6. Mammogram of augmented patient with a breast cancer


in close proximity to breast implant.

38

Section I Oncology and Oncoplastic Surgery

Figure 4.7. Diagram of vacuum-assisted


E
(Mammotome, MIBB) biopsy in an augmented patient. A: The biopsy needle tip is guided adjacent to the suspicious area. B: The vacuum draws the tissue into the biopsy needle aperture. C: A rotating cutter is advanced to harvest tissue. D: The specimen has been transected. E: The vacuum withdraws and transports the specimen. F: A marker can be placed at the biopsy site to facilitate later radiologic follow-up.

Chapter 4 Breast Cancer Diagnosis, Prognosis, and Treatment in Augmented Women

39

needle biopsy, the vacuum-assisted biopsy probe is inserted just once into the breast through a single small skin incision. Multiple tissue samples may be taken by rotating the needle aperture and using vacuum assistance. The precision and directional capabilities of vacuum-assisted biopsy make this the preferred technique for percutaneous biopsy in augmented women. When open biopsy is performed, steps can be taken to minimize the risk of damaging the implant. Dissection is best performed with a blunt-tipped electrocautery. If the surface of the implant is encountered, care should be taken to avoid damaging the shell with any pointed or sharp instrument. If the surgical biopsy also includes a portion of the capsule, it is unnecessary to repair the capsule; a new layer of scar tissue will regenerate over the implant surface.

RADIOLOGICAL IMAGING OF THE AUGMENTED BREAST


MAMMOGRAPHY Routine mammographic screening of asymptomatic women facilitates early diagnosis of breast cancer. Over the years concerns have been raised about the accuracy of mammography in augmented patients (21,22). There are several ways implants may affect mammograms. The surgery can cause parenchymal scarring, resulting in architectural distortions, densities, or calcications that appear on mammography. Implants (particularly when present over a prolonged period of time) compress breast tissue, increasing radiodensity, reducing contrast, and potentially interfering with identication of subtle lesions (23). The best-quality mammograms are obtained when the breast is maximally compressed so the x-ray beam penetrates the thinnest possible layer of tissue. With less compression, the volume of visualized tissue per unit area increases, causing more superimposition and potentially reducing mammographic sensitivity. Because implants are less compliant than breast tissue, they make it difcult to achieve the desired compression. During

mammography the average nonaugmented breast can be compressed to a thickness of 4.5 cm, while the average augmented breast can be compressed only to a thickness of 7 cm (24). The most important factor, affecting mammography in the augmented breast is the radiopaque shadow cast by the implant. Early reports estimated that only 25% of the breast is visualized after augmentation (25). Gumucio et al. (26) demonstrated that both saline and silicone implants can totally obscure early lesions such as microcalcications. Hayes et al. (27) reported that 22% to 83% (38% on average) of the breast tissue could be obscured by the implant. The extent to which an implant shadow interferes with mammography depends upon its size (28) and radiodensity (29). The density of the shadow is determined primarily by the physical and radiologic characteristics of the ller material. Both silicone and saline create a dense, radiopaque shadow that completely blocks visualization of adjacent breast tissue. Over the years several prostheses (e.g., Misti Gold implant, Trilucent implant) containing alternative ller materials have been introduced. However, none of these llers proved entirely satisfactory and at the present time only saline- and silicone gellled implants are commercially available. My colleagues and I investigated how breast implants affect the amount of tissue visualized on mammograms (22,29). Preoperative and postoperative mammography was performed in a consecutive series of breast augmentation patients, and the amount of tissue visualized on each lm was measured. Changes in area visualized were correlated with various parameters, including the degree of capsular contracture, implant position (submammary vs. submuscular), type of mammography (compression vs. displacement), preoperative breast size, implant size, and implant type. Our study revealed that in most patients there is a decrease in measurable breast tissue on postaugmentation lms. The most important factor is capsular contracture: Little or no contracture (Baker 1 or 2) resulted in a 30% reduction in the area visualized, while moderate or severe contracture (Baker 3 or 4) resulted in a 50% reduction (Fig. 4.8). In patients who

Figure 4.8. Effect of contracture on area visualized


postaugmentation. Little or no contracture (Baker 1 or 2) results in about 30% reduction in the area visualized, while moderate or severe contracture (Baker 3 or 4) results in about 50% reduction.

40

Section I Oncology and Oncoplastic Surgery

Figure 4.9. Effect of worsening contracture. Left: Compression mammography in a patient before augmentation mammaplasty. Middle: Postaugmentation mammogram, at which time the patient had a Baker 1 capsule. Right: A subsequent mammogram, by which time the patient had developed Baker 4 capsular contracture.

Pre-op

Post-op compression

Post-op displacement

had serial mammography in the face of worsening contracture, there was progressive reduction in the amount of tissue visualized (Fig. 4.9). Implant position (submammary vs. submuscular) also proved important; on average, patients with submammary implants had a 37% reduction in area visualized, while patients with submuscular implants had only a 17% reduction. In order to facilitate mammography in augmented women, Eklund et al. (30) developed the displacement or push-back technique (Figs. 4.10A and 4.10B), by which the implant is displaced posteriorly to allow a greater proportion of breast tissue to be captured on the mammogram. Using standard compression mammography, Eklund et al. determined that up to 97% of the breast tissue could be obscured by the implant, greatly increasing the likelihood of missing a signicant lesion. The displacement technique led to an improvement in 99% of cases. Part of this improvement is likely attributable to the fact that implant displacement results in a compression advantage of up to 5 cm, leading to improved image quality and greater sensitivity. Subsequent studies conrmed the results of Eklund et al. in obtaining better visualization of breast tissue using implant displacement (31,32). Our study (33) also conrmed that slightly more tissue is visualized with displacement (average reduction of 25%) than with standard compression mammography (average decrease of 30%); however, with either technique

Figure 4.11. Compression versus displacement mammography. Left: Mammogram of a patient before augmentation. Middle: Postaugmentation compression mammogram. Right: Postaugmentation displacement mammogram. Slightly more tissue is visualized with displacement than with compression, but with either technique there is a substantial reduction in area visualized compared to the preaugmentation study.

there is a substantial reduction in area visualized compared to preaugmentation mammograms (Fig. 4.11). While no one refutes that the shadow cast by an implant interferes with visualization of breast tissue, there has been debate about whether this translates into diminished mammographic sensitivity. It has been established that mammography in nonaugmented women is highly sensitive. In nonaugmented women with palpable tumors, the mammogram is positive in 90% and the false-negative rate is 10%. There are several published reports suggesting that the false-negative rate in augmented patients is considerably higher (32,34,35). We recently reviewed the mammograms of all patients with palpable tumors treated over a 23-year period (36). Mammograms among 1741 nonaugmented women failed to visualize the tumor in 153 (false-negative rate of 8.8%). The mammograms of 87 augmented patients failed to reveal the lesion in 36 cases (false-negative rate of 41.4%). This difference is highly signicant (p 0.0001) (Table 4.2) and suggests that implants dramatically reduce the sensitivity of mammography.

Figure 4.10. A: Diagram of compression mammogA B


raphy. B: Diagram of displacement (Eklund technique) mammography.

Chapter 4 Breast Cancer Diagnosis, Prognosis, and Treatment in Augmented Women

41

TABLE 4.2

Sensitivity of Mammography in Women with Palpable Cancers


Augmented Number
36 51 87

effects breast implants have on conventional mammography will also apply to digital mammography. MAGNETIC RESONANCE IMAGING Magnetic resonance imaging (MRI) has proven useful in diagnosing breast implant ruptures and leakage (38,39). MRI can also be used as an adjunct to lm screen mammography for detecting parenchymal abnormalities in augmented women. MRI is not impaired by the presence of radiopaque implants, can be used to examine breast tissue compressed by the implant, and reliably images adjacent structures, such as the muscles and chest wall. Furthermore, scarring can be differentiated from malignancy because malignant lesions demonstrate an early and strong enhancement of the contrast medium (4042). However, MRI requires administration of intravenous contrast, is much costlier than conventional mammography, and has limitations in sensitivity and specicity. The International Consensus Conference recently issued a report on state-of-the-art diagnosis and treatment of breast cancer. This panel concluded that MRI might be helpful in pretreatment evaluation of newly diagnosed breast cancer in augmented women and for patients in whom mammography is inconclusive, such as women with injected silicone (43). However, conventional mammography remains the best tool for screening and diagnosing breast cancer, and MRI is not recommended as a cancerscreening tool in augmented patients. There is increasing data to support MRI screening for younger patients at high risk of breast cancer (e.g., BRCA1 or BRCA2 mutation, strong family or

Nonaugmented Number
Negative Positive Total p 0.0001. 153 1588 1741

%
8.8 91.2 100.0

%
41.4 58.6 100.0

DIGITAL MAMMOGRAPHY Digital mammography is a technique by which an electronic image of the breast is captured and stored on a computer, allowing the recorded data to be magnied, enhanced, or otherwise manipulated to increase sensitivity. A recently published clinical trial comparing digital to lm mammography demonstrated no difference in the accuracy of detecting breast cancer (37). No studies have been published specically comparing digital and lm mammography in augmented women. Some radiologists have observed that in patients with saline implants, the tissue beneath the implant shadow appears to be better visualized with digital mammography; this is particularly true if a manual technique is used instead of automated settings (Figs. 4.12A and 4.12B). However, it is likely that the same adverse

Figure 4.12. A: Digital mammography of a patient with a saline-lled implant using automated settings;
the implant appears as a dense, radiopaque shadow, effectively blocking visualization of all breast tissue within its path. B: Repeat digital mammogram of the same patient using a manual technique; structures previously hidden by the implant can now be visualized.

42

Section I Oncology and Oncoplastic Surgery

personal history of breast cancer). However, these high-risk patients probably should be discouraged from undergoing elective breast augmentation because implants might interfere with the earliest possible detection of cancer and may diminish the usefulness of breast conservation therapy (44). ULTRASOUND Breast ultrasound can be useful for detecting implant rupture or leakage (45,46) and has the advantage of being less expensive than MRI (47). However, ultrasound is not as sensitive or specic for detecting parenchymal abnormalities as mammography or MRI (48). Currently, ultrasound is most useful for characterizing masses, detecting unsuspected invasive disease in lesions presenting as microcalcifications, and measuring tumor size of mass lesions. There currently is no recognized role for ultrasound as a screening tool in augmented women.

TABLE 4.3

Palpability at Time of Diagnosis


Augmented Number
32 97 129

Nonaugmenteda Number
Nonpalpable Palpable Total 1756 2096 3852

%
45.6 54.4 100

%
24.8 75.2 100

p 0.0001. a Data on palpability unavailable for 70 nonaugmented patients.

EFFECTS OF IMPLANTS ON DISEASE STAGE AND PROGNOSIS


While there is a good deal of evidence that breast implants decrease the sensitivity of mammography, there are conicting reports regarding the stage of disease at the time of diagnosis in augmented women. Several years ago we reported that among our breast cancer population, augmented women were diagnosed at a comparatively advanced stage (18,23). Others have reported similar observations. In a multicenter study, Brinton et al. (49) found that augmented cancer patients had a lower incidence of in situ and local disease and a higher rate of axillary nodal metastases and distant spread than nonaugmented patients. Similarly, Karanas and et al. (50) reported a low rate of early lesions (stages 0 and 1) and a relatively high rate of advanced disease (stages 3 and 4) in augmented cancer patients. On the other hand, some published reports suggest that the stage of disease at diagnosis is equivalent in augmented and nonaugmented women (5154). Carlson et al. (55) demonstrated in their 1993 study that the pathologic staging found in augmented and nonaugmented cancer patients was similar. Deapen et al. (56) came to the same conclusion. Leibman and Kruse (31,32) found that 28% of breast cancers detected in augmented patients were asymptomatic at the time of diagnosis, implying that even in augmented patients, breast cancer can be detected while still in its occult stages. To further examine this question, we recently reviewed our experience with 4,082 consecutive breast cancer patients treated between 1981 and 2004 at the Breast Center in Van Nuys, California, and the Kenneth Norris Comprehensive Cancer Center in Los Angeles, California (36). For the purpose of comparing augmented and nonaugmented patients, only women with inltrating ductal, inltrating lobular, ductal carcinoma in situ (DCIS), and lobular carcinoma in situ were included (unusual tumors such as angiosarcomas and lymphomas were excluded). This yielded a total of 3,922 nonaugmented patients and 129 augmented patients in the nal analysis. All patients were entered into a prospective database, which included, among other information, tumor palpability, size of the primary (measured at the time of surgical excision), nuclear grade, the presence or absence of lymphovascular invasion, and axillary lymph node status. Breast cancer recurrence and mortality rates were carefully tracked. Mammograms were

reviewed (when available) to compare the sensitivity of mammography in augmented and nonaugmented patients with palpable lesions. The ndings in the two groups were compared. Statistical signicance was determined using appropriate methodology: Comparison of average tumor size was done with t-tests on independent groups; comparison of survival until recurrence and survival until death was done using log rank tests from Kaplan-Meier survival analysis; analyses of counts and percentages were done with chi-square tests. Among nonaugmented women, mean age at time of diagnosis was 53.5 years (range 22 to 95 years); in augmented patients, mean age was 46.8 years (range 29 to 71 years). In the augmented group, for cases in which data were available (N 104), implants were present a mean of 10.5 years (range 0.5 to 37 years). In cases in which information regarding the degree of capsular contracture was available (N 106) 30% were Baker grade 1, 40% were grade 2, 22% were grade 3, and 8% were grade 4. Augmented patients presented with a signicantly lower percentage of occult (nonpalpable) tumors (25% compared to 46%) (p 0.0001) (Table 4.3), a slightly lower incidence of early in situ lesions (27% compared to 33%), and a greater incidence of positive axillary lymph nodes (46% compared to 35%). Overall, however, there was no signicant difference in stage of disease between augmented and nonaugmented patients (Table 4.4). For purposes of comparing tumor size we considered only patients with inltrating ductal lesions (inltrating ductal tumors are the type most commonly encountered and measurement of which is most reliable). Among the 3,922 nonaugmented patients, there were 2,235 inltrating ductal cancers, with an average tumor size of 23.8 mm. Among 120 augmented patients, 86

TABLE 4.4

Stage of Disease at Time of Diagnosis


Augmentedb Number
35 37 48 8 128

Nonaugmenteda Stage
0 1 2 3 Total

Number
1272 1206 1092 225 3795

%
33.3 31.7 28.7 5.9 100

%
27.3 28.9 37.5 6.3 100

p 0.2496 (nonsignicant). a Data unavailable for 116 nonaugmented patients. b Data unavailable for 1 augmented patient.

Chapter 4 Breast Cancer Diagnosis, Prognosis, and Treatment in Augmented Women

43

TABLE 4.5

Mean Tumor Sizea


Number of Patients Mean Tumor Size
23.8 23.2 23.7 Alive Dead

TABLE 4.7

Breast Cancer Mortality Rate


Augmented Number
116 13

Nonaugmented Number
3510 412

Nonaugmented Augmented Total


a

2235 86 2321

%
89.5 10.5

%
89.9 10.1

p 0.8066 (nonsignicant). Patients with inltrating ductal cancer only.

p 0.6523 (nonsignicant).

had inltrating ductal lesions, with an average size of 23.2 mm (no signicant difference) (Table 4.5). Breast cancer recurrence rates (Table 4.6) and breast cancerspecic survival rates (Table 4.7) were the same for augmented and nonaugmented cancer patients. Kaplan-Meier analyses conrm that there was no significant difference in breast cancer recurrence (Fig. 4.13) or survival (Fig. 4.14) between the two groups over time. Our data revealed that augmented cancer patients were less likely to present with occult lesions and had a signicantly higher rate of false-negative mammograms; however, tumor size was virtually identical in augmented and nonaugmented women. One possible explanation is that implants may facilitate palpation of tumors. Others have suggested that the augmented breast is easier to examine (9); there are several reasons why this is plausible. Palpation of a breast lesion is dependent upon feeling the abnormality and distinguishing it from surrounding normal breast tissue. This is more difcult in women with large breasts and deep tumors because the lesion simply is not as accessible to the touch. Breast implants compress breast parenchyma and, over time, cause tissue atrophy. It is not uncommon to observe that the parenchymal envelope in augmented patients (particularly when implants have been present for many years) has been reduced to a thin layer, often just 1 to 2 cm in thickness. In our population implants had been present an average of more than 10 years prior to diagnosis, ample time for the prosthesis to cause tissue compression, thinning, and atrophy. This may explain why lesions of virtually the same size were more frequently palpable in augmented patients (Fig. 4.15).

TREATMENT OF BREAST CANCER IN AUGMENTED PATIENTS


The two currently accepted modalities for treatment of breast cancer are mastectomy and breast conservation therapy (BCT). There is little reason to believe that implants interfere with mastectomy. The prosthesis and scar tissue capsule are removed with the mastectomy specimen, and reconstruction may be per-

TABLE 4.6

Cancer Recurrence Rate


Nonaugmented Augmented Number
110 19

Number
No evidence of disease Recurrent disease 3158 764

%
80.5 19.5

%
85.3 14.7

p 0.4932 (nonsignicant).

formed as either an immediate or delayed procedure. In fact, the presence of a breast implant may actually facilitate healing because the mastectomy aps have been delayed as a result of undermining performed at the time of augmentation. BCT consists of lumpectomy, axillary lymph node dissection, whole-breast irradiation, and, in selected cases, a boost to the tumor bed (57). BCT has proven effective in the majority of women with breast cancer and yields survival rates equivalent to mastectomy for women with stage 1 (T1 N0), stage 2A (T0 N1, T1 N1, T2 N0), and stage 2B (T2 N1, T3 N0) breast cancer (5864). The cosmetic results of BCT have been reported as good to excellent in the majority of cases (6568). Because of the excellent survival rates and good cosmetic results, BCT is now often considered the treatment of choice in patients with stage 1 or stage 2 disease (69,70). Several studies have investigated radiation physics in the presence of implants (7173). Neither silicone gellled nor saline-lled implants attenuate x-rays, and it is widely held by physicists and radiation oncologists that x-ray therapy can be effectively delivered in the presence of an implant; BCT is believed to be equally curative in augmented and nonaugmented patients (74,75). It is further established that electron beams, due to their nite penetration and rapid falloff, cause minimal damage to adjacent normal structures (such as the lungs and heart). Studies of radiation dose distribution reveal no signicant difference in the amount of radiation delivered to adjacent structures in the presence of implants (73). The other major concerns regarding the use of BCT in augmented women are cosmetic results and radiation-related complications. Some investigators report that good results are routinely obtained following irradiation of the augmented breast (7678). Others suggest a high rate of capsular contracture and poor cosmesis (79). Several years ago we reviewed our experience with a consecutive series of augmented breast cancer patients who underwent BCT (80). Between 1981 and 1994 we treated 66 augmented women with primary breast cancer; 27 had modied radical mastectomy, three (with DCIS) had lumpectomy only, and three had other forms of treatment. The remaining 33 patients underwent BCT. Of the patients who received BCT, 4 were explanted prior to radiation, and in 3 others complete details regarding treatment were unavailable. The remaining 26 patients comprised the study population. These patients ranged in age at time of augmentation from 22 to 55 years (mean age 37 years) and ranged in age at time of cancer diagnosis from 31 to 67 years (mean age 45 years). The interval from augmentation to cancer diagnosis was 0.5 to 20 years (mean 7.5 years). The rmness of each breast (according to the Baker classication) was rated at the time of cancer diagnosis and at intervals following completion of radiation therapy. Data were also collected regarding the rates and reasons for secondary implant surgery after BCT.

44

Section I Oncology and Oncoplastic Surgery

Figure 4.13. Breast cancer recurrence.


Kaplan-Meier plot of cumulative cancer recurrence in augmented and nonaugmented patients (no signicant difference).

Figure 4.14. Breast cancer mortality. KaplanMeier plot of breast cancerspecic survival in augmented and nonaugmented patients (no signicant difference).

Figure 4.15. Palpation of a lesion may be facilitated by


the long-term presence of an implant, which causes atrophy, thinning, and compression of breast parenchyma.

Chapter 4 Breast Cancer Diagnosis, Prognosis, and Treatment in Augmented Women

45

TABLE 4.8

Change in Baker Grade Following Breast Conservation Therapy (BCT)


Before Treatment After BCT
3.08 1.73

CONCLUSIONS
Due to the prevalence of breast cancer in the population it is inevitable that many augmented women will develop carcinoma of the breast. There remain concerns about the effect of implants on breast cancer detection, prognosis, and treatment. Multiple studies document that implants obscure mammograms, and there are data to suggest that the sensitivity of mammography is reduced in augmented women. Because of the possible adverse effects of implants on visualization of breast tissue, screening mammography may not be ideal in augmented patients, and it may be preferable to perform diagnostic mammography. When evaluating these patients, physical and mammographic ndings should be correlated. Any palpable abnormalities should be studied with ultrasound. In appropriate cases, magnetic resonance imaging should be considered as an adjunct. Careful review of a large series of breast cancer patients treated over a 23-year period revealed that augmented women presented signicantly more often with palpable tumors and had a much higher rate of false-negative mammography. Despite this, tumor size, stage of disease, recurrence rates, and breast cancerspecic survival were virtually identical in augmented and nonaugmented patients. These ndings suggest that tumors of equal size may be more easily palpated in augmented patients, and this benecial effect may compensate for the impairment of mammography. When it comes to the treatment of breast cancer in augmented patients, there is little reason to believe that implants interfere with mastectomy or breast reconstruction. On the other hand, there is ample evidence that breast conservation therapy may be compromised in augmented women. These patients experience a high rate of radiation-induced contracture, frequently require reoperation, and are prone to postoperative complications because of the adverse effect of radiation on wound healing. In addition to compromised cosmesis and a high rate of

Cancer side Opposite side

1.19 1.15

Twenty-eight augmented cancer patients.

Average Baker grade at time of diagnosis was 1.19 on the cancer side and 1.15 on the opposite side. At the latest follow-up visit after radiation therapy, average Baker grade was 3.08 on the treated side and 1.73 on the opposite side (see Fig. 4.14). Altogether, 17 (65%) of the augmented women treated with BCT had a signicant increase in contracture on the treated side (signicant increase was dened as a change from either Baker grade 1 or 2 to Baker grade 3 or 4). Among the 17 women with radiation-induced contracture, average Baker grade on the treated side went from 1.06 at the time of diagnosis to 3.71 following completion of radiation. There was also an increase in rmness on the opposite side, which rose from an average Baker grade of 1.06 to 1.94 (Table 4.8). The interval from completion of radiation to onset of capsular contracture averaged 22.4 weeks. Figure 4.16 shows an example of radiation-induced capsular contracture in an augmented patient treated with BCT. Eight patients with radiation-induced contracture required revision surgery. Five had explantation, capsulectomy, and replacement with new implants, and two had unilateral explantation and autologous (transverse rectus abdominis myocutaneous ap) reconstruction. One patient had bilateral explantation and capsulectomy without replacement. Based on this experience, it appears the majority of augmented patients treated with BCT will have unsatisfactory cosmetic results, and many will require secondary corrective procedures.

Figure 4.16. Left: Augmented patient diagnosed with cancer of the right breast (location of the tumor is
indicated by the circular mark adjacent to the nipple-areolar complex). Right: Following breast cancer therapy, the patient developed radiation-induced capsular contracture (Baker 4).

46

Section I Oncology and Oncoplastic Surgery

reoperation, there are other potential concerns for augmented women considering BCT. Because an implant (particularly in the presence of capsular contracture) may impair mammographic follow-up, the earliest possible detection of a local recurrence could be delayed. In addition, these patients are at increased risk of developing a second primary cancer in the opposite breast, and, hypothetically, the contralateral implant might interfere with early detection of a new cancer. Based on these considerations, BCT may be an undesirable option in augmented cancer patients, unless the implants are removed prior to treatment.

REFERENCES
1. Reece EM, Ghavami A, Hoxworth RE, et al. Primary breast augmentation today: a survey of current breast augmentation practice patterns. Aesthetic Surg J. 2009;29(2):116121. 2. The American Cancer Society. Breast Cancer Facts & Figures 20032004. Atlanta, GA: The American Cancer Society; 2003. 3. Leis HP. Epidemiology in breast cancer. In: Strombeck JO, Rosato FE, eds. Surgery of the BreastDiagnosis and Treatment of Breast Diseases. Stuttgart, Germany: Georg Thieme Verlag; 1986. 4. The American Cancer Society. Cancer Facts & Figures 2008. Atlanta, GA: The American Cancer Society; 2009. 5. Turner FC. Sarcomas at sites of subcutaneously implanted Bakelite disks in rats. J Natl Cancer Inst. 1941;2:8186. 6. Oppenheimer BS, Oppenheimer ET, Stout AP. Sarcomas induced in rats by implanting cellophane. Proc Soc Exp Biol Med. 1948;67:3338. 7. Hoopes JE, Edgerton MT, Shelley W. Organic synthetics for augmentation mammoplasty: their relation to breast cancer. Plast Reconstr Surg. 1967;39(3):263270. 8. Brand KG, Johnson KH, Buon LC. Foreign body tumorigenesis. CRC Crit Rev Toxicol. 1976;4(4):353394. 9. Morgan RW, Elcock M. Artificial implants and soft tissue sarcomas. J Clin Epidemiol. 1995;48(4):545549. 10. Deapen DM, Pike MC, Casagrande JT, et al. The relationship between breast cancer and augmentation mammaplasty: an epidemiologic study. Plast Reconstr Surg. 1986;77(3): 361368. 11. Brinton LA, Malone KE, Coates RJ, et al. Breast enlargement and reduction: results from a breast cancer casecontrol study. Plast Reconstr Surg. 1996;97(2):269275. 12. McLaughlin JK, Nyren O, Blot WJ, et al. Cancer risk among women with cosmetic breast implants: a population-based cohort study in Sweden. J Natl Cancer Inst. 1998;90(2): 156158. 13. Deapen DM, Bernstein L, Brody GS. Are breast implants anticarcinogenic? A 14-year follow-up of the Los Angeles study. Plast Reconstr Surg. 1997;99(5):13461353. 14. Hoshaw SJ, Klein PJ, Clark BD, et al. Breast implants and cancer: causation, delayed detection, and survival. Plast Reconstr Surg. 2001;107(6):13931407. 15. Dreyfuss DA, Singh S, Dowlatshahi K. Silicone implants as an anticarcinogen. Surg Forum. 1987;38:587592. 16. Su CW, Dreyfuss DA, Krizek A. Silicone implants and the inhibition of cancer. Plast Reconstr Surg. 1995;96(3):513518. 17. Jakub JW, Ebert MD, Cantor A, et al. Breast cancer in patients with prior augmentation: presentation, stage, and lymphatic mapping. Plast Reconstr Surg. 2004;114(7):17371742. 18. Silverstein MJ, Handel N, Gamagami P. The effect of silicone gellled implants on mammography. Cancer. 1991;68(5 suppl):11591163. 19. Trevathan-Ramirez D. Innovations in breast disease diagnosis. Radiol Technol. 1998;70(2): 197203. 20. Cangiarella J, Waisman J, Symmans WF, et al. Mammotome core biopsy for mammary microcalcication: analysis of 160 biopsies from 142 women with surgical and radiologic follow-up. Cancer. 2001;91(1):173177. 21. Rintala AE, Svinhufvud UM. Effect of augmentation mammaplasty on mammography and thermography. Plast Reconstr Surg. 1974;54(4):390396. 22. Handel N, Silverstein MJ, Gamagami P, et al. Factors affecting mammographic visualization of the breast after augmentation mammaplasty. JAMA. 1992;268(14):19131917. 23. Silverstein MJ, Handel N, Gamagami P, et al. Breast cancer in women after augmentation mammoplasty. Arch Surg. 1988;123(6):681685. 24. Monsees BS, Destouet JM. Mammography in aesthetic and reconstructive breast surgery. Perspect Plast Surg. 1991;5:103107. 25. Wolfe JN. On mammography in the presence of breast implants [Letter]. Plast Reconstr Surg. 1978;62(2):286288. 26. Gumucio CA, Pin P, Young VL, et al. The effect of breast implants on the radiographic detection of microcalcification and soft-tissue masses. Plast Reconstr Surg. 1989;84(5): 772778. 27. Hayes H Jr, Vandergrift J, Diner WC. Mammography and breast implants. Plast Reconstr Surg. 1988;82(1):18. 28. Beisang AA, Geise RA, Ersek RA. Radiolucent prosthetic gel. Plast Reconstr Surg. 1991;87(5):885892. 29. Handel N, Silverstein MJ, Gamagami P. The effect of silicone implants on mammography and breast cancer detection. Perspect Plast Surg. 1993;7:114. 30. Eklund GW, Busby RC, Miller SH, et al. Improved imaging of the augmented breast. Am J Roentgenol. 1988;151(3):469473. 31. Leibman AJ, Kruse BD. Breast cancer: mammographic and sonographic ndings after augmentation mammoplasty. Radiology. 1990;174(1):195198. 32. Leibman AJ, Kruse BD. Imaging of breast cancer after augmentation mammoplasty. Ann Plast Surg. 1993;30(2):111115. 33. Silverstein MJ, Handel N, Gamagami P, et al. Mammographic measurements before and after augmentation mammaplasty. Plast Reconstr Surg. 1990;86(6):11261130. 34. Silverstein MJ, Handel N, Gamagami P, et al. Breast cancer diagnosis and prognosis in women following augmentation with silicone gellled prostheses. Eur J Cancer. 1992;28(23): 635640. 35. Fajardo LL, Harvey JA, McAleese KA, et al. Breast cancer diagnosis in women with subglandular silicone gel lled augmentation implants. Radiology. 1995;194(3):859862. 36. Handel N, Silverstein MJ, Breast cancer diagnosis and prognosis in augmented women Plast Reconstr Surg. 2006;118(3):587593. 37. Pisano ED, Gatsonis C, Hendrick E, et al. Diagnostic performance of digital versus lm mammography for breast cancer screeningthe results of the American College of Radiology Imaging Network (ACRIN) Digital Mammographic Imaging Screening Trial (DMIST). N Engl J Med. 2005;353(17):17731783.

ACKNOWLEDGMENTS
The author wishes to acknowledge the contributions of his colleagues who were instrumental in the design and execution of several of the studies referenced in this manuscript. These include Melvin J. Silverstein, Parvis Gamagami, Bernard Lewinsky, James Waisman, and J. Arthur Jensen.

EDITORIAL COMMENTS I am commonly asked for my opinion about breast augmentation by patients contemplating the procedure. I think it is important for patients to understand that after augmentation, twice as many mammographic images are required with Eklund views, and yet there is still less breast tissue imaged than on preaugmentation mammography. Nonetheless, the author has made a compelling case that even though implants reduce the sensitivity of mammography, the stage at diagnosis in augmented patients is equivalent to that of nonaugmented patients. The data presented emphasize the importance of physical exam in augmented patients for breast cancer detection. There is no reason to suspect that implants cause cancer or that they worsen the prognosis. It is clear, however, that the presence of implants makes diagnostic and therapeutic interventions more difcult. For this reason, I try to discourage augmentation in the high-risk individual, not only because of the imaging limitations, but also because biopsy options become more limited, and there is concern that the implant may be injured. In addition, adjuvant radiotherapy after breast-conserving surgery for cancer with an implant in place may result in capsular contracture and thus interfere with subsequent imaging and detection of a recurrence or new primary. The plastic surgeon should be sure to obtain a preaugmentation mammogram based on age-appropriate recommendations and pursue workup of any abnormality detected before proceeding with the augmentation. Cancer that develops in an augmented breast does not always have the typical appearance of a malignancy. Tumor growth patterns may be altered by the thinning of the breast tissue that occurs from the constant pressure exerted by the implant. When performing surgery for cancer in an augmented breast, the oncologic surgeon should be aware of the potential of the alterations imposed on the native breast tissue by the implant and alter surgical technique accordingly. S.C.W.

Chapter 4 Breast Cancer Diagnosis, Prognosis, and Treatment in Augmented Women


38. Ahn CY, Shaw WW, Narayanan K, et al. Denitive diagnosis of breast implant rupture using magnetic resonance imaging. Plast Reconstr Surg. 1993;92(4):681691. 39. Holmich LR, Fryzek JP, Kjoller K, et al. The diagnosis of silicone breast-implant rupture: clinical ndings compared with ndings at magnetic resonance imaging. Ann Plast Surg. 2005;54(6):583589. 40. Everson LI, Parantainen H, Detlie T, et al. Diagnosis of breast implant rupture: imaging findings and relative efficacies of imaging techniques. AJR Am J Roentgenol. 1994; 163(1):5760. 41. Westerhof JP, Fischer U, Moritz JD, et al. MR imaging of mammographically detected clustered microcalcications: is there any value? Radiology. 1998;207(3):675681. 42. Hickman PF, Moore NR, Shepstone BJ. The indeterminate breast mass: assessment using contrast enhanced magnetic resonance imaging. Br J Radiol. 1994;67(793):1420. 43. Silverstein MJ, Lagios MD, Recht A, et al. Image-detected breast cancer: state of the art diagnosis and treatment. J Am Coll Surg. 2005;201(4):586597. 44. Handel N, Lewinsky B, Silverstein M, et al. Conservation therapy for breast cancer following augmentation mammaplasty. Plast Reconstr Surg. 1991;87(5):873878. 45. Azavedo E, Bone B. Imaging breasts with silicone implants. Eur Radiol. 1999;9(2):349355. 46. Shestak KC, Ganott MA, Harris KM, et al. Breast masses in the augmentation mammaplasty patient: the role of ultrasound. Plast Reconstr Surg. 1993;92(2):209216. 47. Peters W, Pugash R. Ultrasound analysis of 150 patients with silicone gel breast implants. Ann Plast Surg. 1993;31(1):79. 48. Piccoli CW. Imaging of the patient with silicone gel breast implants. Magn Reson Imaging Clin N Am. 2001;9(2):393408, viiviii. 49. Brinton LA, Lubin JH, Burich MC, et al. Breast cancer following augmentation mammaplasty. Cancer Causes Control. 2000;11(9):819827. 50. Karanas YL, Leong DS, Da Lio A, et al. Surgical treatment of breast cancer in previously augmented patients. Plast Reconstr Surg. 2003;111(3):10781083. 51. Clark CP III, Peters GN, OBrien KM. Cancer in the augmented breast: diagnosis and prognosis. Cancer. 1993;72(7):21702174. 52. Friis S, McLaughlin JK, Mellemkjaer L, et al. Breast implants and cancer risk in Denmark. Int J Cancer. 1997;71(6):956958. 53. Birdsell DC, Jenkins H, Berkel H. Breast cancer diagnosis and survival in women with and without breast implants. Plast Reconstr Surg. 1993;92(5):795800. 54. Cahan AC, Ashikari R, Pressman P, et al. Breast cancer after breast augmentation with silicone implants. Ann Surg Oncol. 1995;2(2):121125. 55. Carlson GW, Curley SA, Martin JE, et al. The detection of breast cancer after augmentation mammaplasty. Plast Reconstr Surg. 1993;91(5):837840. 56. Deapen D, Hamilton A, Bernstein L, et al. Breast cancer stage at diagnosis and survival among patients with prior breast implants. Plast Reconstr Surg. 2000;105(2):535540. 57. Recht A, Harris JR. Selection of patients with early-stage breast cancer for conservative surgery and radiation. Oncology. 1990;4(2):2330. 58. Veronesi U, Saccozzi R, DelVecchio M, et al. Comparing radical mastectomy with quadrentectomy, axillary dissection, and radiotherapy in patients with small cancers of the breast. N Engl J Med. 1981;305(1):611. 59. Harris JR, Hellman S. Primary radiation therapy for early breast cancer. Cancer. 1983;51(12 suppl):25472552. 60. Montague ED, Ames FC, Schell SR, et al. Conservative surgery and irradiation as an alternative to mastectomy in the treatment of clinically favorable breast cancer. Cancer. 1984;54(11 suppl):26682672. 61. Fisher B, Bauer M, Margolese R, et al. Five-year results of a randomized clinical trial comparing total mastectomy and segmental mastectomy with or without radiation in the treatment of breast cancer. N Engl J Med. 1985;312(11):665673.

47

62. Calle R, Vilcoq JR, Zafrani B, et al. Local control and survival of breast cancer treated by limited surgery followed by irradiation. Int J Radiat Oncol Biol Phys. 1986;12(6):873878. 63. Fisher B, Redmond C, Poisson R, et al. Eight-year results of a randomized clinical trial comparing total mastectomy and lumpectomy with or without radiation in the treatment of breast cancer. N Engl J Med. 1989;320(13):822828. 64. Rose MA, Olivotto I, Cady B, et al. The long-term results of conservative surgery and radiation therapy for early breast cancer. JAMA. 1991;265:391398. 65. Harris JR, Levene MB, Svensson G, et al. Analysis of cosmetic results following primary radiation therapy for stage I and stage II carcinoma of the breast. Int J Radiat Oncol Biol Phys. 1979;5(2):257261. 66. Clarke D, Martinez A, Cox RS. Analysis of cosmetic results and complications in patients with stage I and state II breast cancer treated by biopsy and irradiation. Int J Radiat Oncol Biol Phys. 1983;9(12):18071813. 67. Rose MA, Olivotto I, Cady B, et al. Conservative surgery and radiation therapy for early breast cancer: long term cosmetic results. Arch Surg. 1989;124(2):153157. 68. Berrino P, Campora E, Leone S, et al. Correction of type II breast deformities following conservative cancer surgery. Plast Reconstr Surg. 1992;90(5):846853. 69. NIH Consensus Conference. Treatment of early stage breast cancer. JAMA. 1991;265(3): 391395. 70. Schain WS, Fetting JH. Modied radical mastectomy versus breast conservation: psychosocial considerations. Semin Oncol. 1992;19(3):239243. 71. Ryu J, Yahalom J, Shank B, et al. Radiation therapy after breast augmentation or reconstruction in early or recurrent breast cancer. Cancer. 1990;66(5):844847. 72. McGinley PH, Powell WR, Bostwick J. Dosimetry of a silicone breast prosthesis. Radiology. 1980;135(1):223224. 73. Krishnan L, Krishnan EC. Electron beam irradiation after reconstruction with silicone gel implant in breast cancer. Am J Clin Oncol. 1986;9(3):223226. 74. Kuske RK, Schuster R, Klein E, et al. Radiotherapy and breast reconstruction: clinical results and dosimetry. Int J Radiat Oncol Biol Phys. 1991;21(2):339346. 75. Shedbalkar AR, Devata A, Padanilam T. A study of effects of radiation on silicone prosthesis. Plast Reconstr Surg. 1980;65(6):805810. 76. Stabile RJ, Santoro E, Dispaltro F, et al. Reconstructive breast surgery following mastectomy and adjunctive radiation therapy. Cancer. 1980;45(11):27382743. 77. Der Hagopian RP, Zaworski RE, Sugarbaker EV, et al. Management of locally recurrent breast cancer adjacent to prosthetic implants. Am J Surg. 1981;141(5):590592. 78. Jacobson GM, Sause WT, Thompson JW, et al. Breast irradiation following silicone gel implants. Int J Radiat Oncol Biol Phys. 1986;12(5):835838. 79. Halpern J, McNeese MD, Kroll SS, et al. Irradiation of prosthetically augmented breasts: a retrospective study on toxicity and cosmetic results. Int J Radiat Oncol Biol Phys. 1990; 18(1):189191. 80. Handel N, Lewinsky B, Jensen JA, et al. Breast conservation therapy after augmentation mammaplasty: is it appropriate? Plast Reconstr Surg. 1996;98(7):12161224. 81. Pukkala E, Boice JD Jr, Hovi SL, et al. Incidence of breast and other cancers among Finnish women with cosmetic breast implants, 19701999. J Long Term Eff Med Implants. 2002; 12(4):271279. 82. Brisson J, Holowaty EJ, Villeneuve PJ, et al. Cancer incidence in a cohort of Ontario and Quebec women having bilateral breast augmentation. Int J Cancer. 2006;118(11):2854 2862. 83. Deapen DM, Hirsch EM, Brody GS. Cancer risk among Los Angeles women with cosmetic breast implants. Plast Reconstr Surg. 2007;119(7):19871992. 84. Lipworth L, Tarone RE, Friis S, et al. Cancer among Scandinavian women with cosmetic breast implants: a pooled long-term follow-up study. Int J Cancer. 2009;124(2):490493.

CHAPTER

5
Pathology of Breast Disorders
Pathology of the breast encompasses a wide variety of disorders, including benign, premalignant, and malignant diseases, as well as disorders of uncertain malignant potential. A variety of infections and systemic diseases may affect the breast. This chapter presents a review of the pathology of breast diseases with an emphasis on common diseases, biomarkers, and emerging concepts that impact clinical practice. The functional unit of the breast is the terminal ductal lobular unit. This is composed of small acini, which drain into a terminal duct. The terminal duct is the rst tributary of the ductal system of the breast, which functions to extrude milk from the nipple. The entire lobular and ductal structure of the breast is lined by two layers of cells, the inner epithelial layer and the outer myoepithelial layer. Breast cancer typically refers to breast carcinoma, which arises by preferential growth of the inner epithelial layer. A useful corollary of this paradigm is that the demonstration of the absence of myoepithelial cells by immunohistochemistry can be used by the pathologist to determine the malignant potential of a lesion.

Baljit Singh

tecture, with or without brovascular cores. Architectural or cellular atypia in apocrine cells does not increase the risk of cancer development. Mild hyperplasia of the usual type falls into this category and is dened as epithelial proliferation in a duct that is less than four cells thick and does not cross the lumen. PROLIFERATIVE LESIONS WITHOUT ATYPIA Women with these lesions have a slight risk of development of breast carcinoma, 1.5 to 2 times that of the general population. This category includes moderate or orid hyperplasia of the usual type, sclerosing adenosis, small-duct papillomas, and broadenomas (1,7). Sclerosing adenosis is the most common lesion and refers to expanded lobular units with a proliferation of both acini and intervening stroma. Microcalcications are often seen in association with sclerosing adenosis and frequently correspond to benign calcications seen on mammography (Fig. 5.2). Rarely, a clinically palpable mass may be formed by a large number of lobules with cellular sclerosing adenosis and has been referred to as adenosis tumor. Usual ductal hyperplasia, moderate or orid, includes epithelial proliferation in ducts that are more than four cells thick and distend the ducts. Characteristically, they have a slitlike fenestrated pattern (Fig. 5.3). Solid and papillary patterns may also be seen. The cells may overlap, show slight variability in shape and size, and have a swirling or streaming pattern. Small duct papillomas arise in the peripheral duct system and tend to multiple. Microscopically, they are composed of brovascular papillae covered with the two cell types of the ductal system, the inner epithelial and the outer myoepithelial cells. ATYPICAL HYPERPLASIAS Atypical hyperplasias confer a risk of development of breast carcinoma that is 3.5 to 5 times that of the reference population. This category includes both atypical ductal hyperplasia and atypical lobular hyperplasia (1,2). These lesions are difcult diagnostic problems, with variable interobserver agreement (810). Their morphologic features are midway between those of usual hyperplasia and carcinoma in situ. Page et al. dened criteria for atypical ductal hyperplasia (ADH) that are widely used and include nuclear monomorphism, regular cell placement, and round (not fenestrated) spaces in part of the duct (Fig. 5.4). Atypical lobular hyperplasia (ALH) (11) refers to proliferation of lobular cells with distention of acini in no more than half of a lobule and may include pagetoid spread into adjacent ducts (12). Earlier studies showed that atypical hyperplasias do not have a linear progression to carcinoma and increase the risk of development of breast carcinoma in both breasts (2,13). They have, therefore, been considered to be general risk factors.

BENIGN DISORDERS
Fibrocystic change is the pathologic condition that correlates with lumpy, bumpy breasts. This term is applied to a plethora of benign changes in the breast, which are best categorized based on the subsequent risk of development of breast carcinoma. Dupont and Page (1,2) reviewed benign breast biopsies from 3,000 women and used well-dened criteria to categorize them into three groups: nonproliferative lesions, proliferative lesions without atypia, and atypical hyperplasia. This clinically relevant classication has been independently corroborated and sanctioned by a consensus conference of the College of American Pathologists (3,4). NONPROLIFERATIVE LESIONS This is the most common category of breast disorders and includes cysts, papillary apocrine change, mild hyperplasia of the usual type, and epithelial related calcications. Women with these lesions do not incur a higher risk of development of breast carcinoma than that of women who had no breast biopsy (relative risk, 0.89). In the early 20th century Joseph Bloodgood described blue cysts in the breast (blue domed cysts of Bloodgood) (5). Haagensen noted that cysts may form a palpable mass, and thus he termed them gross cysts (6). However, most cysts are small and can be visualized only on microscopic examination (Fig. 5.1). Not uncommonly, cystic change is accompanied by apocrine change of the lining epithelial cells. Oncocytic change is ubiquitous throughout the body, and these cells have characteristic abundant, pink, granular cytoplasm. Apocrine cells in the ductal system are often columnar and proliferate with a papillary archi-

48

Chapter 5 Pathology of Breast Disorders

49

Figure 5.1. Fibrocystic change, nonproliferative type. Two cysts are


lled with inspissated secretions. Dense brosis is seen in the background with normal and atrophic lobules.

Figure 5.3. Usual ductal hyperplasia. The ducts are full of overlapping cells with indistinct borders, forming a sievelike pattern.

A recent retrospective analysis found that the breast diagnosed with ALH is three times more likely to develop invasive carcinoma than the contralateral breast (14). These data suggest that ALH may lie somewhere between linear progression and generalized risk. Columnar cell hyperplasia (CCH) with or without atypia is a newly recognized morphologic entity. CCH without atypia is one of many hyperplastic lesions that slightly increase the relative risk of development of breast carcinoma and are grouped under brocystic change, proliferative type (15). CCH are frequently associated with microcalcications and may have mild, moderate, or marked atypia. Severe atypia typically has a micropapillary architecture and may be indistinguishable from ductal carcinoma in situ. CCH has been noted to be associated with ALH, lobular carcinoma in situ, and tubular carcinoma (16). As with other atypical proliferative lesions, there is a high level of interobserver variability among

pathologists in diagnosing CCH with atypia (17). Flat epithelial atypia is also a newly recognized morphologic entity (16). There is no prospective or retrospective evidence from clinical trials regarding the prognostic value of either CCH or at epithelial atypia. A diagnosis of an atypical lesion of any type as rendered on a core biopsy is an indication for a surgical biopsy. Atypical lesions are diagnosed in 4.3% to 6.7% patients who undergo a core biopsy for a mammographically detected lesion, and the subsequent surgical biopsy reveals intraductal carcinoma in 12.5% to 36% and invasive carcinoma in 0% to 14% of patients (1821). Magnetic resonance imaging (MRI) screening has been recommended for women at high risk for development of breast carcinoma. MRI-guided biopsies are increasingly utilized for premenopausal women with dense breasts (22). There is paucity of good radiologic/pathologic correlative studies for indenite lesions seen on MRI.

Figure 5.4. Atypical ductal hyperplasia. The duct has two populaFigure 5.2. Sclerosing adenosis. An enlarged lobule has numerous
acini in a sclerotic, dense stroma with focal microcalcications. tions of cells. Monomorphic cells with distinct borders are arranged around sharply demarcated round spaces. Overlapping cells are arranged around irregular spaces.

50

Section I Oncology and Oncoplastic Surgery

Figure 5.5. Radial scar. The central zone is sclerotic with a few
compressed ducts. Dilated ducts are seen at the periphery, some of which show usual ductal hyperplasia.

Figure 5.6. Fibroadenoma. The tumor is circumscribed and covered by a pseudo-capsule. It is composed of numerous ducts in a background of cellular stroma.

Atypical lesions of the breast are a diagnostic challenge for the surgical pathologist, and there is considerable interobserver variation among pathologists in interpreting these lesions. The Susan G. Komen for the Cure Foundation published a white paper on breast pathology (23) that recommends that the accuracy of diagnosis of breast lesions can be enhanced by specialty training, second opinions, and integration of pathologists into clinical care teams. RADIAL SCARS AND COMPLEX SCLEROSING LESIONS Radial scars are typically small areas of scarring (1 cm) surrounded by glandular elements. Their stellate morphology mimics a classic scirrhous carcinoma for both the mammographer and the pathologist. Typically, they are seen only on microscopy, which reveals an area of intense sclerosis in the center, surrounded by dilated ducts, sclerosing adenosis, and apocrine metaplasia (Fig. 5.5). Glands caught up in the central scirrhous zone may mimic invasive carcinoma on high magnication. The overall architecture of the lesion is critical in avoiding this pitfall, especially on frozen section. Numerous sclerotic lesions do not have the classic morphology of a radial scar but show varying degrees of sclerosis and ductal hyperplasia. These lesions are commonly referred to as complex sclerosing lesions. In a carefully performed casecontrol study, it was shown that women with biopsy-proven radial scars are at an increased risk for breast cancer. Women with proliferative lesions with atypia associated with radial scar had a relative risk of breast cancer of 3.0 (24).

BENIGN NEOPLASMS
FIBROADENOMA Fibroadenomas typically present as painless, mobile, rubbery masses. They are usually solitary but are occasionally multiple (25). They are most often present in the upper outer quadrant and are slightly more common in the left breast. Fibroadenomas are more common in Black women.

On gross examination, broadenomas are well-circumscribed masses that bulge on cut section. The cut surface may be gelatinous, and slitlike spaces can be discerned on occasion. On microscopic examination, broadenomas are biphasic and have epithelial and stromal components (Fig. 5.6). The epithelial component is usually formed by ducts lined by inner ductal and outer myoepithelial cells. The stroma consists of brous tissue with variable cellularity. Occasionally, the epithelial component is insignicant and the stromal component is hypocellular and densely sclerotic. This variant, hyalinized broadenoma, is invariably associated with coarse microcalcications, which may be worrisome to the mammographer. Juvenile broadenoma is a variant seen in young girls, and these tumors show both epithelial and stromal hypercellularity (26). They may be multiple, grow rapidly, and cause venous dilation in the overlying skin. Tubular adenoma is a subtype that has an abundance of small tubules on microscopic examination and is also common in young women (27). Complex broadenomas contain cysts larger than 3 mm, sclerosing adenosis, epithelial calcications, or papillary apocrine change. One study showed a higher risk of breast cancer (28) in patients with such lesions. Lactational adenomas are seen during pregnancy and in the postpartum period and may represent lactational changes superimposed on an underlying tubular adenoma or broadenoma. They present as a well-circumscribed mass, which on microscopy shows glands and ducts with secretory changes. Infarction, pain, and tenderness may complicate broadenomas during pregnancy. There is an increased relative risk (between 1.2 and 3.0) of invasive carcinoma in women with broadenoma (28). For this reason, broadenoma has been included in the category of proliferative lesions without atypia by some authors (29). SOLITARY (LARGE-DUCT) INTRADUCTAL PAPILLOMA These tumors typically arise in a large duct in the subareolar region and present with unilateral hemorrhagic discharge. One nested casecontrol study showed that papillomas with areas of ADH within them have a risk of breast carcinoma at

Chapter 5 Pathology of Breast Disorders

51

Figure 5.7. Intraductal papilloma. A large duct contains a


papillary structure with thick brovascular cores lined by ductal and myoepithelial cells.

Figure 5.8. Phyllodes tumor, benign. The tumor has a frondlike


architecture, with compressed ducts lined by ductal and myoepithelial cells (intracanalicular pattern).

that site, which is similar to the risk associated with ADH in the adjacent breast (30). On careful dissection papillomas appear as pearly, small, white nodules. Microscopically, they distend a duct and are composed of a stalk with branching thick brovascular cores lined by myoepithelial and ductal cells (Fig. 5.7). The proliferation of both cell types is an indicator of benignity. Complex growth patterns can make the distinction between a papilloma and papillary carcinoma challenging for the pathologist. The entire lesion should be submitted for microscopic examination to rule out any area of invasion. Papillomas typically do not show signicant pleomorphism, mitotic activity, and necrosis (31,32). PHYLLODES TUMOR This entity encompasses tumors that run the gamut from benign to malignant but mostly fall into the category of tumors of uncertain malignant potential (borderline). Conventionally, phyllodes tumors have been referred to as cystosarcoma phyllodes, an unfortunate term connoting malignant behavior. On gross examination, phyllodes tumors can be of any size and appear eshy, with sharp delineation from surrounding breast tissue. Microscopically, they have characteristic hypercellular stroma around the ductal elements, which are typically compressed (intracanalicular pattern) (Fig. 5.8). A high mitotic count, nuclear pleomorphism, and stromal overgrowth are the main criteria used to assess biological behavior (33,34). As with all stromal tumors, ample sampling is necessary because the sarcomatous component may be small and limited to a small portion of the tumor. Phyllodes tumors tend to have local recurrences and should be widely excised (35,36). Most tumors that metastasize show overt sarcomatous areas. NIPPLE ADENOMA Adenomas of the nipple present as ill-dened masses in the nipple region. Microscopically, they are composed of glandlike spaces associated with proliferation of ductal epithelium. The latter may show a pseudo-invasion pattern and extension into the nipple, which may clinically mimic Pagets disease. The

presence of both myoepithelial and epithelial layers in this lesion is an indicator of benignity. These lesions should be examined in their entirety because they have been reported in rare cases to be associated with carcinoma (37,38).

MISCELLANEOUS LESIONS
Microglandular adenosis is an uncommon lesion that mimics tubular carcinoma. It is usually seen in women older than 40 years and may present as an ill-dened mass. Microscopically, it is composed of small glands interspersed in the stroma and fat. The glands are lined by a single layer of epithelial cells but are surrounded by a basement membrane. Numerous authors have shown a tenuous concurrence of this lesion with carcinoma (3942). Lipoma is an ill-dened entity in the breast. Clinically apparent masses sometimes yield only fat without any glandular elements on excision and are diagnosed as lipoma. Fibromatosis is a locally invasive neoplastic condition that aficts numerous sites in the body and is best recognized as desmoid tumor of the abdominal wall. Microscopically, it consists of proliferation of benign-appearing spindle-shaped cells, which invade breast parenchyma. Wide excision is curative (4346). Rosen described the entity mucocele-like lesion, which consists of extravasated mucin from mucinous cysts and may present as a mass (47). Pseudoangiomatous hyperplasia of the mammary stroma may clinically present as a mass. The proliferating broblasts line slitlike spaces and mimic vascular proliferation (4850). A variety of benign stromal tumors may be seen in the breast, including leiomyoma, neurofibroma, myofibroblastoma, and chondrolipoma.

INFLAMMATORY CONDITIONS
FAT NECROSIS Fat necrosis seen in the breast is most commonly iatrogenic. However, on occasion it can mimic breast carcinoma both clinically and on mammography. In the early phase, microscopic examination shows a cavity lined by histiocytes with a

52

Section I Oncology and Oncoplastic Surgery

foamy cytoplasm with a smattering of chronic inammatory cells. With time, foreign-body giant cells appear and the lesion becomes sclerotic and may develop coarse microcalcications, which can be recognized as such by an expert mammographer. MAMMARY DUCT ECTASIA This disease typically presents as an ill-dened mass in the areolar lesion in a perimenopausal woman. The ducts in this region are dilated and associated with chronic inammation. Occasionally, abundant plasma cells are seen (plasma cell mastitis), and this condition has been described as a separate entity (51) but probably represents a variant. It can mimic breast carcinoma (5255). GRANULOMATOUS MASTITIS This is a descriptive term that encompasses different etiologies. Mammary tuberculosis is rare. Sarcoidosis can affect the breasts on occasion and should be diagnosed only when all infectious agents have been excluded (56). Idiopathic granulomatous mastitis may be associated with microabscesses and responds to corticosteroid therapy (51,57).

Figure 5.9. Lobular carcinoma in situ. Lobules are distended with


monomorphic cells with moderate amount of cytoplasm and lowgrade nuclei.

LOBULAR CARCINOMA IN SITU


Foote and Stewart (58) introduced the concept of lobular carcinoma in situ (LCIS) in 1941. They observed that LCIS is a rare, multicentric entity that cannot be identified clinically or on gross examination; the invasive carcinoma that might develop might be either ductal or lobular. Their observations have stood the test of time. LCIS has been reported to have a variable incidence ranging from 0.5 to 3.6 (5962), depending on the cohort studied and diagnostic criteria used. LCIS is more common in younger, premenopausal women, and the mean age of diagnosis is 44 to 46 years. African American women have a tenfold lower incidence of LCIS than White women in the United States (56,63,64). In the mammography era the incidence of LCIS has apparently increased (65). Numerous studies have shown that LCIS is commonly bilateral and multicentric (present in more than one quadrant). The incidence of bilaterality varies from 23% to 69% (66,67), and multicentricity varies from 60% to 85% (6870). LCIS is typically an incidental nding in a breast biopsy done for a mammographically detectable lesion, which may be calcications in adjacent sclerosing adenosis or other proliferative lesions. Calcications are rarely associated with LCIS. A typical case of LCIS shows proliferation of monotonous small cells in lobules, which have a bubbly cytoplasm and bland nuclei and distend acini in lobules and track along ducts (pagetoid spread) (Fig. 5.9). These cells may have mucinous (signet ring), clear, myoid, or mosaic features. Occasionally, the cells have highly atypical nuclei, and this variant is referred to as pleomorphic LCIS. The distinction between ALH and LCIS is quantitative. The monotonous cell proliferation should distend and obliterate the lumen in 50% to 75% of acini of a lobule (61,71). Estrogen receptor (ER) is typically overexpressed in cells of LCIS and Her2/neu is not (72). E-cadherin is a useful marker to distin-

guish lobular and ductal proliferations, as it is preferentially expressed in the latter (73). Most women with LCIS do not develop invasive carcinoma on follow-up. However, LCIS confers a relative risk of development of subsequent carcinoma that varies from 6.9 to 12 (56,6062), which may occur in either breast with equal frequency. These carcinomas are mostly invasive ductal carcinomas. Invasive lobular carcinomas occur in 25% to 37% of patients, which is signicantly higher than the incidence of 5% to 10% seen in the general population. No morphologic or molecular characteristics can accurately predict which cases of LCIS will go on to develop invasive carcinoma. These data suggest that that LCIS is best considered to be a risk factor rather than a precursor of invasive carcinoma. Surgical management of LCIS thus does not aim for negative margins, and radiation therapy has no role in management of LCIS. The National Surgical Adjuvant Breast and Bowel Project (NSABP) prevention trial showed a signicant reduction of subsequent carcinoma with tamoxifen.

DUCTAL CARCINOMA IN SITU


Ductal carcinoma in situ (DCIS) comprises lesions in which the neoplastic growth of ductal cells is restricted to within the ductal system. DCIS is considered to be a direct precursor of invasive carcinoma. The data to support this paradigm come from small series of patients whose biopsies were misclassied as benign and were found to have DCIS on retrospective review. The incidence of carcinoma in these patients varied from 11% to 53% (7476). Unlike LCIS, all the invasive carcinomas occurred in the ipsilateral breast in the vicinity of the biopsy site. Mammographic abnormalities, which commonly show microcalcications, are the most common presentation of DCIS. DCIS may present as a mass with or without nipple discharge. The incidence of DCIS increased 587% from 1973 to 1992 (77). Screening mammography alone cannot account for this dramatic increase.

Chapter 5 Pathology of Breast Disorders

53

Figure 5.10. Micropapillary ductal carcinoma in situ. The ducts


are lined by small papillae without discernible brovascular cores.

The neoplastic cells can show varying degrees of differentiation and architectural patterns. They can involve lobules, and this is referred to as lobular cancerization. The cells may form solid, papillary, micropapillary, clinging, and cribriform patterns. Micropapillary DCIS is more likely to be more multicentric (80%) than other types of DCIS (36%) (78) (Fig. 5.10). Comedo pattern refers to central necrosis in the ducts that are lined by poorly differentiated cells. Comedo DCIS is invariably associated with calcications (Fig. 5.11). Comedo necrosis was the only factor found to correlate with ipsilateral recurrence in a multivariate analysis of nine histologic features of DCIS in retrospective pathologic analysis of patients accrued to NSABP B17 (79). A consensus conference in 1997 suggested that nuclear grade (low, intermediate, and high), necrosis, cell polarization, and architectural patterns be mentioned in all diagnosis of DCIS (80). There can be signicant interobserver discordance among pathologists in classifying DCIS. The lesions at the interface of ADH and low-grade DCIS can be problematic for the most experienced pathologist (8,9,81). The distinction

between LCIS and DCIS can usually be made without difculty. E-cadherin staining is a useful adjunct in difcult cases since it is almost always shows no staining in lobular proliferations (73). Low-grade DCIS tends to be estrogen- and progesterone receptor (ER/PR)-positive (91%) and Her2/neu-negative (18%), while high-grade DCIS is less likely to be receptorpositive (57%) and Her2/neu-positive (69%) (82,83). The biomarker prole of DCIS is likely to be similar to the concurrent invasive carcinoma. The NSABP B-24 trial conclusively showed the efcacy of tamoxifen in reducing recurrence in patients with DCIS. Retrospective analysis of specimens from this trial has shown that the subset that overexpress estrogen receptor have a 50% reduction in recurrence, while estrogen receptornegative DCIS do not show a signicant reduction (84). Tissue sampling is an important consideration in evaluating breast excisions for DCIS. Ideally, the entire specimen should be submitted for microscopic examination. This obviously cannot be done in very large excisions or mastectomy specimens. In these cases exhaustive sampling is recommended. The purpose of extensive sampling is to look for areas of invasion. It should be noted that even when the entire specimen is submitted only a fraction of the tissue is actually examined under the microscope. The presence of undetected invasive carcinoma probably accounts for the small incidence of axillary metastases in cases of reported pure DCIS. All specimens should be assessed for margins. In NSABP B-17, only the presence of a tumor-lled duct in contact with the inked margin was categorized as a positive margin (85). Silverstein et al. showed that quantication of the distance of DCIS from the margin is useful, and 1 cm is deemed to be a negative margin (86). Microinvasion refers to an area of invasion that measures 1 mm. This is a difcult problem for the pathologist since sclerosing lesions and complex architectural patterns in comedo DCIS can mimic microinvasion. Most experts agree that a diagnosis of microinvasion should be rendered only when an unequivocal area of invasion is seen away from lobular and ductal structures. The clinical signicance of microinvasion is unclear because variable criteria and sampling techniques have been used in studies to ascertain its behavior.

PAGETS DISEASE OF THE NIPPLE


James Paget reported the association of eczematous changes in the nipple with underlying mammary carcinoma (87). Pagets disease of the nipple refers to the extension of underlying breast cancer to the skin of the nipple. Clinically, Pagets disease presents as scaling and erythema of the nipple-areola complex. Histologic examination shows carcinoma cells in the epidermis (Fig. 5.12). A diagnosis can be made by scrape cytology or shave or punch biopsy. Ninety-ve percent cases of Pagets disease have an underlying carcinoma, which is invariably of ductal type. Pagets disease is commonly associated with underlying comedo-type DCIS. Immunohistochemical stains are useful to distinguish Pagets disease from melanoma and clear cells of the epidermis (Toker cells). Her2/neu, epithelial membrane antigen, and polyclonal carcinoembryonic antigen are usually expressed in Pagets disease (88,89). Cytokeratin 7 is positive in both Toker cells and Pagets disease.

Figure 5.11. Ductal carcinoma in situ, comedo type. The duct is


lined by poorly differentiated cells with central necrosis.

54

Section I Oncology and Oncoplastic Surgery

Figure 5.12. Pagets disease of the nipple. Large carcinoma cells


are seen in the epidermis.

Figure 5.13. Invasive ductal carcinoma, moderately differentiated. Clusters of moderately differentiated cells inltrate the stroma. With the modied Bloom-Richardson scoring system, the architectural grade is 3, the nuclear grade is 2, and the mitotic rate is 1. The total score is 7 (moderately differentiated).
INVASIVE LOBULAR CARCINOMA Invasive lobular carcinomas (ILCs) account for 5% to 10% of breast carcinomas (9395). The variance in reported incidence and biology of ILC may stem from the criteria used for diagnosis. Lobular carcinomas have been reported to have a higher incidence of being bilateral and multifocal in the ipsilateral breast (96). However, in follow-up studies, the incidence of contralateral cancer has been found to be similar to that of ductal carcinoma (97). ILC presents as a palpable mass or mammographic abnormality. However these features can be subtle, making this entity a diagnostic challenge. The desmoplastic response in ILC is not as prominent as in IDC, and on gross examination the mass may be diffuse and not as gritty as a typical IDC. Histologic examination shows cells similar to those seen in LCIS, which are small and invade the stroma singly and form a single-le pattern in the classic form (Fig. 5.14). These

INVASIVE CARCINOMA
Ductal or no special type (NST) carcinomas are the most common variant and account for 70% to 80% of all breast carcinomas (9092). The special types of mammary carcinoma include lobular, tubular, medullary, and mucinous types and account for the remaining 20% to 30%. To be categorized as such, the overwhelming majority (90%) of the carcinoma should show the special pattern, as this correlates best with their better biological behavior. INVASIVE DUCTAL CARCINOMA/INVASIVE MAMMARY CARCINOMA OF NO SPECIAL TYPE Invasive ductal carcinomas (IDCs) typically present as a palpable mass or mammographic abnormality. Central tumors can cause tethering or inversion of the nipple. Occult carcinomas can present as axillary metastases. Gross examination invariably reveals a hard, speculated mass on cut section. Histologic examination may show atypical cells in myriad patterns, forming glands, ducts, nests, trabeculae, or sheets (Fig. 5.13). Commonly, more than one pattern is seen within the same tumor. The typical gritty nature of the tumor is imparted by the dense desmoplasia in the background. The best way to classify invasive ductal carcinoma in a manner that predicts their biology is by stage and grade. A detailed description of the various patterns does not predict the biology of a carcinoma and is thereby not very useful. Moreover, a tumor invariably has numerous patterns, and these have not been shown to behave any differently than invasive ductal carcinoma. DCIS is commonly associated with invasive carcinoma, and usually the grade of the two is concordant. Well-differentiated carcinomas are typically hormone receptorpositive and Her2/neu-negative, and poorly differentiated tumors have the reverse pattern. Inammatory carcinoma is a term for tumors with extensive involvement of dermal lymphatics, which causes erythema of the overlying skin, mimicking an inammatory process. The underlying carcinoma is usually a diffuse mass.

Figure 5.14. Invasive lobular carcinoma. Cells arranged in single les are seen invading the stroma. The cells have low-grade nuclei and bubbly cytoplasm.

Chapter 5 Pathology of Breast Disorders

55

cells encircle the normal structures of the breast, forming a targetoid pattern. This type is commonly associated with LCIS. The classic lobular carcinomas are typically hormone receptor positive and Her2/neu-negative (98). Other architectural patterns include solid, alveolar, mixed, and tubulolobular types. The pleomorphic variant is composed of cells that are larger and more atypical and behaves more aggressively than the classical variant (99). Signet ring cell variant, with more than 10% of cells showing signet ring features, also has a poor outcome (100). Lobular carcinomas are more likely than IDC to metastasize to leptomeninges, peritoneum, gastrointestinal tract, and reproductive organs. Metastases to lungs, liver, and brain parenchyma are less common (101). Metastasis to the stomach (linitis plastica) and ovary (Krukenbergs tumor) can masquerade as primary tumors of these organs. With conservative therapy, lobular carcinoma has a similar prognosis to that of matched invasive ductal carcinoma (102). INVASIVE TUBULAR CARCINOMA Invasive tubular carcinoma in its pure form seldom metastasizes and has a reported incidence of 1% to 4% of all breast cancers and 7.7% to 27% in mammographically screened populations (103,104). It is typically found as an incidental lesion on screening mammography as a mass lesion and occasionally as microcalcifications (105). Tubular carcinomas are commonly seen in older, postmenopausal women. On gross examination, tubular carcinoma appears not dissimilar to invasive ductal carcinoma. It typically appears as a small (1 cm), scirrhous mass. Microscopic examination shows a carcinoma composed almost entirely (90%) of angulated tubular structures lined by a single layer of cells with low-grade nuclei, with apical snouting (Fig. 5.15). The stroma is desmoplastic. Low-grade DCIS is frequently seen in association with tubular carcinoma. Tubular carcinomas are typically hormone receptor positive and Her2/neu-negative (106). It is important to recognize this variant since it has a good prognosis. Both disease-free survival and overall survival are better in tubular carcinoma, even in the presence of axillary lymph node metastases (107).

INVASIVE CRIBRIFORM CARCINOMA Invasive cribriform carcinoma (ICC) also has an excellent prognosis like tubular carcinoma, and not infrequently the two patterns are intermixed. Mammographically, the tumors may be occult (108). Gross appearance of invasive cribriform carcinoma is similar to that of IDC. Microscopically, the tumor has a cribriform architecture, and typically the cells are low grade. Page et al. (109), dened ICC as a tumor composed entirely of the cribriform pattern or with at least 50% cribriform pattern, with the remainder being tubular carcinoma. Invasive cribriform carcinoma should be differentiated from cribriform DCIS. Invasive carcinoma almost always invokes a desmoplastic response, and the clusters of cells grow haphazardly and are not arranged in a lobular or ductal pattern. Invasive cribriform in its pure form is seldom associated with lymphovascular invasion, and the incidence of axillary metastases is lower in pure ICC. The presence of one or two positive low axillary lymph node metastasis has been reported not to affect overall survival in pure ICC (110). Overall survival for ICC has been reported to be 100% at 5 years and 91% at 10-year follow-up (110,111).

MUCINOUS CARCINOMA Extracellular mucin typifies mucinous carcinoma, which in its pure form, has an excellent prognosis. Older women (seventh decade) are more likely to have mucinous carcinoma, and the pure form presents as a well-circumscribed mass on mammography (112). Gross examination reveals a gelatinous, well-circumscribed mass. Histology reveals extracellular pools of mucin with a few clusters of low-grade cells (Fig. 5.16). The pure form should have this histology in 90% to 100% of the tumor. DCIS is frequently seen in the vicinity. The cells in mucinous carcinoma are typically positive for hormone receptors and negative for Her2/neu (106). Mucinous carcinomas have been seen to have a lower recurrence rate and increased survival rate, especially in the node-negative group (113,114).

Figure 5.15. Tubular carcinoma. The invasive carcinoma is composed entirely of angulated tubules, which are lined by low-grade cells with apical snouts.

Figure 5.16. Mucinous carcinoma. Pools of mucin contains small clusters of well-differentiated cells.

56

Section I Oncology and Oncoplastic Surgery

MEDULLARY CARCINOMA Medullary carcinoma is a paradox, in that it is a poorly differentiated carcinoma but has been reported to have a good prognosis. Medullary carcinoma is common in women with BRCA1 mutations, and this may in part explain the lower mean age of presentation (115). Calcifications are seldom seen with this variant on mammography. Medullary carcinoma is a well-circumscribed eshy mass on gross examination. The criteria for diagnosis of medullary carcinoma include a syncytial growth pattern, dense lymphoplasmacytic inltrate, microscopic circumscription, and lack of ductal differentiation (116). The cells are very poorly differentiated, with clumped chromatin with a high mitotic rate (Fig. 5.17). The tumor pushes the surrounding breast parenchyma instead of invading it. A dense lymphoplasmacytic inltrate is seen in the stroma of the tumor and also around adjacent areas of DCIS and normal lobules. If some but not all of these features are present, then the carcinoma is classied as atypical medullary carcinoma. Medullary carcinoma is commonly overdiagnosed, as these criteria are not adhered to (117). Medullary carcinoma is typically hormone receptornegative (118). Her2/neu overexpression is also uncommon (119). Axillary lymphadenopathy maybe detected clinically, but on histologic examination these lymph nodes are found not to have metastases (120). Axillary metastases occur at a lower rate in medullary carcinoma than in invasive ductal carcinoma (118). Medullary carcinoma has been reported to have a better prognosis; however, these results could not be replicated (118,121). There is considerable discordance among pathologists in applying the diagnostic criteria (122). BASAL-LIKE CARCINOMA DNA microarray proling of breast carcinoma has identied subtypes that have different clinical outcomes. With gene expression proles from an intrinsic set of 534 genes, breast carcinomas have been classied as follows: luminal A (ER), luminal B (ER), Her2/neu overexpressing, normal breast like, and basal-like (123). Basal-like carcinoma has poor prognosis as assessed by relapse-free survival (124). Immunohistochemical assays show that basal-like carcinomas are Her2/neuand estrogen receptornegative but are positive for basal cytok-

eratins and Her1 (125). The cytokeratin prole of this type of carcinoma is similar to that of myoepithelial cells that are basally located, hence the name basal-like. Patients with BRCA1 mutations have a high preponderance of basal-like carcinoma (124).

OTHER TYPES OF INVASIVE CARCINOMA


Other types of invasive carcinoma are rare and account for less than 2% of all breast carcinomas (126). More important, they have not been reliably shown to have a biological behavior that is signicantly different from invasive ductal carcinoma. These variants should be recognized. as they have important clinical characteristics. Invasive papillary carcinoma are common in postmenopausal, non-White women and present as a nodular mass (127). Microscopically, the tumor is circumscribed and is composed of delicate papillary fronds lined by cells with intermediate nuclei, associated with microcalcications. These tumors are usually hormone receptorpositive and have been reported to have a good prognosis (113,127). Invasive micropapillary carcinoma occurs at a mean age of 51 to 62 years. The mean size varies from 2 to 4.2 cm, and 33% to 67% tumors show grade III histology. Most invasive papillary carcinomas are associated with DCIS. Microscopically, the tumor is composed of small clusters of cells in clear spaces. Lymphovascular invasion has been reported in 15% to 71% cases. Limited follow-up studies are available, and the prognosis depends largely on stage, grade, and receptor status (128). Metaplastic carcinoma represent a heterogeneous group of tumors in which the ductal components of the tumor have transformed into other epithelial or mesenchymal elements. The most common metaplasia is to squamous differentiation. Some tumors show heterologous differentiation to mesenchymal elements, of which chondroid or osseous differentiation is most common. Metaplastic carcinoma tend to be hormone receptor negative. Prognosis of these tumors is similar to that of invasive ductal carcinoma (129). Adenoid cystic carcinoma in the breast has a good prognosis, as opposed to its biological behavior in the salivary glands (130). The histology is identical to that of the tumor commonly seen in the salivary glands. The tumor is cells are small and monomorphic and are typically arranged in a cribriform or trabecular pattern with intraluminal basement membrane material. Secretory carcinoma are well circumscribed, small, and of low grade and have a glandular architecture lled with eosinophilic secretions. Usually, hormone receptors are positive in secretory carcinoma.

PROGNOSTIC AND PREDICTIVE FACTORS OF INVASIVE CARCINOMA


Prognostic factors refer to features of the tumor that correlate with the natural history of the disease in the absence of systemic adjuvant therapy. Predictive factors are any measures associated with response or lack of response to a particular therapy (131). AXILLARY NODAL STATUS

Figure 5.17. Medullary carcinoma. Poorly differentiated cells are


arranged in sheets, interspersed by dense lymphoplasmacytic inltrate.

Metastasis to the axillary lymph nodes is the most powerful prognostic factor for breast carcinoma. Node-negative patients have 70% to 80% 10-year disease-free survival (DFS), while

Chapter 5 Pathology of Breast Disorders

57

patients with one to three positive nodes have approximately 60% DFS, and patients with four or more positive nodes only have 30% to 40% DFS at 10 years. Larger tumors are more likely to have lymph node metastases. Standard evaluation of the axillary lymph nodes should include a minimum of ten lymph nodes. Lymph node dissection is associated with signicant morbidity. The sentinel lymph node (SLN) is the first draining lymph node of a tumor, and its examination has become a good surrogate for axillary lymph node dissection. Numerous studies have compared SLN to axillary lymph node dissection with a false-negative rate between 5% and 10%. Immunohistochemistry for cytokeratin can identify single cells, which may not have been discerned on routine microscopy. The American Joint Committee on Cancer (AJCC) included these factors in the latest staging system for breast cancer (132). The new classication classies all metastases less than 0.2 mm, either by routine microscopy or immunohistochemistry, as pN0(i). Metastases greater than 0.2 mm but less than 2 mm are categorized as pN1(mi). Nodal staging based entirely on sentinel lymph node is designated as (sn). The equivalence of SLN to axillary lymph node dissection is being tested by two prospective clinical trials (American College of Surgeons Oncology Group [ACOSOG] Z0011 and NSABP B-31). TUMOR SIZE Carter et al. reported data from 24,740 cases in the Surveillance, Epidemiology and End Results Program that showed a linear relationship between tumor size and survival and tumor size and lymph node metastases (133). Patients with tumors 1 cm in size had 12% DFS at 20-year follow-up (134). However, systemic therapy is useful even in this cohort. Extremely large tumors may have better outcomes (135). The AJCC staging system denes tumor size as the measurement of only invasive carcinoma. For tumors for which a whole cross section can be represented on one slide, size estimation is a relatively simple exercise. Vigorous biopsy techniques can make size estimation of small tumors problematic. HISTOLOGIC GRADE The Elston and Ellis modication of the Bloom and Richardson grading scheme has been endorsed both by the College of American Pathologists and the AJCC Cancer Staging Manual (136). This system assigns a score of 1 to 3 each to gland formation (architecture), mitotic activity (proliferation), and nuclear pleomorphism (cellular differentiation). A tumor with a total score of 3 to 5 is categorized as grade 1, one with a score of 6 or 7 as grade 2, and one with a score of 8 or 9 as grade 3. This score correlates well with relapse-free survival and overall survival. This system also has signicant interobserver agreement (137). HISTOLOGIC SUBTYPE Special types of breast carcinoma are discussed elsewhere in this chapter. Tubular, mucinous, cribriform, and adenoid cystic carcinoma have a very good prognosis. Strict criteria should be used to make these diagnoses. HORMONE RECEPTORS Estrogen and progesterone receptors are both prognostic and predictive factors. They are typically expressed in well-differentiated tumors and are inversely correlated with proliferation

Figure 5.18. Estrogen receptor immunohistochemistry. Cells of invasive lobular carcinoma show strong nuclear staining.
indices. Immunohistochemical assays are routinely used to assess the receptor status (Fig. 5.18). They are mainly used as predictive factors for hormonal therapy. American Society of Clinical Oncology and College of American Pathologists (ASCO/CAP) have recently published guidelines for immunohistochemical testing of ER and PR in breast cancer (138). An Early Breast Cancer Trialists Collaborative Group overview of tamoxifen trials showed good correlation between ER status and response to treatment (139). There is a 40% to 50% annual reduction of DFS in patients with ER-positive tumors, and this is not observed with ER-negative tumors. Progesterone receptor is not as powerful a predictive factor. Many tumors that initially respond to hormonal therapy develop secondary resistance. Aromatase inhibitors have been shown to be more effective than tamoxifen in postmenopausal women (140). HER2/NEU Her2/neu is a proto-oncogene and is amplied in 10% to 34% breast cancers. Her2/neu amplication is commonly seen in highgrade tumors. Immunohistochemistry is routinely used to assess overexpression (Fig. 5.19); however, a central review of community-based immunohistochemical assays showed signicant discrepancy in 18% of cases (141). ASCO/CAP have published guideline recommendations for Her2 testing in an attempt to enhance quality of testing and decrease inter-laboratory variation (142). The prognostic signicance of Her2/neu is most important in node-positive patients. Her2/neu overexpression predicts poor response to cyclophosphamide, methotrexate, and uorouracil (CMF)based chemotherapy (143). Her2/neu overexpression may also be associated with resistance to hormonal therapy (140). The humanized murine monoclonal antibody to Her2/neu, trastuzumab (Herceptin), in combination with chemotherapy has shown improved DFS in patients who overexpress Her2/neu. PROLIFERATION INDEX Proliferative activity can be assessed by numerous means, the simplest of which is mitotic index. Other methods include S phase fraction (SPF) by DNA ow cytometry, thymidine labeling index, bromodeoxyuridine index, and immunohistochemistry for Ki-67. Mitotic index refers to the number of mitotic gures seen

58

Section I Oncology and Oncoplastic Surgery

MOLECULAR CLASSIFICATION OF BREAST CANCER DNA microarray studies of an intrinsic gene list of 496 genes have been used to classify breast cancer into distinct subtypes (150). These intrinsic subtypes include two estrogen receptor positive categories (luminal A and luminal B) and two estrogen receptornegative categories (basal-like and Her2-positive). Luminal A tumors express high levels of ER and GATA3 genes and have a good prognosis (123,124,151). Luminal B tumors have low to moderate expression of luminal-specic genes and also express human epidermal growth factor receptor-1 (Her1), Her2, and/or cyclin E1 (123,124). P53 is more frequently mutated in luminal B subtype. The Her2 subtype may be ER or ER. The Her2/ER tumors typically cluster near the basal-like tumors. Basal-like tumors have low expression of Her2, ER, and progesterone receptor (PR) and high expression of basal epithelial cell layer (cytokeratins 5, 6, and 17) (150). Luminal A and B tumors are ER-positive and have low to intermediate histologic grade, and basal-like cancers are ER-negative and have high histologic grade (91%) (152). Breast cancers with triple-negative (ER/PR/Her2) phenotype as assessed by immunohistochemistry cluster with basal-like genotype; however, basal-like cancers have several other subgroups (125,152). In the clinical setting basal-like and triple-negative are often used synonymously since breast cancers are routinely assessed by immunohistochemistry for ER, PR, and Her2. This immunohistochemical prole is also being used to categorize basal-like tumors in prospective clinical trials. Triple-negative breast cancers are commonly seen in younger women and those of African descent and have a poor prognosis with a predilection for visceral metastases. Basal-like breast cancers usually have a very high rate of proliferation and are sensitive to chemotherapy. In a phase II study of women with metastatic triple-negative breast cancer, patients treated with the investigational poly-ADP-ribose polymerase-1 inhibitor BSI-201 in combination with standard gemcitabine and carboplatin chemotherapy had signicantly better outcomes than women who received standard chemotherapy alone (153). Other targeted agents, including epidermal growth factor receptor and vascular endothelial growth factor, are also currently in clinical trials. PROGNOSTIC AND PREDICTIVE MULTIGENE PREDICTORS A plethora of multigene predictors have entered the market place in recent years. These assays use immunohistochemistry, uorescent in situ hybridization, real-time polymerase chain reaction (RT-PCR), and genomic microarray profiling. Two multigene predictors, Oncotype Dx and MammaPrint, have gained widespread acceptance. Oncotype Dx (Genomic Health, Inc., Redwood City, CA) uses genomic analysis by RT-PCR to prognosticate breast carcinoma (154). The assay is performed on RNA extracted from formalin-fixed, paraffin-embedded (FFPE) tissue. Sixteen cancer-related genes and 5 reference genes are assessed, and a recurrence score (RS) is generated (17, low risk; 18 to 30, intermediate risk; 30, high risk). Samples from NSABP B-14 were tested, and the assay accurately predicted the risk of distant recurrence in hormone receptorpositive, lymph nodenegative patients who were treated with tamoxifen (154). These cohorts mostly included women

Figure 5.19. Her2/neu immunohistochemistry. Strong membranous staining is seen in invasive ductal carcinoma.

in a dened area, which is typically ten high-power elds. Mitotic index is an integral part of the modied Bloom-Richardson scoring system. Mitotic index has been shown to correlate with clinical outcome in multivariate analysis and clinical trials (144). Mitotic index also has good reproducibility among pathologists (145). Proliferation is easily assessed by immunohistochemistry with Ki-67. Proliferation index refers to the percentage of positive cells in a given area, which should include at least 200 cells. Immunohistochemistry for Ki-67 can easily be done on parafn sections. Univariate and multivariate analyses have shown signicance of proliferative index as a marker for DFS and overall survival (146). Some studies have not found a positive correlation. This may be due to varying techniques and cutoffs. The SPF is found by ow cytometry, which determines which cells are in the S phase and also DNA ploidy. Elevated SPF correlates with high grade. SPF correlates with DFS and OS for both nodenegative and node-positive patients. In multivariate analysis, when tumor grade is included, SPF may lose its signicance (147). SPF is technically challenging, as it requires fresh tissue. This maybe difcult for very small lesions, and it is also not possible to be certain whether cells from invasive or in situ components are being analyzed. These issues are increasingly important as radiologic techniques enhance the ability to diagnose minute lesions. Immunohistochemistry for Ki-67 does not have these drawbacks and is routinely used in our laboratory. LYMPHOVASCULAR INVASION Carcinoma cells are seen in peritumoral lymphatics, and this is referred to as lymphatic invasion. It is critical that shrinkage artifact, which is seen as spaces around clusters of cells, not be interpreted as lymphatic invasion. Diagnosis of lymphatic invasion should be made only when neoplastic cells are seen in a vessel lined by endothelial cells in the peritumoral region, to avoid overinterpretation. Lymphatic invasion is most useful as a prognostic factor in node-negative patients, as it indicates risk of axillary node involvement (148). It is an indicator of poor prognosis in node-positive patients (149). Some studies have not found this correlation, and the variance in the clinical signicance of lymphatic invasion may partly be explained by the criteria used by pathologists for diagnosis.

Chapter 5 Pathology of Breast Disorders

59

greater than 40 years of age. Oncotype DX analysis of samples from the NSABP B-20 showed that patients with a low or intermediate RS benet the most from tamoxifen, and chemotherapy was most effective in patients with high RS (155). This retrospective analysis was limited by the fact that RS was developed using samples from NSABP B-20 and the patients on the chemotherapy arm also received tamoxifen. Oncotype DX has also been shown to be predictive in lymph nodepositive patients: Patients with high RS have the most benefit from chemotherapy (156). A prospective trial in which therapy is guided by the RS has been sponsored by the North American Breast Cancer Intergroup. The objective of the TAILORx Clinical Trial is to determine whether chemotherapy benefits patients with intermediate RS (RS 11 to 25). Patients with RS 11 to 25 are randomized to either hormonal therapy alone or hormonal therapy and chemotherapy. Oncotype Dx has gained widespread acceptance in the United States, and the cost of the test is covered by most providers. MammaPrint (Agendia BV, Amsterdam, Netherlands) is a microarray-based test that has been approved by the U.S. Food and Drug Administration as a prognostic assay for 61-year-old women with ER-positive or ER-negative, lymph nodenegative breast cancer (157). The test requires fresh tissue in an RNA preservative or frozen samples and cannot be performed on samples. The 70 genes included in the test focus on proliferation, invasion, metastasis, stromal integrity, and angiogenesis. The test classies patients as having high or low risk and has been validated in the TANSBIG Consortium of European cancer centers (158). A prospective trial (the MINDACT trial), sponsored by European Organization for Research and Treatment of Cancer, uses MammaPrint and standard clinicopathologic factors to categorize patients as high or low risk. Patients with concordant MammaPrint score and clinicopathologic characteristics get either chemotherapy (high risk) or hormonal therapy (low risk). Cases with discordant MammaPrint score and clinicopathologic characteristics are randomized to treatment based on genomic or the clinicopathologic characteristics (159).

outcome. Dupont and Page contributed greatly to our understanding of benign breast disease and established that the majority of brocystic changes are not associated with a higher-than-average risk of developing breast cancer. The distinction between prognostic factors and predictive factors becomes more critical as new biomarkers and targeted therapies become available. The ER status is an example of both. ER-positive tumors have a better prognosis, and the presence of an ER also predicts a benecial response to antiestrogen therapy. The Oncotype DX assay is the rst clinically available genomic analysis. This technology is currently validated in a specic patient population, but it is expected that similar analyses will allow for expanded use in other groups to further characterize biological behavior and more specic targeted therapy. S.C.W.

REFERENCES
1. Dupont WD, Page DL. Risk factors for breast cancer in women with proliferative breast disease. N Engl J Med 1985;312(3):146151. 2. Page DL, Dupont WD, Rogers LW, et al. Atypical hyperplastic lesions of the female breast. A long-term follow-up study. Cancer 1985;55(11):26982708. 3. Is brocystic disease of the breast precancerous? A consensus report from the College of American Pathologists. Indiana Med 1986;79(9):753754. 4. London SJ, Connolly JL, Schnitt SJ, et al. A prospective study of benign breast disease and the risk of breast cancer. JAMA 1992;267(7):941944. 5. Bloodgood J. The pathology of chronic cystic mastitis of the female breast, with special consideration of the blue-domed cyst. Arch Surg 1921;3:445. 6. Haagensen CD. The relationship of gross cystic disease of the breast and carcinoma. Ann Surg 1977;185(3):375376. 7. Jensen RA, Page DL, Dupont WD, et al. Invasive breast cancer risk in women with sclerosing adenosis. Cancer 1989;64(10):19771983. 8. Rosai J. Borderline epithelial lesions of the breast. Am J Surg Pathol 1991;15(3):209221. 9. Schnitt SJ, Connolly JL, Tavassoli FA, et al. Interobserver reproducibility in the diagnosis of ductal proliferative breast lesions using standardized criteria. Am J Surg Pathol 1992;16(12):11331143. 10. Bodian CA, Perzin KH, Lattes R, et al. Reproducibility and validity of pathologic classications of benign breast disease and implications for clinical applications. Cancer 1993;71(12):39083913. 11. Page DL, Schuyler PA, Dupont WD, et al. Atypical lobular hyperplasia as a unilateral predictor of breast cancer risk: a retrospective cohort study. Lancet 2003;361(9352):125129. 12. Page DL, Dupont WD, Rogers LW. Ductal involvement by cells of atypical lobular hyperplasia in the breast: a long-term follow-up study of cancer risk. Hum Pathol 1988;19(2): 201207. 13. Marshall LM, Hunter DJ, Connolly JL, et al. Risk of breast cancer associated with atypical hyperplasia of lobular and ductal types. Cancer Epidemiol Biomarkers Prev 1997;6(5): 297301. 14. Page DL. Breast lesions, pathology and cancer risk. Breast J 2004;10(Suppl 1):S3S4. 15. Hartmann LC, Sellers TA, Frost MH, et al. Benign breast disease and the risk of breast cancer. N Engl J Med 2005;353(3):229237. 16. Collins LC, Achacoso NA, Nekhlyudov L, et al. Clinical and pathologic features of ductal carcinoma in situ associated with the presence of at epithelial atypia: an analysis of 543 patients. Mod Pathol 2007;20(11):11491155. 17. Tan PH, Ho BC, Selvarajan S, et al. Pathological diagnosis of columnar cell lesions of the breast: are there issues of reproducibility? J Clin Pathol 2005;58(7):705709. 18. Brem RF, Behrndt VS, Sanow L, et al. Atypical ductal hyperplasia: histologic underestimation of carcinoma in tissue harvested from impalpable breast lesions using 11-gauge stereotactically guided directional vacuum-assisted biopsy. AJR Am J Roentgenol 1999; 172(5):14051407. 19. Moore MM, Hargett CW III, Hanks JB, et al. Association of breast cancer with the nding of atypical ductal hyperplasia at core breast biopsy. Ann Surg 1997;225(6):726731; discussion 731733. 20. Gadzala DE, Cederbom GJ, Bolton JS, et al. Appropriate management of atypical ductal hyperplasia diagnosed by stereotactic core needle breast biopsy. Ann Surg Oncol 1997;4(4):283286. 21. Burbank F. Stereotactic breast biopsy of atypical ductal hyperplasia and ductal carcinoma in situ lesions: improved accuracy with directional, vacuum-assisted biopsy. Radiology 1997;202(3):843847. 22. Lehman CD, Gatsonis C, Kuhl CK, et al. MRI evaluation of the contralateral breast in women with recently diagnosed breast cancer. N Engl J Med 2007;356(13):12951303. 23. Perkins C, Balma D, Garcia R, et al. Why current breast pathology practices must be evaluated. A Susan G. Komen for the Cure White Paper: June 2006. Breast J 2007;13(5): 443447.

EDITORIAL COMMENTS The breast pathologists responsibility is daunting. Based on histologic morphology and biomarkers, clinicians use the ndings to predict the biological behavior of a tumor and tailor treatment to the individual. Both physicians and patients scrutinize the pathology report to extract all available information from it. Education of patients about those situations in which the pathology diagnosis may be open to interpretation or require a more exhaustive examination of the tissue is important. Interesting studies have been conducted that demonstrate signicant interobserver variability, thus highlighting that histologic appearance is not black and white, but a continuum from benign to malignant, with atypia and cell of origin sometimes representing the most challenging cases. The future holds the possibility of creating a genetic map through gene array analysis of an individual tumor so there is an irrefutable signature of the cell of origin. Dr. Singh gives us an excellent review of both benign and malignant breast disease, with a focus on clinical

60

Section I Oncology and Oncoplastic Surgery


67. Ringberg A, Palmer B, Linell F. The contralateral breast at reconstructive surgery after breast cancer operationa histopathological study. Breast Cancer Res Treat 1982;2(2):151161. 68. Andersen JA. Multicentric and bilateral appearance of lobular carcinoma in situ of the breast. Acta Pathol Microbiol Scand A 1974;82:730734. 69. Beneld JR, Fingerhut AG, Warner NE. Lobular carcinoma of the breast1969. A therapeutic proposal. Arch Surg 1969;99(2):129140. 70. Warner NE. Lobular carcinoma of the breast. Cancer 1969;23(4):840846. 71. Rosen P. Rosens Breast Pathology. Philadelphia, PA: Lippincott Williams & Wilkins; 2001. 72. Albonico G, Querzoli P, Ferretti S, et al. Biological prole of in situ breast cancer investigated by immunohistochemical technique. Cancer Detect Prev 1998;22(4):313318. 73. Moll R, Mitze M, Frixen UH, et al. Differential loss of E-cadherin expression in inltrating ductal and lobular breast carcinomas. Am J Pathol 1993;143(6):17311742. 74. Page DL, Dupont WD, Rogers LW, et al. Intraductal carcinoma of the breast: follow-up after biopsy only. Cancer 1982;49(4):751758. 75. Rosen PP, Braun DW Jr, Kinne DE. The clinical signicance of pre-invasive breast carcinoma. Cancer 1980;46(4 suppl):919925. 76. Eusebi V, Foschini MP, Cook MG, et al. Long-term follow-up of in situ carcinoma of the breast with special emphasis on clinging carcinoma. Semin Diagn Pathol 1989;6(2):165173. 77. Ernster VL, Barclay J, Kerlikowske K, et al. Incidence of and treatment for ductal carcinoma in situ of the breast. JAMA 1996;275(12):913918. 78. Patchefsky AS, Schwartz GF, Finkelstein SD, et al. Heterogeneity of intraductal carcinoma of the breast. Cancer 1989;63(4):731741. 79. Fisher ER, Dignam J, Tan-Chiu E, et al. Pathologic ndings from the National Surgical Adjuvant Breast Project (NSABP) eight-year update of protocol B-17: intraductal carcinoma. Cancer 1999;86(3):429438. 80. Consensus Conference Committee. Consensus Conference on the Classication of Ductal Carcinoma in Situ, April 2528, 1997. Cancer 1997;80:17981802. 81. Chen WY, Hankinson SE, Schnitt SJ, et al. Association of hormone replacement therapy to estrogen and progesterone receptor status in invasive breast carcinoma. Cancer 2004;101(7):14901500. 82. Bur ME, Zimarowski MJ, Schnitt SJ, et al. Estrogen receptor immunohistochemistry in carcinoma in situ of the breast. Cancer 1992;69(5):11741181. 83. Ho GH, Calvano JE, Bisogna M, et al. In microdissected ductal carcinoma in situ, HER-2/ neu amplification, but not p53 mutation, is associated with high nuclear grade and comedo histology. Cancer 2000;89(11):21532160. 84. Allred C, Bryant J, Land S, et al. Estrogen receptor expression as a predictive marker of the effectiveness of tamoxifen in the treatment of DCIS: ndings from NSABP protocol B-24 [Abstract 31]. Breast Cancer Res Treat 2002;76(11):S36. 85. Fisher B, Dignam J, Wolmark N, et al. Lumpectomy and radiation therapy for the treatment of intraductal breast cancer: ndings from National Surgical Adjuvant Breast and Bowel Project B-17. J Clin Oncol 1998;16(2):441452. 86. Silverstein MJ, Gierson ED, Colburn WJ, et al. Can intraductal breast carcinoma be excised completely by local excision? Clinical and pathologic predictors. Cancer 1994;73(12):29852989. 87. Paget J. On disease of the mammary areola preceding cancer of the mammary gland. St Bartholomew Hosp Rep 1874;10:8789. 88. Marucci G, Betts CM, Golouh R, et al. Toker cells are probably precursors of Paget cell carcinoma: a morphological and ultrastructural description. Virchows Arch 2002;441(2):117123. 89. Manavi M, Hudelist G, Schatten C, et al. Characteristics of clear cells and Toker cells in the epidermis of underlying nipple duct adenoma. Anticancer Res 2002;22(6B):36913700. 90. Anderson TJ, Lamb J, Alexander F, et al. Comparative pathology of prevalent and incident cancers detected by breast screening. Edinburgh Breast Screening Project. Lancet 1986;1(8480):519523. 91. Anderson TJ, Lamb J, Donnan P, et al. Comparative pathology of breast cancer in a randomised trial of screening. Br J Cancer 1991;64(1):108113. 92. Patchefsky AS, Shaber GS, Schwartz GF, et al. The pathology of breast cancer detected by mass population screening. Cancer 1977;40(4):16591670. 93. Fisher ER, Gregorio RM, Fisher B, et al. The pathology of invasive breast cancer. A syllabus derived from ndings of the National Surgical Adjuvant Breast Project (protocol no. 4). Cancer 1975;36(1):185. 94. Rosen PP. The pathological classication of human mammary carcinoma: past, present and future. Ann Clin Lab Sci 1979;9(2):144156. 95. Haagensen C. Diseases of the Breast. 2nd ed. Philadelphia, PA: WB Saunders; 1971. 96. Dixon JM, Anderson TJ, Page DL, et al. Infiltrating lobular carcinoma of the breast. Histopathology 1982;6(2):149161. 97. Schnitt SJ, Connolly JL, Recht A, et al. Inuence of inltrating lobular histology on local tumor control in breast cancer patients treated with conservative surgery and radiotherapy. Cancer 1989;64(2):448454. 98. Porter PL, Garcia R, Moe R, et al. C-erbB-2 oncogene protein in in situ and invasive lobular breast neoplasia. Cancer 1991;68(2):331334. 99. Bentz JS, Yassa N, Clayton F. Pleomorphic lobular carcinoma of the breast: clinicopathologic features of 12 cases. Mod Pathol 1998;11(9):814822. 100. Frost AR, Terahata S, Yeh IT, et al. The signicance of signet ring cells in inltrating lobular carcinoma of the breast. Arch Pathol Lab Med 1995;119(1):6468. 101. Borst MJ, Ingold JA. Metastatic patterns of invasive lobular versus invasive ductal carcinoma of the breast. Surgery 1993;114(4):637641; discussion 641642. 102. Schnitt S. Morphologic risk factors for local recurrence in patients with invasive breast cancer treated with conservative surgery and radiation therapy. Breast J 1997;3:261. 103. Rajakariar R, Walker RA. Pathological and biological features of mammographically detected invasive breast carcinomas. Br J Cancer 1995;71(1):150154. 104. McBoyle MF, Razek HA, Carter JL, et al. Tubular carcinoma of the breast: an institutional review. Am Surg 1997;63(7):639644; discussion 644645. 105. Elson BC, Helvie MA, Frank TS, et al. Tubular carcinoma of the breast: mode of presentation, mammographic appearance, and frequency of nodal metastases. AJR Am J Roentgenol 1993;161(6):11731176.

24. Jacobs TW, Byrne C, Colditz G, et al. Radial scars in benign breast-biopsy specimens and the risk of breast cancer. N Engl J Med 1999;340(6):430436. 25. Dent DM, Cant PJ. Fibroadenoma. World J Surg 1989;13(6):706710. 26. Pike AM, Oberman HA. Juvenile (cellular) adenobromas. A clinicopathologic study. Am J Surg Pathol 1985;9(10):730736. 27. Hertel BF, Zaloudek C, Kempson RL. Breast adenomas. Cancer 1976;37(6):28912905. 28. Dupont WD, Page DL, Parl FF, et al. Long-term risk of breast cancer in women with broadenoma. N Engl J Med 1994;331(1):1015. 29. Schnitt S, Connolly JL. Pathology of Benign Breast Disorders in Diseases of Breast . 2nd ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2000. 30. Page DL, Salhany KE, Jensen RA, et al. Subsequent breast carcinoma risk after biopsy with atypia in a breast papilloma. Cancer 1996;78(2):258266. 31. Azzopardi JG. Problems in Breast Pathology. Philadelphia, PA: WB Saunders; 1979. 32. Kraus FT, Neubecker RD. The differential diagnosis of papillary lesions of the breast. Cancer 1962(144):444. 33. Norris HJ, Taylor HB. Relationship of histologic features to behavior of cystosarcoma phyllodes. Analysis of ninety-four cases. Cancer 1967;20(12):20902099. 34. Page D, Anderson TJ, Johnson RL. Sarcomas of the Breast. Edinburgh, UK: Churchill Livingstone; 1987. 35. Hajdu SI, Espinosa MH, Robbins GF. Recurrent cystosarcoma phyllodes: a clinicopathologic study of 32 cases. Cancer 1976;38(3):14021406. 36. Lindquist KD, van Heerden JA, Weiland LH, et al. Recurrent and metastatic cystosarcoma phyllodes. Am J Surg 1982;144(3):341343. 37. Rosen PP, Caicco JA. Florid papillomatosis of the nipple. A study of 51 patients, including nine with mammary carcinoma. Am J Surg Pathol 1986;10(2):87101. 38. Gudjonsdottir A, Hagerstrand I, Ostberg G. Adenoma of the nipple with carcinomatous development. Acta Pathol Microbiol Scand A 1971;79(6):676680. 39. James BA, Cranor ML, Rosen PP. Carcinoma of the breast arising in microglandular adenosis. Am J Clin Pathol 1993;100(5):507513. 40. Joshi MG, Lee AK, Pedersen CA, et al. The role of immunocytochemical markers in the differential diagnosis of proliferative and neoplastic lesions of the breast. Mod Pathol 1996;9(1):5762. 41. Acs G, Simpson JF, Bleiweiss IJ, et al. Microglandular adenosis with transition into adenoid cystic carcinoma of the breast. Am J Surg Pathol 2003;27(8):10521060. 42. Resetkova E, Flanders DJ, Rosen PP. Ten-year follow-up of mammary carcinoma arising in microglandular adenosis treated with breast conservation. Arch Pathol Lab Med 2003;127(1):7780. 43. Rosen Y, Papasozomenos SC, Gardner B. Fibromatosis of the breast. Cancer 1978;41(4): 14091413. 44. Rosen PP, Ernsberger D. Mammary bromatosis. A benign spindle-cell tumor with significant risk for local recurrence. Cancer 1989;63(7):13631369. 45. Ali M, Fayemi AO, Braun EV, et al. Fibromatosis of the breast. Am J Surg Pathol 1979;3(6):501505. 46. Hanna WM, Jambrosic J, Fish E. Aggressive bromatosis of the breast. Arch Pathol Lab Med 1985;109(3):260262. 47. Rosen PP. Mucocele-like tumors of the breast. Am J Surg Pathol 1986;10(7):464469. 48. Vuitch MF, Rosen PP, Erlandson RA. Pseudoangiomatous hyperplasia of mammary stroma. Hum Pathol 1986;17(2):185191. 49. Powell CM, Cranor ML, Rosen PP. Pseudoangiomatous stromal hyperplasia (PASH). A mammary stromal tumor with myobroblastic differentiation. Am J Surg Pathol 1995;19(3): 270277. 50. Cohen MA, Morris EA, Rosen PP, et al. Pseudoangiomatous stromal hyperplasia: mammographic, sonographic, and clinical patterns. Radiology 1996;198(1):117120. 51. Fletcher A, Magrath IM, Riddell RH, et al. Granulomatous mastitis: a report of seven cases. J Clin Pathol 1982;35(9):941945. 52. Dixon JM, Anderson TJ, Lumsden AB, et al. Mammary duct ectasia. Br J Surg 1983;70(10): 601603. 53. Bundred NJ, Dixon JM, Lumsden AB, et al. Are the lesions of duct ectasia sterile? Br J Surg 1985;72(10):844845. 54. Dixon JM. Periductal mastitis/duct ectasia. World J Surg 1989;13(6):715720. 55. Dixon JM, Ravisekar O, Chetty U, et al. Periductal mastitis and duct ectasia: different conditions with different aetiologies. Br J Surg 1996;83(6):820822. 56. Rosen PP, Kosloff C, Lieberman PH, et al. Lobular carcinoma in situ of the breast. Detailed analysis of 99 patients with average follow-up of 24 years. Am J Surg Pathol 1978;2(3):225251. 57. DeHertogh DA, Rossof AH, Harris AA, et al. Prednisone management of granulomatous mastitis. N Engl J Med 1980;303(14):799800. 58. Foote FWJ, Stewart FW. Lobular carcinoma in situ: a rare form of mammary carcinoma. Am J Pathol 1941;17:491. 59. Wheeler JE, Enterline HT, Roseman JM, et al. Lobular carcinoma in situ of the breast. Long-term followup. Cancer 1974;34(3):554563. 60. Andersen JA. Lobular carcinoma in situ of the breast. An approach to rational treatment. Cancer 1977;39(6):25972602. 61. Page DL, Kidd TE Jr, Dupont WD, et al. Lobular neoplasia of the breast: higher risk for subsequent invasive cancer predicted by more extensive disease. Hum Pathol 1991;22(12): 12321239. 62. Haagensen C, Bodian C, Haagensen DE. Lobular Neoplasia (Lobular Carcinoma in Situ) Breast Carcinoma: Risk and Detection. Philadelphia, PA: WB Saunders; 1981. 63. Newman W. In situ lobular carcinoma of the breast: report of 26 women with 32 cancers. Ann Surg 1963;157:591599. 64. Rosner D, Bedwani RN, Vana J, et al. Noninvasive breast carcinoma: results of a national survey by the American College of Surgeons. Ann Surg 1980;192(2):139147. 65. Frykberg ER, Bland KI. In situ breast carcinoma. Adv Surg 1993;26:2972. 66. Barnes JP. Bilateral lobular carcinoma in situ of the breast; report of 2 cases. Tex State J Med 1959;55(7):581584.

Chapter 5 Pathology of Breast Disorders


106. Diab SG, Clark GM, Osborne CK, et al. Tumor characteristics and clinical outcome of tubular and mucinous breast carcinomas. J Clin Oncol 1999;17(5):14421448. 107. Winchester DJ, Sahin AA, Tucker SL, et al. Tubular carcinoma of the breast. Predicting axillary nodal metastases and recurrence. Ann Surg 1996;223(3):342347. 108. Stutz JA, Evans AJ, Pinder S, et al. The radiological appearances of invasive cribriform carcinoma of the breast. Nottingham Breast Team. Clin Radiol 1994;49(10):693695. 109. Page DL, Dixon JM, Anderson TJ, et al. Invasive cribriform carcinoma of the breast. Histopathology 1983;7(4):525536. 110. Venable JG, Schwartz AM, Silverberg SG. Inltrating cribriform carcinoma of the breast: a distinctive clinicopathologic entity. Hum Pathol 1990;21(3):333338. 111. Ellis IO, Galea M, Broughton N, et al. Pathological prognostic factors in breast cancer. II. Histological type. Relationship with survival in a large study with long-term follow-up. Histopathology 1992;20(6):479489. 112. Wilson TE, Helvie MA, Oberman HA, et al. Pure and mixed mucinous carcinoma of the breast: pathologic basis for differences in mammographic appearance. AJR Am J Roentgenol 1995;165(2):285289. 113. Fisher ER, Anderson S, Redmond C, et al. Pathologic ndings from the National Surgical Adjuvant Breast Project protocol B-06. 10-year pathologic and clinical prognostic discriminants. Cancer 1993;71(8):25072514. 114. Avisar E, Khan MA, Axelrod D, et al. Pure mucinous carcinoma of the breast: a clinicopathologic correlation study. Ann Surg Oncol 1998;5(5):447451. 115. Eisinger F, Jacquemier J, Charpin C, et al. Mutations at BRCA1: the medullary breast carcinoma revisited. Cancer Res 1998;58(8):15881592. 116. Ridol RL, Rosen PP, Port A, et al. Medullary carcinoma of the breast: a clinicopathologic study with 10 year follow-up. Cancer 1977;40(4):13651385. 117. Rubens JR, Lewandrowski KB, Kopans DB, et al. Medullary carcinoma of the breast. Overdiagnosis of a prognostically favorable neoplasm. Arch Surg 1990;125(5):601604. 118. Pedersen L, Zedeler K, Holck S, et al. Medullary carcinoma of the breast. Prevalence and prognostic importance of classical risk factors in breast cancer. Eur J Cancer 1995;31A(1314): 22892295. 119. Somerville JE, Clarke LA, Biggart JD. c-erbB-2 overexpression and histological type of in situ and invasive breast carcinoma. J Clin Pathol 1992;45(1):1620. 120. Neuman ML, Homer MJ. Association of medullary carcinoma with reactive axillary adenopathy. AJR Am J Roentgenol 1996;167(1):185186. 121. Rapin V, Contesso G, Mouriesse H, et al. Medullary breast carcinoma. A reevaluation of 95 cases of breast cancer with inammatory stroma. Cancer 1988;61(12):25032510. 122. Gaffey MJ, Mills SE, Frierson HF Jr, et al. Medullary carcinoma of the breast: interobserver variability in histopathologic diagnosis. Mod Pathol 1995;8(1):3138. 123. Sorlie T, Perou CM, Tibshirani R, et al. Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications. Proc Natl Acad Sci U S A 2001; 98(19):1086910874. 124. Sorlie T, Tibshirani R, Parker J, et al. Repeated observation of breast tumor subtypes in independent gene expression data sets. Proc Natl Acad Sci U S A. 2003;100(14):84188423. 125. Nielsen TO, Hsu FD, Jensen K, et al. Immunohistochemical and clinical characterization of the basal-like subtype of invasive breast carcinoma. Clin Cancer Res 2004;10(16):53675374. 126. Page D, Sakamoto G. Inltrating carcinoma: major histological types. In: Page D, Anderson TJ, eds. Diagnostic Histopathology of the Breast. Edinburgh, NY: Churchill Livingstone; 1987:206210. 127. Fisher ER, Palekar AS, Redmond C, et al. Pathologic ndings from the National Surgical Adjuvant Breast Project (protocol no. 4). VI. Invasive papillary cancer. Am J Clin Pathol 1980;73(3):313322. 128. Nassar H. Carcinomas with micropapillary morphology: clinical signicance and current concepts. Adv Anat Pathol 2004;11(6):297303. 129. Chhieng C, Cranor M, Lesser ME, et al. Metaplastic carcinoma of the breast with osteocartilaginous heterologous elements. Am J Surg Pathol 1998;22(2):188194. 130. Ro JY, Silva EG, Gallager HS. Adenoid cystic carcinoma of the breast. Hum Pathol 1987;18(12):12761281. 131. Chang J, Hilsenbeck SG. Prognostic and Predictive Markers. 3rd ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2004. 132. Singletary SE, Allred C, Ashley P, et al. Revision of the American Joint Committee on Cancer staging system for breast cancer. J Clin Oncol 2002;20(17):36283636. 133. Carter C, Allen C, Henson DE. Relation of tumor size, lymph node status and survival of 24,740 breast cancer cases. Cancer 1989;63(1):181187. 134. Fisher B, Dignam J, Tan-Chiu E, et al. Prognosis and treatment of patients with breast tumors of one centimeter or less and negative axillary lymph nodes. J Natl Cancer Inst 2001;93(2):112120. 135. Adair F, Berg J, Joubert L, et al. Long-term followup of breast cancer patients: the 30-year report. Cancer 1974;33(4):11451150.

61

136. Elston CW, Ellis IO. Pathological prognostic factors in breast cancer. I. The value of histological grade in breast cancer: experience from a large study with long-term follow-up. Histopathology 1991;19(5):403410. 137. Frierson HF Jr, Wolber RA, Berean KW, et al. Interobserver reproducibility of the Nottingham modication of the Bloom and Richardson histologic grading scheme for inltrating ductal carcinoma. Am J Clin Pathol 1995;103(2):195198. 138. Hammond E, Hayes DF, Dowsett M, et al. American Society of Clinical Oncology /College of American Pathologists guideline recommendations for immunohistochemical testing of estrogen and progesterone receptors in breast cancer. Arch Pathol Lab Med. Early online release 2010. 139. Tamoxifen for early breast cancer: an overview of the randomised trials. Early Breast Cancer Trialists Collaborative Group. Lancet 1998;351(9114):14511467. 140. Ellis MJ, Coop A, Singh B, et al. Letrozole is more effective neoadjuvant endocrine therapy than tamoxifen for ErbB-1- and/or ErbB-2-positive, estrogen receptor-positive primary breast cancer: evidence from a phase III randomized trial. J Clin Oncol 2001;19(18): 38083816. 141. Paik S, Bryant J, Tan-Chiu E, et al. Real-world performance of HER2 testingNational Surgical Adjuvant Breast and Bowel Project experience. J Natl Cancer Inst. 2002;94(11): 852854. 142. Wolff AC, Hammond E, Schwartz JN, et al. American Society of Clinical Oncology/ College of American Pathologists guideline recommendations for human epidermal growth factor receptor 2 testing in breast cancer. J Clin Oncol 2007;25(1):118145. 143. Gusterson BA, Gelber RD, Goldhirsch A, et al. Prognostic importance of c-erbB-2 expression in breast cancer. International (Ludwig) Breast Cancer Study Group. J Clin Oncol 1992;10(7):10491056. 144. Clayton F. Pathologic correlates of survival in 378 lymph node-negative inltrating ductal breast carcinomas. Mitotic count is the best single predictor. Cancer 1991;68(6): 13091317. 145. van Diest PJ, Baak JP, Matze-Cok P, et al. Reproducibility of mitosis counting in 2,469 breast cancer specimens: results from the Multicenter Morphometric Mammary Carcinoma Project. Hum Pathol 1992;23(6):603607. 146. Dettmar P, Harbeck N, Thomssen C, et al. Prognostic impact of proliferation-associated factors MIB1 (Ki-67) and S-phase in node-negative breast cancer. Br J Cancer 1997; 75(10):15251533. 147. OReilly SM, Camplejohn RS, Barnes DM, et al. Node-negative breast cancer: prognostic subgroups dened by tumor size and ow cytometry. J Clin Oncol 1990;8(12):20402046. 148. de Mascarel I, Bonichon F, Durand M, et al. Obvious peritumoral emboli: an elusive prognostic factor reappraised. Multivariate analysis of 1320 node-negative breast cancers. Eur J Cancer 1998;34(1):5865. 149. Davis BW, Gelber R, Goldhirsch A, et al. Prognostic signicance of peritumoral vessel invasion in clinical trials of adjuvant therapy for breast cancer with axillary lymph node metastasis. Hum Pathol 1985;16(12):12121218. 150. Perou CM, Sorlie T, Eisen MB, et al. Molecular portraits of human breast tumours. Nature 2000;406(6797):747752. 151. Sotiriou C, Neo SY, McShane LM, et al. Breast cancer classication and prognosis based on gene expression profiles from a population-based study. Proc Natl Acad Sci U S A 2003;100(18):1039310398. 152. Rouzier R, Perou CM, Symmans WF, et al. Breast cancer molecular subtypes respond differently to preoperative chemotherapy. Clin Cancer Res 2005;11(16):56785685. 153. OShaughnessy J, O Osborne, Pippen J, et al. Efcacy of BSI-201, a poly (ADP-ribose) polymerase-1 (PARP1) inhibitor, in combination with gemcitabine/carboplatin (G/C) in patients with metastatic triple-negative breast cancer (TNBC): Results of a randomized phase II trial [Abstract P3]. J Clin Oncol 2009;27:18S. 154. Paik S, Shak S, Tang G, et al. A multigene assay to predict recurrence of tamoxifentreated, node-negative breast cancer. N Engl J Med 2004;351(27):28172826. 155. Paik S, Tang G, Shak S, et al. Gene expression and benet of chemotherapy in women with node-negative, estrogen receptor-positive breast cancer. J Clin Oncol 2006;24(23): 37263734. 156. Albain K, Barlow W, Shak S, et al. Prognostic and predictive value of the 21-gene recurrence score assay in postmenopausal, node-positive, ER positive breast cancer. Breast Cancer Res Treat 2008;84(S8814). 157. Glas AM, Floore A, Delahaye LJ, et al. Converting a breast cancer microarray signature into a high-throughput diagnostic test. BMC Genomics 2006;7:278. 158. Buyse M, Loi S, vant Veer L, et al. Validation and clinical utility of a 70-gene prognostic signature for women with node-negative breast cancer. J Natl Cancer Inst 2006;98(17): 11831192. 159. Bogaerts J, Cardoso F, Buyse M, et al. Gene signature evaluation as a prognostic tool: challenges in the design of the MINDACT trial. Nat Clin Pract Oncol 2006;3(10):540551.

CHAPTER

6
There are a number of criteria that increase a womans risk for breast cancer. Generally these can be divided into three categories: histologic lesions, demographic factors, and genetic mutations (see Chapter 1). In this chapter we focus on dening the risk associated with benign breast histologic ndings and the clinical management of high-risk patients as dened by histologic or demographic criteria.

Therese S. Cermak Jennifer Eng-Wong

Dening and Managing the High-risk Patient


mild or usual if there is no bridging or distention of the intraductal space, and these changes are considered nonproliferative (3). Fibroadenoma is a benign proliferation of the hormonally responsive intralobular stroma. However, the proliferation in these benign lesions is not due to loss of normal function or clonal proliferation of the breast epithelium. The literature is challenging to summarize, given that each investigator can include a variety of diagnoses in the overarching category of nonproliferative lesions. On the whole these lesions are associated with minimal to no increased risk of developing breast carcinoma (1419). An early series from Dupont and Page with 17 years follow-up reports a relative risk (RR) of 0.9 (95% condence interval [CI] 0.6 to 1.3) for developing breast cancer compared to a healthy survey cohort (17). In 2005, Hartmann et al. published long-term follow-up results from women who received a diagnosis of benign breast disease at the Mayo Clinic between 1967 and 1991 (8). This included 9,087 cases followed for a median of 15 years. Women with nonproliferative lesions had a relative risk of 1.3 (95% CI 1.2 to 1.4) for developing breast cancer compared to the population at large (Table 6.1).

DEFINING RISK BASED ON HISTOLOGIC LESIONS


Although nearly 95% of women with abnormalities on screening mammography do not have breast cancer, evaluation of their tissue has advanced scientic understanding of the spectrum of changes that occur in the breast and the risk associated with these changes (1). The relationship between breast lesions and cancer risk is complex, but certain principles have been established that can inform clinical care (2). Pathologic diagnosis from needle core biopsy samples has become the primary determinant of further intervention, and pathologists have made attempts to classify the spectrum of histologic ndings into reproducible and relevant categories (35). Noninvasive changes in the glandular epithelium of the breast can be divided into four categories: nonproliferative, proliferative without atypia, proliferative with atypia, and carcinoma in situ. The validity of these categories of breast lesions is supported by the nding that there is an increased risk for developing breast cancer associated with proliferative changes. This risk is more than doubled when the proliferative changes include atypia and may persist for 10 years or more after biopsy (610).

PROLIFERATIVE LESIONS
Proliferative breast lesions provide the rst morphologic evidence of genetic alteration, such as increased estrogen receptor expression, but they lack the full spectrum of cellular changes found in malignancy (20,21). These lesions may be detected as irregular densities or calcications on mammography (22). The type and extent of proliferation on a biopsy specimen are major factors used in assessing risk for developing breast cancer. This category of lesions includes moderate to orid usual ductal hyperplasia, columnar cell hyperplasia, small duct papillomas, sclerosing adenosis, and complex sclerosing lesions (radial scar) (3,8). Moderate to orid hyperplasia is considered proliferative and is defined as more than three or four cell layers, with bridging, distention, or lling of the ducts and lobules (23,24). Papillomas can be multiple, and consist of a proliferation of ductal epithelium around a brovascular core. Sclerosing adenosis and complex sclerosing lesions consist of various combinations of increased acini entrapped in dense stroma. The term scar in the case of radial scar refers to the appearance of the complex sclerosing lesion and does not indicate prior trauma or surgery. These proliferative lesions are often found in various combinations within the same biopsy specimen, and all of the proliferative lesions without atypia are associated with a similar relative risk (RR range 1.3 to 1.9) for developing breast cancer (3,6,810,17). For example in the Nurses Health Study (1976 to 1996) and the Nurses Health Study II (1989 to 1995) Collins et al. identied more than 1,000 cases of proliferative breast disease without atypia. These included 200 cases that

NONPROLIFERATIVE LESIONS
Nonproliferative benign lesions are considered to be in the spectrum of normal and confer no increased risk of developing breast cancer. The nonproliferative category includes cysts, apocrine metaplasia, columnar cell change without atypia, fibroadenomas, nonsclerosing adenosis, and mild (usual) hyperplasia. These lesions may form palpable masses, may change in response to hormones, and can be associated with mammographic calcifications (1113). Apocrine metaplasia and columnar cell change without atypia are benign alterations in the cuboidal epithelium lining the ducts and lobules. However, the designation of broadenomas, nonsclerosing adenosis, and mild hyperplasia as nonproliferative is not entirely accurate. Mild (usual) hyperplasia and nonsclerosing adenosis are physiologic proliferations of glandular epithelium and acini, respectively. The denition of hyperplasia for the glandular epithelium of the breast is the presence of more than the normal two cell layers, myoepithelial and epithelial, above the basement membrane. Hyperplasia is further characterized as

62

Chapter 6 Dening and Managing the High-risk Patient

63

TABLE 6.1
Author, Year Published
Dupont 1985 (17)b,c Page 1985 (3)b Dupont 1993 (10)d Marshall 1997 (6)d,e Hartmann 2005 (8)b,c Collins 2007 (9)d,e
a

Risk of Breast Cancer Based on Morphology of Benign Breast Diseasea


Median Follow-up (yr)
17 17 10 10 15 9

N
3,303 268 95 cases, 227 controls 51 cases, 191 controls 9,087 395 cases, 1,610 controls

Nonproliferative
0.9 (0.61.3) 1 1 (ref) 1 (ref) 1.3 (1.21.4) 1 (ref)

Proliferative Without Atypia


1.9 (1.22.9) NR 1.3 (0.72.2) 1.7 (1.22.6) 1.9 (1.72.1) 1.5 (1.22.0)

Atypical Hyperplasia
4.4 (3.16.3) 5.3 (3.18.8) 4.3 (1.711) 3.4 (2.05.9) 4.2 (3.35.4) 4.1 (2.95.8)

NR, not reported; ref, reference group. All authors used the Page diagnostic criteria for dening breast lesions (95% condence interval). b Retrospective cohort study. c Compared to study-dened healthy population. d Nested casecontrol study. e Risk includes invasive and noninvasive breast cancer.

later developed breast cancer. The relative risk for developing breast cancer associated with proliferative changes without atypia is 1.5 (95% CI 1.2 to 2.0) (9). If cancer occurs later, it occurs ipsilateral to the benign breast disease 50.3% of the time. This supports the current concept of these lesions as markers for increased risk, as opposed to being precursor lesions.

ATYPICAL LESIONS
Atypical lesions have proliferating, monomorphic cells and exhibit additional loss of normal cell function (25). These lesions are detected in approximately 10% of biopsies for microcalcifications or a palpable mass, and include atypical lobular hyperplasia (ALH), lobular carcinoma in situ (LCIS), atypical ductal hyperplasia (ADH), atypical columnar cell change, and at epithelial atypia (22,26). Of note, the term lobular neoplasia (LN) encompasses the spectrum of atypical proliferations originating in the lobule, from ALH to LCIS, which can be difficult to distinguish (27). The term flat epithelial atypia was introduced by the WHO Working Group on the Pathology and Genetics of Tumours of the Breast in 2003 in an attempt to consolidate diagnostic terms for epithelial atypia that lacks the architectural complexity of ADH or the features of columnar cell change (25,28). Atypical hyperplasias (AHs) are lesions that fall short of the quantitative and/or qualitative histologic criteria for designation as carcinoma in situ and often present a diagnostic dilemma, with interobserver agreement reaching only 45% to 53% (4,24,2931). Atypical lesions in general are associated with a relative risk for developing breast cancer of 4.2 (range reported 3.3 to 5.4) (79). While ALH and ADH are generally considered equivalent in regard to risk of future breast cancer, recent evidence suggests that the risk associated with ALH is higher than the risk with ADH. In one report the relative risk for women with ALH is 5.8 versus 3.1 for ADH, and if the woman is premenopausal at the time of biopsy, the risk associated with ALH is 7.3, while with ADH it is 2.7 (9). ALH and ADH are associated with future ipsilateral invasive breast cancer slightly more than half of the time (61.3% and 55.9%,

respectively) and still should be considered background markers of general increased risk (9,25). Concerns over diagnostic accuracy have been addressed with dissemination of clearer guidelines; however, discordance in diagnosing these lesions persists (4,24,31,32). In a recent assessment of accuracy, pathologists from 22 institutions reviewed 2,004 needle core breast biopsies locally from samples obtained as part of a multicenter trial. The biopsies then underwent central review, and the local and central diagnoses were compared. The investigators found high interobserver agreement (99%) for benign lesions and invasive cancers (97%). The diagnosis of ductal carcinoma in situ (DCIS) was concordant in 83% of cases. However, lower levels of agreement were seen for atypical ductal hyperplasia (ADH) (63%) and lobular neoplasia (inclusive of atypical lobular hyperplasia and lobular carcinoma in situ) (53%) (31). The lack of uniformity in the pathologic diagnosis of atypia reects the complexity of these lesions and our imperfect understanding of them. The limitations of morphology inspire attempts to identify molecular markers and proles to distinguish these lesions for diagnostic purposes as well as ascertain whether AH are obligate precursor lesions or reective of a background environment. Estrogen is a well-recognized breast cancer growth factor. Higher-than-expected estrogenreceptor (ER) levels are seen in AH (60%) compared with normal breast epithelium (7%), and this nding is in keeping with the observation that the majority of DCIS and invasive carcinomas are ER-positive, suggesting a precursor relationship (33). A number of investigators have evaluated premalignant lesions for allelic imbalance or loss of heterozygosity (LOH). In one report on 17 cancer-containing specimens where ADH and cancer coexist, LOH was evaluated by polymerase chain reaction on microdissected samples. The ADH and cancer exhibited concordance, that is, LOH in the same allele, in 82% (9 of 11) of evaluable cases (34). However in another series of seven patients who had atypical hyperplastic lesions from 2 to 16 years preceding the diagnosis of invasive cancer, no cases showed concordance, suggesting that the path between AH and cancer is not a direct route (35). Clearly, further study is needed in this area. As scientic knowledge expands, the picture of atypia will become more clearly focused.

64

Section I Oncology and Oncoplastic Surgery

EFFECT OF OTHER FACTORS ON BENIGN BREAST DISEASE AND BREAST CANCER RISK
The effect of family history and menopausal status on benign breast disease and risk of breast cancer has been examined in a number of reports. In the retrospective cohort analyses by Page and Dupont, if a woman had a rst-degree relative with breast cancer and proliferative disease with or without atypia, the risk of future cancer at least doubled, for example, from 3.2 to 9.7 for women with atypia (3,17). In the nested case control trial from the Breast Cancer Detection and Demonstration Project (BCDDP) a family history of breast cancer doubled the risk associated with proliferative disease without atypia (1.3 to 2.6) and with atypia (4.3 to 22) (10). It is important to note that the number of participants on which these risk estimates are based is small and the methodology for obtaining family history is not reported. In the largest and most recent series, Hartmann more carefully dened family history of breast cancer and found no interaction between benign breast disease and family history (8). In summary, there are conicting data on the effect of a family history of breast cancer in women with proliferative breast disease, although a more recent analysis does not support an interaction. In regard to age and risk, both the initial and subsequent analyses of the Nurses Health Study found that premenopausal status increases risk of breast cancer for women with atypical lobular hyperplasia but not ductal hyperplasia or proliferative lesions without atypia (6,9). In the Mayo cohort, women who were less than 45 years old at the time atypia was diagnosed had more than twice the risk of developing breast cancer compared to women who were over 55 years of age (8). In the BCDDP analysis Dupont et al. report similar observations by menopause status (10). ALH and ADH were not reviewed separately in the Mayo or BCDDP analysis. Younger age at diagnosis of atypical hyperplasia more consistently shows higher risk for developing future breast cancer (Table 6.2). The specic risk associated with ALH versus ADH needs clarication.

SURGICAL MANAGEMENT OF HIGH-RISK PATHOLOGIC LESIONS


Nonproliferative lesions diagnosed on core biopsy typically require no further surgical intervention. However, there is lack of consensus on management of ADH and lobular neoplasia, and the approach varies by institution. The incidence of associated DCIS or invasive breast cancer (IBC) following diagnosis by core biopsy ranges widely in published series from 0% to 50%, although larger series have more consistently reported an incidence of carcinoma ranging from 10% to 20% (26,3639). These incidence rates are based on retrospective reviews, which have built-in limitations. The largest series from 32,420 women who had biopsies for imaging abnormalities found lobular neoplasia in 0.9% (N 278). Of these, 59% (N 164) went on to excisional biopsy, where cancer was found in 23% (N 38). The rates of cancer were the same for ALH and LCIS (39). In another series of 2,053 core breast biopsies, 49 (46%) women had ADH, 45 (42%) women had LN, and 12 (12%) women had both ADH and LN. In the ADH cases that went on to have excisional biopsy, 22% (9 of 41) were associated with DCIS or IBC; 14% of LN cases that went on to have excisional biopsy were associated with DCIS or IBC (3 of 21 cases: 1 DCIS, 2 IBC) (38). There is no information on criteria for when excisional biopsy was pursued. No radiology findings or clinical factors have been identied to further dene which women with LN are at increased risk for concurrent DCIS or IBC. In light of current ndings, excisional biopsy following a core biopsy diagnosis of ADH and LN is prudent.

BREAST CANCER RISK MODELS


In addition to histologic criteria to identify women at increased risk for breast cancer, demographic information can also help to determine risk and inform clinical decisions. The Breast Cancer Risk Assessment Tool, commonly referred to as the Gail

TABLE 6.2

Modiers of Risk of Developing Breast Cancer Based on Benign Breast Disease Diagnosis (9)
Additional Modiers of Risk Years Since Diagnosis Relative Risk 10
1 (ref)

Menopausal Status Pre


1 (ref)

10
1 (ref)

Post
1 (ref)

Nonproliferative changes Cysts, apocrine metaplasia, broadenoma, adenosis, columnar change, and mild hyperplasia Proliferative changes without atypia Moderate to orid hyperplasia, sclerosing adenosis, small duct papilloma(s) Atypical proliferative changes Atypical ductal hyperplasia Atypical lobular hyperplasia ref, reference group.

1 (ref)

1.5

1.4

1.6

1.4

1.9

3.1 5.5

2.4 5.6

4.8 5.8

2.7 7.3

4.0 3.4

Chapter 6 Dening and Managing the High-risk Patient

65

model, is derived from the BCDDP data that predicts a womans chance of developing breast cancer using a number of risk factors: age, age of menarche, age at rst live birth, number of rst-degree relatives with breast cancer, number of breast biopsies, presence of atypical hyperplasia, and race (40). The Breast Cancer Risk Assessment Tool is an open-access, Webbased tool hosted on the National Cancer Institute Web site (http:/ /www.cancer.gov/bcrisktool). The Gail model is only appropriate for women over age 35 years without a personal history of in situ or invasive breast cancer. An additional limitation of the Gail model is a partial assessment of family history of breast and other cancers. Thus someone with a strong family history of breast and/or ovarian cancer should be assessed for risk by other means. The Gail model has been validated in a number of populations followed with annual screening mammograms (41,42) and correlates well with observed outcomes. The ratio of expected to observed cases of breast cancer ranges from 0.84 to 1.03 and is informative for predicting the risk of developing breast cancer in populations undergoing screening mammography. When using the Gail model in the clinical setting it is important to be aware of its limitations. At the individual level of risk prediction the Gail model has poor discriminatory accuracy, with attributable risk of 0.58, that is, little better than chance at determining risk (42). Moreover, the clinical trial data on which the Gail model was originally developed included solely White women, so that the utility of the model in other races was not known. Recently the model has been updated by adding data from the Womens Contraceptive and Reproductive Experiences study, which included 3,200 African American women (43). Inclusion of more African Americans resulted in higher risk estimates for Black women over age 45 years. In efforts to improve risk prediction at the individual level, mammographic density has also been added to the algorithm (44). In the model, mammographic density is dened as average percentage of dense area of the two breasts in the craniocaudal view. However, this version of the Gail model has not yet been independently validated. In regard to accurately predicting ER-positive versus ER-negative breast cancers, one study evaluated this in postmenopausal women only. In the Womens Health Initiative, the Gail model was a better predictor of ER-positive cancer (area under the curve [AUC] 0.60, 95% CI 0.58 to 0.62) than ER-negative cancer (AUC 0.50, 9%5 CI 0.45 to 0.54). Age and age at menopause were not associated with ER-negative cancer (45). Other risk models that have been developed to address individuals with a strong family history of breast and/or ovarian cancer. The Claus and Tyrer-Cuzick models predict the lifetime risk of developing breast cancer in women with a family history of breast and/or ovarian cancer (4648). The BRCAPRO and Couch models predict the risk of being a BRCA1/2 mutation carrier (49,50).

insulin-like growth factor pathway (52), body mass index (53), estradiol and sex hormonebinding globulin, and other factors (54). MD has recently been shown to be a useful surrogate biomarker in the International Breast Cancer Intervention Study (IBIS-I); patients with a 10% decline in MD on tamoxifen had a 52% reduction in breast cancer incidence (55). However, MD is typically not included on standard mammogram reports and remains a research tool.

BREAST CANCER PREVENTION AGENTS


SELECTIVE ESTROGEN RECEPTOR MODULATORS: TAMOXIFEN AND RALOXIFENE Currently there are two agents that are approved by the U.S. Food and Drug Administration for breast cancer risk reduction. Tamoxifen and raloxifene are both selective estrogen receptor modulators (SERMS) shown to reduce breast cancer incidence in randomized phase III trials. These agents competitively bind to the estrogen receptor and exhibit both estrogen agonist and antagonist activity. Tamoxifen was the first agent to be widely tested in the prevention setting. The paradigm shift from treatment of breast cancer to prevention of breast cancer was predicated on adjuvant treatment trials showing a reduction of contralateral breast cancer with tamoxifen use (56). Tamoxifen has been tested against placebo in four randomized phase III trials enrolling approximately 28,000 women and has been found to reduce breast cancer by 38% (95% CI 28 to 46) and estrogen receptorpositive breast cancers by 48% (95% CI 36, 58) (57). There was no decrease in estrogen receptornegative breast cancer. Denition of a high-risk woman varied by trial. Factors considered included family history, demographic risk factors, high-risk histologic lesions, and Gail model risk assessment (5861). Regardless of the denition, women who received tamoxifen had fewer cases of estrogen receptorpositive invasive and noninvasive breast cancer. The largest phase III trial, the National Surgical Adjuvant Breast and Bowel Project (NSABP) P-1 or Breast Cancer Prevention Trial, randomized 13,388 women. The study dened high risk as 60 years of age or older, or 35 to 59 years old with a Gail model risk of 1.66% over 5 years, or a history of LCIS. The investigators found that tamoxifen decreased the incidence of invasive breast cancer by 49% and that of noninvasive cancer by 50% (58). In addition, the protective effects of 5 years of tamoxifen therapy persist for up to another 5 years after nishing treatment (62). Based on the P-1 results, it is estimated that chemopreventive use of tamoxifen would lead to more than 700,000 fewer cases of breast cancer over 5 years in the United States (63). Women with a history of benign breast disease dened as a histologic diagnosis of adenosis, cyst, duct ectasia, brocystic disease, broadenoma, brosis, hyperplasia, or metaplasia enrolled on the P-1 trial were evaluated in a substudy. Participants on the tamoxifen arm had a reduction in subsequent proliferative, nonproliferative, and atypical benign breast disease by 28% and underwent 29% fewer biopsies at 69 months follow-up; women less than 50 years old experienced the greatest benet (64). Although a reduction in benign breast disease may have little impact on clinical outcomes, a reduction in the number of biopsies is certainly benecial to the patient and to control health care costs.

MAMMOGRAPHIC DENSITY
Mammographic density (MD) is a well-recognized risk factor for breast cancer and can be measured with quantitative techniques. The risk for developing breast cancer for women with denser breasts compared with women with less dense breasts ranges from 1.8 to 6.0, with most studies yielding an odds ratio of 4.0 or greater (51). MD is a dynamic value inuenced by the

66

Section I Oncology and Oncoplastic Surgery

TABLE 6.3

Events on Tamoxifen and Raloxifene in Women at Risk for Breast Cancer (74,75)
Tamoxifen Annual Event Rate/1000 Raloxifene Annual Event Rate/1000
5.02 2.23 1.38 1.23 1.33 11.69 2.51

Risk Ratio*
1.24 1.22 0.72 0.55 0.96 0.80 0.92

95% CI
1.05,1.47 0.95, 1.59 0.54, 0.95 0.36, 0.83 0.64, 1.43 0.72, 0.89 0.69, 1.22

Invasive breast cancer Non-invasive breast cancer Thrombo-embolic events Endometrial cancer Stroke Cataracts Osteoporotic fractures

4.04 1.83 1.93 2.25 1.39 14.58 2.73

*Risk ratio for women in raloxifene group compared to women in the tamoxifen group.

Tamoxifen has other benecial effects; it increases bone density in postmenopausal women and reduces osteoporosisrelated fractures (65). Tamoxifen reduces total cholesterol and low-density lipoprotein, although no difference in myocardial infarction has been seen in the prevention trials (66,67). In regard to potentially life-threatening adverse effects, tamoxifen has been shown to increase the risk of endometrial cancer (RR 2.4, 95% CI 1.5 to 4.0) and venous thromboembolic events (RR 1.9, 95% CI 1.4 to 2.6) (57). The magnitude of risk for these adverse events has also been shown to increase with age; however the effectiveness of tamoxifen in reducing breast cancer risk does not differ by age (57,58). Nonlife-threatening side effects include hot ashes, vaginal discharge, and cataracts (RR 1.14, 95% CI 1.01 to 1.29) (58). Prospective quality-of-life analyses showed no difference in depression (68,69), and weight gain did not differ between placebo and tamoxifen arms at 5 years (60). Adverse events diminish immediately on stopping tamoxifen. Despite these positive results, the uptake of tamoxifen as a prevention agent has been limited due to reluctance of both patients and physicians (70,71). The effectiveness of raloxifene was shown in the NSABP P2 trial or Study of Tamoxifen and Raloxifene (STAR) trial. The rationale for evaluation of raloxifene was to nd an agent with similar efcacy to tamoxifen but with a better side effect prole. Prior trials in women with osteoporosis showed that raloxifene reduced the incidence of breast cancer without increasing the risk of endometrial cancer (72). The Multiple Outcomes of Raloxifene trial randomized postmenopausal women with osteoporosis to placebo or raloxifene at either 60 mg daily or 120 mg daily for 4 years. Breast cancer incidence was evaluated as a secondary endpoint. Women who took raloxifene had a 72% decrease in breast cancer incidence (RR 0.38, 95% CI 0.24 to 0.58) (84% decrease in ER-positive breast cancer) compared to those on placebo. Four thousand of these women continued to receive raloxifene or placebo for an additional 4 years in the Continuing Outcomes Relevant to Evista trial. Over the 8 years of treatment raloxifene reduced invasive breast cancer by 66% compared to placebo, with a 76% decrease in estrogen receptorpositive cancers and no difference in the number of estrogen receptornegative cancers (73). The P-2 trial randomized 19,747 postmenopausal women at increased risk of breast cancer to tamoxifen or raloxifene for 5 years. Initially the trial demonstrated that tamoxifen and raloxifene were equivalent in reducing breast cancer incidence (74), however with 81 month median follow up tamox-

ifen appears to be more effective than raloxifene in preventing invasive breast cancer (Table 6-3) (75). The rate of invasive breast cancer on raloxifene was 24% higher than on tamoxifen (RR1.24, 95% CI 1.05, 1.47). Extrapolating from this data the authors estimate that raloxifene decreases the incidence of invasive breast cancer by 38% compared with placebo, while tamoxifen does so by 50% compared with placebo. There was no difference between arms in risk of non-invasive cancers (RR 1.22, 95% CI 0.95, 1.59) (74). There is no evidence to date that decreasing breast cancer incidence results in lower breast cancer mortality rate. Rates of stroke and ischemic cardiac events did not differ between the two arms (74), although thromboembolic events were less common on the raloxifene arm (RR 0.75 95% CI 0.60, 0.93) (75). Additionally endometrial cancer and cataract incidence were signicantly less common on the raloxifene arm. Non life-threatening side effects of raloxifene are similar to tamoxifen and include hot ashes and leg cramps. Tamoxifen and/or raloxifene should be discussed with women at increased risk of breast cancer as a risk reduction strategy (Table 6-4). BREAST CANCER PREVENTION AGENTS IN BRCA MUTATION CARRIERS The reports on prevention agents in BRCA1/2 mutation carriers are few in number and small in scale. In the P-1 trial a subgroup analysis of BRCA1/2 mutation carriers was conducted. Only 19 (6.6%) of the 288 breast cancers occurred in women with BRCA1/2 mutations, and the results are inconclusive due to the small sample size (76). In a casecontrol analysis

TABLE 6.4

Clinical Considerations for Chemoprevention


Menopause Status Agent
Pre Post Pre Post Pre Post Tamoxifen Raloxifene or tamoxifen Tamoxifen Raloxifene or tamoxifen Tamoxifen Raloxifene or tamoxifen

Risk Factor
Gail model 1.66% over 5 yr Lobular carcinoma in situ/atypical hyperplasia Strong family historya
a

Limited data in BRCA1/BRCA2 mutation carriers.

Chapter 6 Dening and Managing the High-risk Patient

67

(N 593) the effect of tamoxifen on contralateral breast cancer in BRCA1/2 mutation carriers showed that tamoxifen reduced the risk of contralateral breast cancer by 62% in BRCA1 mutation carriers and by 37% in BRCA2 mutation carriers (77). BRCA1 mutation carriers are more likely to develop hormone receptornegative breast cancer, while BRCA2 mutation carriers are more likely to develop hormone receptor positive cancer. Thus SERMs would be expected to yield greater benet in BRCA2 mutation carriers, although this has not been clinically validated (78). Surgical prophylaxis is effective in these high-risk patients (7982). AROMATASE INHIBITORS The aromatase inhibitors (AIs) are oral agents currently used as rst-line treatment for hormone receptorpositive invasive breast cancer in the adjuvant and metastatic treatment settings. These agents work by binding the aromatase enzyme and preventing estrogen production. As with tamoxifen, the rationale for evaluating AIs in the prevention setting comes from treatment trials. Results of the Anastrozole, Tamoxifen Alone or in Combination (ATAC) trial, which compared anastrozole, tamoxifen, and the combination of these two agents in the adjuvant setting, found a risk reduction of 58% in contralateral breast cancers with anastrozole-alone compared with singleagent tamoxifen (82). Similar results in reductions in contralateral breast cancer were seen with the other third-generation aromatase inhibitors exemestane and letrozole when used after tamoxifen in the adjuvant treatment setting (84,85). Since these agents decrease the incidence of new breast cancers more than tamoxifen and are well tolerated, they are under active investigation for breast cancer prevention in multiple randomized phase III trials. Table 6.5 lists the randomized phase III trial on AIs in the prevention and DCIS settings from which earliest results are expected in 2011 (86). Like SERMs, AIs are expected to reduce hormone receptorpositive breast cancer. Known side effects from the treatment setting include arthralgias, hot flashes, decrease in bone mineral density, and increased fracture risk. There is no identied increased risk of thromboembolic events or other cancers, which may make them more acceptable. The AI prevention trials include a num-

ber of secondary endpoints (bone density, quality of life, endometrial effects), which will provide further information on toxicity. Of note, these agents are only being evaluated in postmenopausal women, since premenopausal women can overcome the inhibitory effects of AIs. Thus tamoxifen is the only current and foreseeable choice for high-risk premenopausal women.

SURGICAL RISK REDUCTION


Surgical risk reduction is usually considered only in patients with a known BRCA1/2 mutation or strong family history. The efcacy of prophylactic mastectomies to reduce breast cancer is highly effective, approximately 90%. Oophorectomy if performed before age 50 years also reduces the risk of breast cancer by 50% (87,88). Oophorectomy should also be considered for reduction of ovarian cancer risk, although it is important to recognize that patients who have had an oophorectomy still have a risk of developing primary peritoneal cancer. Furthermore, these risk reductions are based on retrospective reviews, and no randomized trials have assessed this issue.

PREVENTION RESEARCH DIRECTIONS


ASSESSING BREAST TISSUE In an attempt to evaluate the breast without performing a biopsy a number of minimally invasive techniques have been evaluated. Ductal lavage is a technique to obtain ductal epithelial cells using breast duct endoscopy with saline wash. Nipple aspirate uid can be obtained by warming of the breast followed by suction of the nipple, and random periareolar ne needle aspiration (RPFNA) uses a 21-gauge needle to obtain cells circumferentially from around the nipple. These techniques yield cells for evaluation in the absence of stroma, and many have been evaluated in the research setting. Initial reports were promising on yield (89); however, subsequent studies of ductal lavage and nipple aspirate uid have shown them to be unreliable in regard to cellular yield and cytologic

TABLE 6.5

Ongoing Breast Cancer Prevention Trials with Aromatase Inhibitors


Aromatase Inhibitor
Anastrozole Anastrozole Exemestane Anastrozole Exemestane

Study
NSABP B-35 (104) IBIS-II (DCIS) (105) CAN-NCIC-MAP3 (106) IBIS-II (107) ApreS (Italy) (108)

Comparator
Tamoxifen Tamoxifen Placebo Placebo Placebo

Population
HR DCIS HR DCIS High risk High risk BRCA1/2 mutation carriers

N
3,000 4,000 4,560 6,000 400

Year Opened
2003 2003 2004 2003 2004

ApreS, Exemestane Prevention Study; CAN-NCIC-MAP3, Bone Mineral Density in Postmenopausal Women at Increased Risk of Developing Breast Cancer and Who Are Receiving Exemestane on Clinical Trial; DCIS, ductal carcinoma in situ; HR, hormone receptorpositive; IBIS-II, Second International Breast Cancer Intervention Study; NSABP, National Surgical Adjuvant Breast and Bowel Project.

68

Section I Oncology and Oncoplastic Surgery

reproducibility in women at high risk for breast cancer (90,91). Patil et al. found that even with cannulation of the same duct they were not able to reproduce cytological results (91). In addition, the nding of atypical cells has not been associated with magnetic resonance imaging changes or histologic changes in women who have undergone mastectomy or future development of cancer (92,93). RPFNA may be a more reliable method to obtain adequate number of cells compared with ductal lavage (94). One study of RPFNA in high-risk women (dened as a family history of breast cancer, prior history of breast cancer, or high-risk pathologic lesion) found that hyperplasia with atypia and an elevated Gail risk score predicted a 15% risk of subsequent breast cancer at 3 years (95). To date these techniques have been limited to the research setting and have not met benchmarks for incorporation into routine clinical management of high-risk patients. POTENTIAL BIOMARKERS OF RISK REDUCTION Other areas under investigation include the relationship of involution, or regression of lobules, and breast cancer risk. Changes in the lobules associated with aging include a reduction in the number and size of acini, replacement of intralobular stroma with dense collagen, and replacement of interlobular stroma by adipose tissue. The hypothesis is that a reduction in the number of acini may decrease the risk of developing breast cancer. In 2006, Milanese et al. did indeed find an inverse relationship between the degree of lobular involution and risk of breast cancer in women with benign breast disease (96). More recently, Vierkant et al. found that lobular involution appears to be a homogeneous process, the measure of which may be useful in assessing breast cancer risk (97). To date, however, there are no standard morphologic criteria for evaluating lobular involution. PROMISING PREVENTION INTERVENTIONS There are a number of other agents of interest, and most are under early investigation. The retinoids show promise as possible prevention agents, but their efcacy is as yet unproven. The most compelling evidence is from a phase III adjuvant treatment trial, in which women were randomized to observation or fenretinide for 5 years following local treatment for their breast cancer. An unplanned subgroup analysis showed that premenopausal women on fenretinide were less likely to have a second breast cancer. This nding persisted with 15-year follow-up of 60% of the women originally enrolled in the trial (98,99). Unfortunately, no data on hormone receptor status of the second cancers is available. Other agents of interest include vitamin D, statins, COX-2 inhibitors, insulin-modulating agents, and others. Lifestyle interventions are also of increasing relevance since there is mounting epidemiologic data that maintaining a healthy weight, engaging in regular exercise, and limiting alcohol intake are associated with reductions in breast cancer incidence (100103). In addition, the role of hormone replacement therapy in addition to low-dose tamoxifen for breast cancer risk reduction is under evaluation in a phase III trial (104).

atypia convey a higher risk of breast cancer, which persists up to 10 years following diagnosis. In addition to histologic lesions, demographic factors can be used to determine risk. Effective risk reduction agentstamoxifen for premenopausal and postmenopausal women and raloxifene for postmenopausal womenreduce the incidence of hormone receptorpositive breast cancer by nearly 50%. The aromatase inhibitors are under study for breast cancer prevention. New models and agents are needed to predict and prevent hormone receptor negative breast cancer.

EDITORIAL COMMENTS The mention of breast cancer evokes an emotional response. It is the most common malignancy in women and involves an organ that is the symbol of femininity. The majority of people have been touched by breast cancer in some way through family members or friends. Therefore its incidence and risk factors are of intense interest. Risk for breast cancer seems to be multifactorial and the epidemiologic study is difcult since the factors increasing risk may have been exerted on the developing breast during puberty while the actual disease develops many decades later. The risk for breast cancer is a continuum and one of the challenges of dealing with patients is counseling them about where they fall on that continuum. There is a range from a 13% lifetime risk of developing breast cancer in the average risk population to as high as an 85% risk in a gene mutation carrier. Histologic features, breast density, family history, history of radiation, especially at a young age, hormonal and reproductive factors and gene mutation status must all be factored into a risk assessment. We do not yet have a reliable method of predicting which individual in any risk category will develop the disease. Surveillance is challenging, and although fairly reliable, it is not foolproof. There are unfortunately many examples of later stage disease diagnosed in women who have undergone intense surveillance. Improvement in both individual risk assessment and surveillance would have a favorable outcome on patient outcomes. Most of the risk factors associated with an increased incidence of breast cancer are not under the patients control and simply identifying the patient at increased risk without offering risk-reducing strategies only adds to the patients anxiety about developing breast cancer. The ideal situation would be to identify those patients at increased risk and halt the progression of disease before malignant transformation occurs. Currently tamoxifen is the only approved chemopreventive agent for breast cancer for premenopausal women. Raloxifene is now approved for risk reduction in post-menopausal women. It is expected, based on ongoing clinical trials, that aromatase inhibitors will also be benecial for chemoprevention in post-menopausal women. As Dr. Cermak points out, however, the acceptance of these agents for chemoprevention is low. Many patients initiate the discussion about bilateral prophylactic mastectomy and ultimately elect to have surgery, especially if they have seen a loved one die of breast cancer. It seems a drastic measure, but

SUMMARY
Proliferative breast lesions are associated with a modest increased risk of breast cancer. Proliferative breast lesions with

Chapter 6 Dening and Managing the High-risk Patient

69

for the patient who has been counseled about the continued small but real risk of developing breast cancer, has been given time to make her own decision and is fully informed about her reconstruction options, acceptance and satisfaction is high. S.C.W.

REFERENCES
1. Elmore JG, Armstrong K, Lehman CD, et al. Screening for breast cancer. JAMA 2005;293: 12451256. 2. Page DL. Breast lesions, pathology and cancer risk. Breast J 2004;10(suppl 1):S3S4. 3. Page DL, Dupont WD, Rogers LW, et al. Atypical hyperplastic lesions of the female breast. A long-term follow-up study. Cancer 1985;55:26982708. 4. Schnitt SJ, Connolly JL, Tavassoli FA, et al. Interobserver reproducibility in the diagnosis of ductal proliferative breast lesions using standardized criteria. Am J Surg Pathol 1992;16: 11331143. 5. Masood S. Cytomorphology of brocystic change, high-risk proliferative breast disease, and premalignant breast lesions. Clin Lab Med 2005;25:713731. 6. Marshall LM, Hunter DJ, Connolly JL, et al. Risk of breast cancer associated with atypical hyperplasia of lobular and ductal types. Cancer Epidemiol Biomarkers Prev 1997;6: 297301. 7. Schnitt SJ. Benign breast disease and breast cancer risk: morphology and beyond. Am J Surg Pathol 2003;27:836841. 8. Hartmann LC, Sellers TA, Frost MH, et al. Benign breast disease and the risk of breast cancer. N Engl J Med 2005;353:229237. 9. Collins LC, Baer HJ, Tamimi RM, et al. Magnitude and laterality of breast cancer risk according to histologic type of atypical hyperplasia: results from the Nurses Health Study. Cancer 2007;109:180187. 10. Dupont WD, Parl FF, Hartmann WH, et al. Breast cancer risk associated with proliferative breast disease and atypical hyperplasia. Cancer 1993;71:12581265. 11. Vogel PM, Georgiade NG, Fetter BF, et al. The correlation of histologic changes in the human breast with the menstrual cycle. Am J Pathol 1981;104:2334. 12. Longacre TA, Bartow SA. A correlative morphologic study of human breast and endometrium in the menstrual cycle. Am J Surg Pathol 1986;10:382393. 13. Kushwaha AC, OToole M, Sneige N, et al. Mammographic-pathologic correlation of apocrine metaplasia diagnosed using vacuum-assisted stereotactic core-needle biopsy: our 4-year experience. AJR Am J Roentgenol 2003;180:795798. 14. Farrow JH. Fibroadenoma of the breast. CA Cancer J Clin 1961;11:182190. 15. Murad TM, Greider MH, Scarpelli DG. The ultrastructure of human mammary broadenoma. Am J Pathol 1967;51:663679. 16. London SJ, Connolly JL, Schnitt SJ, et al. A prospective study of benign breast disease and the risk of breast cancer. JAMA 1992;267:941944. 17. Dupont WD, Page DL. Risk factors for breast cancer in women with proliferative breast disease. N Engl J Med 1985;312:146151. 18. Carter CL, Corle DK, Micozzi MS, et al. A prospective study of the development of breast cancer in 16,692 women with benign breast disease. Am J Epidemiol 1988;128: 467477. 19. Ashbeck EL, Rosenberg RD, Stauber PM, et al. Benign breast biopsy diagnosis and subsequent risk of breast cancer. Cancer Epidemiol Biomarkers Prev 2007;16:467472. 20. Allred DC, Mohsin SK, Fuqua SA. Histological and biological evolution of human premalignant breast disease. Endocr Relat Cancer 2001;8:4761. 21. Shoker BS, Jarvis C, Clarke RB, et al. Estrogen receptorpositive proliferating cells in the normal and precancerous breast. Am J Pathol 1999;155:18111815. 22. Rubin E, Visscher DW, Alexander RW, et al. Proliferative disease and atypia in biopsies performed for nonpalpable lesions detected mammographically. Cancer 1988;61: 20772082. 23. Kumar V, Abbas AK, Fausto N. The breast. In: Robbins and Cotran Pathologic Basis of Disease. 7th ed. Philadelphia, Saunders; 2004:11191154. 24. Page DL, Rogers LW. Combined histologic and cytologic criteria for the diagnosis of mammary atypical ductal hyperplasia. Hum Pathol 1992;23:10951097. 25. Tavassoli FAH, Rosai H, Holland J, et al. Intraductal proliferative lesions. In: Tavassoli FA, Devilee P. eds. World Health Organization Classication of Tumours. Pathology and Genetics of Tumours of the Breast and Female Genital Organs. Lyon, France: IARC Press; 2003:6373. 26. Liberman L, Cohen MA, Dershaw DD, et al. Atypical ductal hyperplasia diagnosed at stereotaxic core biopsy of breast lesions: an indication for surgical biopsy. AJR Am J Roentgenol 1995;164:11111113. 27. Haagensen CD, Lane N, Lattes R, et al. Lobular neoplasia (so-called lobular carcinoma in situ) of the breast. Cancer 1978;42:737769. 28. OMalley FP, Mohsin SK, Badve S, et al. Interobserver reproducibility in the diagnosis of at epithelial atypia of the breast. Mod Pathol 2006;19:172179. 29. Elston CW, Sloane JP, Amendoeira I, et al. Causes of inconsistency in diagnosing and classifying intraductal proliferations of the breast. European Commission Working Group on Breast Screening Pathology. Eur J Cancer 2000;36:17691772. 30. Palli D, Galli M, Bianchi S, et al. Reproducibility of histological diagnosis of breast lesions: results of a panel in Italy. Eur J Cancer 1996;32A:603607. 31. Collins LC, Connolly JL, Page DL, et al. Diagnostic agreement in the evaluation of imageguided breast core needle biopsies: results from a randomized clinical trial. Am J Surg Pathol 2004;28:126131.

32. Rosai J. Borderline epithelial lesions of the breast. Am J Surg Pathol 1991;15:209221. 33. Schmitt FC. Multistep progression from an oestrogen-dependent growth towards an autonomous growth in breast carcinogenesis. Eur J Cancer 1995;31A:20492052. 34. Larson PS, de las Morenas A, Cerda SR, et al. Quantitative analysis of allele imbalance supports atypical ductal hyperplasia lesions as direct breast cancer precursors. J Pathol 2006;209:307316. 35. Tsuda H, Takarabe T, Akashi-Tanaka S, et al. Pattern of chromosome 16q loss differs between an atypical proliferative lesion and an intraductal or invasive ductal carcinoma occurring subsequently in the same area of the breast. Mod Pathol 2001;14:382388. 36. Middleton LP, Grant S, Stephens T, et al. Lobular carcinoma in situ diagnosed by core needle biopsy: when should it be excised? Mod Pathol 2003;16:120129. 37. Renshaw AA, Cartagena N, Derhagopian RP, et al. Lobular neoplasia in breast core needle biopsy specimens is not associated with an increased risk of ductal carcinoma in situ or invasive carcinoma. Am J Clin Pathol 2002;117:797799. 38. Arpino G, Allred DC, Mohsin SK, et al. Lobular neoplasia on core-needle biopsy: clinical signicance. Cancer 2004;101:242250. 39. Brem RF, Lechner MC, Jackman RJ, et al. Lobular neoplasia at percutaneous breast biopsy: variables associated with carcinoma at surgical excision. AJR Am J Roentgenol 2008; 190:637641. 40. Gail MH, Brinton LA, Byar DP, et al. Projecting individualized probabilities of developing breast cancer for White females who are being examined annually. J Natl Cancer Inst 1989;81:18791886. 41. Costantino JP, Gail MH, Pee D, et al. Validation studies for models projecting the risk of invasive and total breast cancer incidence. J Natl Cancer Inst 1999;91:15411548. 42. Rockhill B, Spiegelman D, Byrne C, et al. Validation of the Gail et al. model of breast cancer risk prediction and implications for chemoprevention. J Natl Cancer Inst 2001;93: 358366. 43. Gail MH, Costantino JP, Pee D, et al. Projecting individualized absolute invasive breast cancer risk in African American women. J Natl Cancer Inst 2007;99:17821792. 44. Chen JB, Pee D, Ayyagari R, et al. Projecting absolute invasive breast cancer risk in White women with a model that includes mammographic density. J Natl Cancer Inst 2006;98: 12151226. 45. Chlebowski RT, Anderson GL, Lane DS, et al. Predicting risk of breast cancer in postmenopausal women by hormone receptor status. J Natl Cancer Inst 2007;99:1695 1705. 46. Claus EB, Risch N, Thompson WD. Autosomal dominant inheritance of early-onset breast cancer. Implications for risk prediction. Cancer 1994;73:643651. 47. Claus EB, Risch N, Thompson WD. The calculation of breast cancer risk for women with a rst degree family history of ovarian cancer. Breast Cancer Res Treat 1993;28:115120. 48. Tyrer J, Duffy SW, Cuzick J. A breast cancer prediction model incorporating familial and personal risk factors. Stat Med 2004;23:11111130. 49. Parmigiani G, Berry D, Aguilar O. Determining carrier probabilities for breast cancersusceptibility genes BRCA1 and BRCA2. Am J Hum Genet 1998;62:145158. 50. Couch FJ, DeShano ML, Blackwood MA, et al. BRCA1 mutations in women attending clinics that evaluate the risk of breast cancer. N Engl J Med 1997;336:14091415. 51. Boyd NF, Rommens JM, Vogt K, et al. Mammographic breast density as an intermediate phenotype for breast cancer. Lancet Oncol 2005;6:798808. 52. Byrne C, Colditz GA, Willett WC, et al. Plasma insulin-like growth factor (IGF), IGFbinding protein 3, and mammographic density. Cancer Res 2000;60:37443748. 53. Boyd NF, Lockwood GA, Byng JW, et al. The relationship of anthropometric measures to radiological features of the breast in premenopausal women. Br J Cancer 1998;78: 12331238. 54. Boyd NF, Stone J, Martin LJ, et al. The association of breast mitogens with mammographic densities. Br J Cancer 2002;87:876882. 55. Cuzick JW, Pinney J, Warren L, et al. Change in breast density as a biomarker of breast cancer risk reduction; results from IBIS-1, abstract 61. Cancer Res Suppl 2008;69:77s. 56. Tamoxifen for early breast cancer: an overview of the randomised trials. Early Breast Cancer Trialists Collaborative Group. Lancet 1998;351:14511467. 57. Cuzick J, Powles T, Veronesi U, et al. Overview of the main outcomes in breast-cancer prevention trials. Lancet 2003;361:296300. 58. Fisher B, Costantino JP, Wickerham DL, et al. Tamoxifen for prevention of breast cancer: report of the National Surgical Adjuvant Breast and Bowel Project P-1 study. J Natl Cancer Inst 1998;90:13711388. 59. Powles T, Eeles R, Ashley S, et al. Interim analysis of the incidence of breast cancer in the Royal Marsden Hospital tamoxifen randomised chemoprevention trial. Lancet 1998;352: 98101. 60. Cuzick J, Forbes J, Edwards R, et al. First results from the International Breast Cancer Intervention Study (IBIS-I): a randomised prevention trial. Lancet 2002;360:817824. 61. Veronesi U, Maisonneuve P, Costa A, et al. Prevention of breast cancer with tamoxifen: preliminary ndings from the Italian randomised trial among hysterectomised women. Italian Tamoxifen Prevention Study. Lancet 1998;352:9397. 62. Cuzick J, Forbes JF, Sestak I, et al. Long-term results of tamoxifen prophylaxis for breast cancer: 96-month follow-up of the randomized IBIS-I trial. J Natl Cancer Inst 2007; 99:272282. 63. Fisher B. National Surgical Adjuvant Breast and Bowel Project breast cancer prevention trial: a reective commentary. J Clin Oncol 1999;17:16321639. 64. Tan-Chiu E, Wang J, Costantino JP, et al. Effects of tamoxifen on benign breast disease in women at high risk for breast cancer. J Natl Cancer Inst 2003;95:302307. 65. Powles TJ, Hickish T, Kanis JA, et al. Effect of tamoxifen on bone mineral density measured by dual-energy x- ray absorptiometry in healthy premenopausal and postmenopausal women. J Clin Oncol 1996;14:7884. 66. Braithwaite RS, Chlebowski RT, Lau J, et al. Meta-analysis of vascular and neoplastic events associated with tamoxifen. J Gen Intern Med 2003;18:937947. 67. Love RR, Wiebe DA, Feyzi JM, et al. Effects of tamoxifen on cardiovascular risk factors in postmenopausal women after 5 years of treatment. J Natl Cancer Inst 1994;86: 15341539.

70

Section I Oncology and Oncoplastic Surgery


88. Rebbeck TR, Lynch HT, Neuhausen SL, et al. Prophylactic oophorectomy in carriers of BRCA1 or BRCA2 mutations. N Engl J Med 2002;346:16161622. 89. Dooley WC, Ljung BM, Veronesi U, et al. Ductal lavage for detection of cellular atypia in women at high risk for breast cancer. J Natl Cancer Inst 2001;93:16241632. 90. Visvanathan K, Santor D, Ali SZ, et al. The reliability of nipple aspirate and ductal lavage in women at increased risk for breast cancer: a potential tool for breast cancer risk assessment and biomarker evaluation . Cancer Epidemiol Biomarkers Prev 2007;16: 950955. 91. Patil DB, Lankes HA, Nayar R, et al. Reproducibility of ductal lavage cytology and cellularity over a six month interval in high risk women. Breast Cancer Res Treat 2008;112: 327333. 92. Alberg AJ, Visvanathan K, Helzlsouer KJ. Epidemiology, prevention, and early detection of breast cancer. Curr Opin Oncol 1998;10:492497. 93. Carruthers CD, Chapleskie LA, Flynn MB, et al. The use of ductal lavage as a screening tool in women at high risk for developing breast carcinoma. Am J Surg 2007;194: 463466. 94. Arun B, Valero V, Logan C, et al. Comparison of ductal lavage and random periareolar ne needle aspiration as tissue acquisition methods in early breast cancer prevention trials. Clin Cancer Res 2007;13:49434948. 95. Fabian CJ, Kimler BF, Zalles CM, et al. Short-term breast cancer prediction by random periareolar ne-needle aspiration cytology and the Gail risk model. J Natl Cancer Inst 2000;92:12171227. 96. Milanese TR, Hartmann LC, Sellers TA, et al. Age-related lobular involution and risk of breast cancer. J Natl Cancer Inst 2006;98:16001607. 97. Vierkant RA, Hartmann LC, Pankratz VS, et al. Lobular involution: localized phenomenon or eld effect? Breast Cancer Res Treat 2009;117:193196. 98. Veronesi U, De Palo G, Marubini E, et al. Randomized trial of fenretinide to prevent second breast malignancy in women with early breast cancer. J Natl Cancer Inst 1999; 91:18471856. 99. Veronesi U, Mariani L, Decensi A, et al. Fifteen-year results of a randomized phase III trial of fenretinide to prevent second breast cancer. Ann Oncol 2006;17:10651071. 100. Calle EE, Rodriguez C, Walker-Thurmond K, et al. Overweight, obesity, and mortality from cancer in a prospectively studied cohort of U. S. Adults. N Engl J Med 2003;348: 16251638. 101. Reeves GK, Pirie K, Beral V, et al. Cancer incidence and mortality in relation to body mass index in the million women study: cohort study. Br Med J 2007;335:11341139. 102. McTiernan A, Kooperberg C, White E, et al. Recreational physical activity and the risk of breast cancer in postmenopausal women: the Womens Health Initiative Cohort study. JAMA 2003;290:13311336. 103. Allen NE, Beral V, Casabonne D, et al. Moderate alcohol intake and cancer incidence in women. J Natl Cancer Inst 2009;101:296305. 104. Decensi A, Galli A, Veronesi U. HRT opposed to low-dose tamoxifen (HOT study): rationale and design. Recent Results Cancer Res 2003;163:104111; discussion 2646. 105. Vogel VG, Costantino JP, Wickerham DL, et al. National Surgical Adjuvant Breast and Bowel Project update: prevention trials and endocrine therapy of ductal carcinoma in situ. Clin Cancer Res 2003;9:495S501S. 106. Cuzick J. Aromatase inhibitors for breast cancer prevention. J Clin Oncol 2005;23: 16361643. 107. Richardson H, Johnston D, Pater J, et al. The National Cancer Institute of Canada Clinical Trials Group MAP.3 trial: an international breast cancer prevention trial. Curr Oncol 2007;14:8996. 108. Cuzick J. Aromatase inhibitors in prevention: data from the ATAC (Arimidex, Tamoxifen Alone or in Combination) trial and the design of IBIS-II (the Second International Breast Cancer Intervention Study). Recent Results Cancer Res 2003;163:96103; discussion 2646. 109. Marchetti P, Di Rocco CZ, Ricevuto E, et al. Reducing breast cancer incidence in familial breast cancer: overlooking the present panorama. Ann Oncol 2004;15(suppl 1): I27I34.

68. Day R, Ganz PA, Costantino JP, et al. Health-related quality of life and tamoxifen in breast cancer prevention: a report from the National Surgical Adjuvant Breast and Bowel Project P-1 study. J Clin Oncol 1999;17:26592669. 69. Day R, Ganz PA, Costantino JP. Tamoxifen and depression: more evidence from the National Surgical Adjuvant Breast and Bowel Projects breast cancer prevention (P-1) randomized study. J Natl Cancer Inst 2001;93:16151623. 70. Port ER, Montgomery LL, Heerdt AS, et al. Patient reluctance toward tamoxifen use for breast cancer primary prevention. Ann Surg Oncol 2001;8:580585. 71. Tchou J, Hou N, Rademaker A, et al. Acceptance of tamoxifen chemoprevention by physicians and women at risk. Cancer 2004;100:18001806. 72. Ettinger B, Black DM, Mitlak BH, et al. Reduction of vertebral fracture risk in postmenopausal women with osteoporosis treated with raloxifene: results from a 3-year randomized clinical trial. Multiple Outcomes of Raloxifene Evaluation (MORE) investigators. JAMA 1999;282:637645; Erratum, JAMA 1999;282:2124. 73. Martino S, Cauley JA, Barrett-Connor E, et al. Continuing Outcomes Relevant to Evista: breast cancer incidence in postmenopausal osteoporotic women in a randomized trial of raloxifene. J Natl Cancer Inst 2004;96:17511761. 74. Vogel VG, Costantino JP, Wickerham DL, et al. Effects of tamoxifen vs raloxifene on the risk of developing invasive breast cancer and other disease outcomes: the NSABP Study of Tamoxifen and Raloxifene (STAR) P-2 trial. JAMA 2006;295(23):27272741. 75. Vogel, VG, Costantino, J P, Wickerham, D L, et al. Update of the National Surgical Adjuvant Breast and Bowel Project Study of Tamoxifen and Raloxifene (STAR) P-2 Trial: Preventing Breast Cancer. Cancer Prev Res (Phila Pa). 76. King MC, Wieand S, Hale K, et al. Tamoxifen and breast cancer incidence among women with inherited mutations in BRCA1 and BRCA2: National Surgical Adjuvant Breast and Bowel Project (NSABP-P1) breast cancer prevention trial. JAMA 2001;286:22512256. 77. Narod SA, Brunet JS, Ghadirian P, et al. Tamoxifen and risk of contralateral breast cancer in BRCA1 and BRCA2 mutation carriers: a casecontrol study. Hereditary Breast Cancer Clinical Study Group. Lancet 2000;356:18761881. 78. Lakhani SR, Van De Vijver MJ, Jacquemier J, et al. The pathology of familial breast cancer: predictive value of immunohistochemical markers estrogen receptor, progesterone receptor, her-2, and p53 in patients with mutations in BRCA1 and BRCA2. J Clin Oncol 2002;20:23102318. 79. Meijers-Heijboer H, van Geel B, van Putten WL, et al. Breast cancer after prophylactic bilateral mastectomy in women with a BRCA1 or BRCA2 mutation. N Engl J Med 2001;345: 159164. 80. Kauff ND, Satagopan JM, Robson ME, et al. Risk-reducing salpingo-oophorectomy in women with a BRCA1 or BRCA2 mutation. N Engl J Med 2002;346:16091615. 81. Rebbeck TR, Levin AM, Eisen A, et al. Breast cancer risk after bilateral prophylactic oophorectomy in BRCA1 mutation carriers. J Natl Cancer Inst 1999;91:14751479. 82. Hartmann LC, Schaid DJ, Woods JE, et al. Efcacy of bilateral prophylactic mastectomy in women with a family history of breast cancer. N Engl J Med 1999;340:7784. 83. Baum M, Budzar AU, Cuzick J, et al. Anastrozole alone or in combination with tamoxifen versus tamoxifen alone for adjuvant treatment of postmenopausal women with early breast cancer: first results of the ATAC randomised trial. Lancet 2002;359: 21312139. 84. Coombes RC, Hall E, Gibson LJ, et al. A randomized trial of exemestane after two to three years of tamoxifen therapy in postmenopausal women with primary breast cancer. N Engl J Med 2004;350:10811092. 85. Goss PE, Ingle JN, Martino S, et al. Randomized trial of letrozole following tamoxifen as extended adjuvant therapy in receptor-positive breast cancer: updated findings from NCIC CTG MA.17. J Natl Cancer Inst 2005;97:12621271. 86. Dunn BK, Ryan A. Phase 3 trials of aromatase inhibitors for breast cancer prevention following in the path of the selective estrogen receptor modulators. In: Bradlow HL, Carruba G, eds. Steroid Enzymes and Cancer. Blackwell, London; 2008:141161. 87. Lostumbo L, Carbine N, Wallace J, et al. Prophylactic mastectomy for the prevention of breast cancer. Cochrane Database Syst Rev 2004:CD002748.

CHAPTER

7
INTRODUCTION
Ductal carcinoma in situ (DCIS) of the breast is a heterogeneous group of lesions with diverse malignant potential and a range of treatment options. It is the most rapidly growing subgroup in the breast cancer family of disease, with more than 67,000 new cases diagnosed in the United States during 2008 (27% of all new cases of breast cancer) (1). Most new cases (90%) are nonpalpable and discovered mammographically. It is now well appreciated that DCIS is a stage in the neoplastic continuum in which most of the molecular changes that characterize invasive breast cancer are already present (2). All that remains on the way to invasion are quantitative changes in the expression of genes that have already been altered. Genes that might play a role in invasion control a number of functions, including angiogenesis, adhesion, cell motility, the composition of extracellular matrix, and more. To date, genes that are uniquely associated with invasion have not been identied. DCIS is clearly the precursor lesion for most invasive breast cancers, but not all DCIS lesions have the time or the genetic ability to progress to become invasive breast cancer (35). Therapy for DCIS ranges from simple excision to various forms of wider excision (segmental resection, quadrant resection, oncoplastic resection, etc.), all of which may or may not be followed by radiation therapy. When breast preservation is not feasible, total mastectomy, with or without immediate reconstruction, is generally performed. Since DCIS is a heterogeneous group of lesions rather than a single entity (6,7) and because patients have a wide range of personal needs that must be considered during treatment selection, it is clear that no single approach will be appropriate for all forms of the disease or for all patients. At the current time, treatment decisions are based upon a variety of measurable parameters (tumor extent, margin width, nuclear grade, the presence or absence of comedonecrosis, age, etc.), physician experience and bias, and randomized trial data, which suggest that all conservatively treated patients should be managed with postexcisional radiation therapy.

Melvin J. Silverstein

Ductal Carcinoma In Situ: An Oncoplastic Treatment Approach


Pagets disease (9,10). Today, most lesions are nonpalpable and generally detected by mammography alone. Until approximately 20 years ago, the treatment for most patients with DCIS was mastectomy. Today, almost 75% of newly diagnosed patients with DCIS are treated with breast preservation (11). In the past, when mastectomy was common, reconstruction was uncommon; if it was performed, it was generally done as a delayed procedure. Today, reconstruction for patients with DCIS treated by mastectomy is common; when it is performed, it is generally done immediately, at the time of mastectomy. In the past, when a mastectomy was performed, large amounts of skin were discarded. Today, it is considered perfectly safe to perform a skin-sparing mastectomy for DCIS and, in some instances, nipple-areola sparing-mastectomy. In the past, there was little confusion. All breast cancers were considered essentially the same, and mastectomy was the only treatment. Today, all breast cancers are different, and there is a range of acceptable treatments for every lesion. For those that choose breast conservation, there continues to be a debate as to whether radiation therapy is necessary in every case. These changes were brought about by a number of factors. Most important were increased mammographic utilization and the acceptance of breast conservation therapy for invasive breast cancer. The widespread use of mammography changed the way DCIS was detected. In addition, it changed the nature of the disease detected by allowing us to enter the neoplastic continuum at an earlier time. It is interesting to note the impact that mammography had on the Breast Center in Van Nuys, California, in terms of the number of DCIS cases diagnosed and the way they were diagnosed (12). From 1979 to 1981, the Van Nuys group treated a total of only 15 patients with DCIS, 5 per year. Only 2 lesions (13%) were nonpalpable and detected by mammography. In other words, 13 patients (87%) presented with clinically apparent disease. Two state-of-the-art mammography units and a full-time experienced radiologist were added in 1982, and the number of new DCIS cases dramatically increased to more than 30 per year, most of them nonpalpable. When a third machine was added in 1987, the number of new cases increased to 40 per year. In 1994, the Van Nuys group added a fourth mammography machine and a prone stereotactic biopsy unit. In 1998, I moved to the Norris Comprehensive Cancer Center at the University of Southern California (USC) and continued to accrue DCIS patients. In March 2008, I became director of the Breast Program at Hoag Memorial Hospital Presbyterian in Newport Beach, California, and the DCIS series continued. Analysis of the entire series of 1,411 patients through December 2008 shows that 1,242 lesions (88%) were nonpalpable (subclinical). If we look at only those diagnosed during the last 5 years that I was at the USC/Norris Cancer Center, 95% were nonpalpable.

THE CHANGING NATURE OF DUCTAL CARCINOMA IN SITU


There have been dramatic changes in the last 20 years that have affected DCIS. Before mammography was common, DCIS was rare, representing less than 1% of all breast cancer (8). Today, DCIS is common, representing 27% of all newly diagnosed cases and as much as 30% to 50% of cases of breast cancer diagnosed by mammography (1,115119). Previously, most patients with DCIS presented with clinical symptoms, such as breast mass, bloody nipple discharge, or

71

72

Section I Oncology and Oncoplastic Surgery

The second factor that changed how we think about DCIS was the acceptance of breast conservation therapy (lumpectomy, axillary node dissection, and radiation therapy) for patients with invasive breast cancer. Until 1981, the treatment for most patients with any form of breast cancer was generally mastectomy. Since that time, numerous prospective randomized trials have shown an equivalent rate of survival for selected patients with invasive breast cancer treated with breast conservation therapy (1318). Based on these results, it made little sense to continue treating less aggressive DCIS with mastectomy while treating more aggressive invasive breast cancer with breast preservation. Current data suggest that many patients with DCIS can be successfully treated with breast preservation, with or without radiation therapy. This chapter will show how easily available data can be used to help in the complex treatment selection process.

Figure 7.1. Van Nuys ductal carcinoma in situ (DCIS) classication. DCIS patients are separated into high nuclear grade (grade 3) and nonhigh nuclear grade (grades 1 and 2). Nonhigh-nucleargrade cases are then separated by the presence or absence of necrosis. Lesions in group 3 (high nuclear grade) may or may not show necrosis.

PATHOLOGY
CLASSIFICATION Although there is no universally accepted histopathologic classication, most pathologists divide DCIS into ve major architectural subtypes (papillary, micropapillary, cribriform, solid, and comedo), often comparing the first four (noncomedo) with comedo (6,19,20). Comedo DCIS is frequently associated with high-nuclear-grade (6,1921), aneuploidy, a higher proliferation rate (22), HER2/neu gene amplification or protein overexpression (2327), and clinically more aggressive behavior (2831). Noncomedo lesions tend to be just the opposite. The division by architecture alone, comedo versus noncomedo, is an oversimplication and does not work if the purpose of the division is to sort the patients into those with a high risk of local recurrence versus those with a low risk. It is not uncommon for high-nuclear-grade noncomedo lesions to express markers similar to those of high-grade comedo lesions and to have a risk of local recurrence similar to comedo lesions. Adding to the confusion is the fact that mixtures of various architectural subtypes within a single biopsy specimen are common. In my series, more than 70% of all lesions had signicant amounts of two or more architectural subtypes, making division into a predominant architectural subtype problematic. Regarding comedo DCIS, there is no uniform agreement among pathologists of exactly how much comedo DCIS needs to be present to consider the lesion a comedo DCIS. Although it is clear that lesions exhibiting a predominant high-grade comedo DCIS pattern are generally more aggressive and more likely to recur if treated conservatively than are low-grade noncomedo lesions, architectural subtyping does not reect current biologic thinking. Rather, it is the concept of nuclear grading that has assumed importance. Nuclear grade is a better biologic predictor than architecture, and therefore it has emerged as a key histopathologic factor for identifying aggressive behavior (28,3135). In 1995, the Van Nuys group introduced a new pathologic DCIS classication (36) based on the presence or absence of high-nuclear-grade and comedo-type necrosis (the Van Nuys classication). The Van Nuys group chose high nuclear grade as the most important factor in their classication because there was general agreement that patients with high-nuclear-grade lesions were more likely to recur at a higher rate and in a shorter time period after breast conservation than patients with

low-nuclear-grade lesions (28,31,34,3739). Comedo-type necrosis was chosen because its presence also suggests a poorer prognosis (40,41) and it is easy to recognize (42). The pathologist, using standardized criteria as noted below, rst determines whether the lesion is high nuclear grade (nuclear grade 3) or nonhigh nuclear grade (nuclear grade 1 or 2). Then, the presence or absence of necrosis is assessed in the nonhigh-grade lesions. This results in three groups (Fig. 7.1). Nuclear grade is scored by previously described methods (36). Essentially, low-grade nuclei (grade 1) are dened as nuclei 1 to 1.5 red blood cells in diameter with diffuse chromatin and unapparent nucleoli. Intermediate nuclei (grade 2) are dened as nuclei 1 to 2 red blood cells in diameter with coarse chromatin and infrequent nucleoli. High-grade nuclei (grade 3) are dened as nuclei with a diameter greater than 2 red blood cells, with vesicular chromatin, and one or more nucleoli. In the Van Nuys classication, no requirement is made for a minimum or specic amount of high-nuclear-grade DCIS, nor is any requirement made for a minimum amount of comedo-type necrosis. Occasional desquamated or individually necrotic cells are ignored and are not scored as comedotype necrosis. The most difcult part of most classications is nuclear grading, particularly the intermediate-grade lesions. The subtleties of the intermediate-grade lesion are not important to the Van Nuys classication; only nuclear grade 3 need be recognized. The cells must be large and pleomorphic, lack architectural differentiation and polarity, have prominent nucleoli and coarse, clumped chromatin, and generally show mitoses (36,40). The Van Nuys classication is useful because it divides DCIS into three different biologic groups with different risks of local recurrence after breast conservation therapy (Fig. 7.2). This pathologic classication, when combined with tumor size, age, and margin status, is an integral part of the USC/Van Nuys Prognostic Index (USC/VNPI), a system that will be discussed in detail. PROGRESSION TO INVASIVE BREAST CANCER Which DCIS lesions will become invasive, and when will that happen? These are the most important questions in the DCIS eld. There is intense molecular genetic study and knowledge

Chapter 7 Ductal Carcinoma In Situ

73

can be expected with long-term follow-up of patients with lobular carcinoma in situ, a disease that most clinicians are willing to treat with careful clinical follow-up. In addition, these patients were treated with biopsy only. No attempt was made to excise these lesions with a clear surgical margin. The natural history of low-grade DCIS can extend over 40 years and is markedly different from that of high-grade DCIS. MICROINVASION The incidence of microinvasion is difficult to quantitate because until recently there was no formal and universally accepted denition of exactly what constitutes microinvasion. The 1997 edition of AJCC Cancer Staging Manual (5th ed.) carried the first official definition of what is now classified as pT1mic and read as follows (114):
Microinvasion is the extension of cancer cells beyond the basement membrane into adjacent tissues with no focus more than 0.1 cm in greatest dimension. When there are multiple foci of microinvasion the size of only the largest focus is used to classify the microinvasion (do not use the sum of all individual foci). The presence of multiple foci of microinvasion should be noted, as it is with multiple larger invasive carcinomas.

Figure 7.2. Probability of local recurrencefree survival for 926


breast conservation patients using the Van Nuys ductal carcinoma in situ pathologic classication.

regarding the progression of normal breast epithelium through hyperplastic and atypical hyperplastic changes to DCIS and then to invasive breast cancer. Most of the genetic and epigenetic changes present in invasive breast cancer are already present in DCIS. No genes uniquely associated with invasive cancer have been identied (2,11). As DCIS progresses to invasive breast cancer, quantitative changes in the expression of genes related to angiogenesis, adhesion, cell motility, and the composition of the extracellular matrix may occur (2,11). Using gene-array technology, researchers are attempting to identify high-risk patterns, which will require quicker and more aggressive treatment. Because most patients with DCIS have been treated with mastectomy, knowledge of the natural history of this disease is relatively scant. In a study of 110 consecutive, medicolegal autopsies of young and middle-aged women between the ages of 20 and 54 years, 14% were found to have DCIS (43), suggesting that the subclinical prevalence of DCIS is signicantly higher than the clinical expression of the disease. The studies of Page et al. (44,45) and Rosen et al. (46) shed light on the nontreatment of DCIS. In these studies, patients with noncomedo DCIS were initially misdiagnosed as having benign lesions and therefore went untreated. Subsequently, approximately 25% to 35% of these patients developed invasive breast cancer, generally within 10 years (44,45). Had the lesions been high-grade comedo DCIS, the invasive breast cancer rate likely would have been higher than 35% and the time to invasive recurrence shorter. With few exceptions, in both of these studies, the invasive breast carcinoma was of the ductal type and was located at the site of the original DCIS. These ndings and the fact that autopsy series have shown up to a 14% incidence of DCIS suggest that not all DCIS lesions progress to invasive breast cancer or become clinically signicant (43,47). There is far more microscopic DCIS than clinically apparent DCIS. Page and associates recently updated their series (44,45,48). Of 28 women with low-grade DCIS misdiagnosed with benign lesions and treated with biopsy between 1950 and 1968, 11 patients recurred locally with invasive breast cancer (39%). Eight patients developed recurrence within the rst 12 years. The remaining 3 were diagnosed over 23 to 42 years. Five patients developed metastatic breast cancer (18%) and died from the disease within 7 years of developing invasive breast cancer. These recurrence and mortality rates, at rst glance, seem alarmingly high. However, they are only slightly worse than what

The reported incidence of occult invasion (invasive disease at mastectomy in patients with a biopsy diagnosis of DCIS) varies greatly, ranging from as little as 2% to as much as 21% (49). This problem was addressed in the investigations of Lagios et al. (28). Lagios et al. performed a meticulous serial subgross dissection correlated with specimen radiography. Occult invasion was found in 13 of 111 mastectomy specimens from patients who had initially undergone excisional biopsy of DCIS. All occult invasive cancers were associated with DCIS greater than 45 mm in diameter; the incidence of occult invasion approached 50% for DCIS greater than 55 mm. In the study of Gump et al. (50), foci of occult invasion were found in 11% of patients with palpable DCIS but in no patients with clinically occult DCIS. These results suggest a correlation between the size of the DCIS lesion and the incidence of occult invasion. Clearly, as the size of the DCIS lesion increases, microinvasion and occult invasion become more likely. If even the smallest amount of invasion is found, the lesion should not be classied as DCIS. It is a T1mic (if the largest invasive component is 1 mm or less) with an extensive intraductal component (EIC). If the invasive component is 1.1 to 5 mm, it is a T1a lesion with EIC. If there is only a single focus of invasion, these patients do quite well. When there are many tiny foci of invasion, these patients have a poorer prognosis than expected (51). Unfortunately, the TNM staging system does not have a T category that fully reects the malignant potential of lesions with multiple foci of invasion since they are all classied by their largest single focus of invasion. MULTICENTRICITY AND MULTIFOCALITY OF DUCTAL CARCINOMA IN SITU Multicentricity is generally defined as DCIS in a quadrant other than the quadrant in which the original DCIS (index quadrant) was diagnosed. There must be normal breast tissue separating the two foci. However, denitions of multicentricity vary among investigators. Hence, the reported incidence of multicentricity also varies. Rates from 0% to 78% (7,46,52,53),

74

Section I Oncology and Oncoplastic Surgery

averaging about 30%, have been reported. Twenty years ago, the 30% average rate of multicentricity was used by surgeons as the rationale for mastectomy in patients with DCIS. Holland et al. (54) evaluated 82 mastectomy specimens by taking a whole-organ section every 5 mm. Each section was radiographed. Parafn blocks were made from every radiographically suspicious spot. In addition, an average of 25 blocks were taken from the quadrant containing the index cancer; random samples were taken from all other quadrants, the central subareolar area, and the nipple. The microscopic extension of each lesion was veried on the radiographs. This technique permitted a three-dimensional reconstruction of each lesion. This study demonstrated that most DCIS lesions were larger than expected (50% were greater than 50 mm), involved more than one quadrant by continuous extension (23%), but most important, were unicentric (98.8%). Only one of 82 mastectomy specimens (1.2%) had true multicentric distribution with a separate lesion in a different quadrant. This study suggests that complete excision of a DCIS lesion is possible due to unicentricity but may be extremely difcult due to larger than expected size. In a recent update, Holland and Faverly reported whole-organ studies in 119 patients, 118 of whom had unicentric disease (55). This information, when combined with the fact that most local recurrences are at or near the original DCIS, suggests that the problem of multicentricity per se is not important in the DCIS treatment decision-making process. Multifocality is dened as separate foci of DCIS within the same ductal system. The studies of Holland et al. (54,55) and Noguchi et al. (56) suggest that a great deal of multifocality may be artifactual, resulting from looking at a threedimensional arborizing entity in two dimensions on a glass slide. It would be analogous to saying that the branches of a tree were not connected if the branches were cut at one plane, placed separately on a slide, and viewed in cross section (44). Multifocality may be due to small gaps of DCIS or skip areas within ducts as described by Faverly et al. (39).

Figure 7.3. Mediolateral mammography in a 43-year-old woman


showing irregular branching calcications. Histopathology showed high-grade comedo ductal carcinoma in situ, Van Nuys group 3.

DETECTION AND DIAGNOSIS


The importance of quality mammography cannot be overemphasized. Currently, most patients with DCIS (more than 90%) present with nonpalpable lesions. A few percent are detected as random findings during a biopsy for a breast thickening or some other benign brocystic change; most lesions, however, are detected by mammography. The most common mammographic ndings are microcalcications, frequently clustered and generally without an associated soft-tissue abnormality. More than 80% of DCIS patients exhibit microcalcications on preoperative mammography. The patterns of these microcalcications may be focal, diffuse, or ductal, with variable size and shape. Patients with comedo DCIS tend to have casting calcications. These are linear, branching, and bizarre and are almost pathognomonic for comedo DCIS (57) (Fig. 7.3). Almost all comedo lesions have calcications that can be visualized on mammography. Thirty-two percent of noncomedo lesions in my series did not have mammographic calcications, making them more difcult to nd and the patients more difcult to follow, if treated conservatively. When noncomedo lesions are calcied, they tend to have ne, granular, powdery calcications or crushed stonelike calcications (Fig. 7.4).

A major problem confronting surgeons relates to the fact that calcications do not always map out the entire DCIS lesion, particularly those of the noncomedo type. Even though all the calcications are removed, in some cases, noncalcied DCIS may be left behind. Conversely, in some patients, the majority of the calcications are benign and map out a lesion bigger than the true DCIS lesion. In other words, the DCIS lesion may be smaller than, larger than, or the same size as the calcications that lead to its identication. Calcications more accurately approximate the size of high-grade comedo lesions than low-grade noncomedo lesions (54). Before mammography was common or of good quality, most DCIS was usually clinically apparent, diagnosed by palpation or inspection; it was gross disease. Gump et al. (50) divided DCIS by method of diagnosis into gross and microscopic disease. Similarly, Schwartz et al. (29) divided DCIS into two groups: clinical and subclinical. Both groups of researchers thought patients presenting with a palpable mass, a nipple discharge, or Pagets disease of the nipple required more aggressive treatment. Schwartz believed that palpable DCIS should be treated as though it were an invasive lesion. He suggested that the pathologist simply has not found the area of invasion. Although

Figure 7.4. Crushed stonetype calcications.

Chapter 7 Ductal Carcinoma In Situ

75

it makes perfect sense to believe that the change from nonpalpable to palpable disease is a poor prognostic sign, our group has not been able to demonstrate this for DCIS. In our series, when equivalent patients (by size and nuclear grade) with palpable and nonpalpable DCIS were compared, they did not differ in the rate of local recurrence or mortality. If a patients mammogram shows an abnormality, most likely it will be microcalcications, but it could be a nonpalpable mass or a subtle architectural distortion. At this point, additional radiologic workup needs to be performed. This may include compression mammography, magnication views, or ultrasonography. Magnetic resonance imaging (MRI) has become increasingly popular to map out the size and shape of biopsy-proven DCIS lesions or invasive breast cancers. I obtain a preoperative MRI on every patient with a diagnosis of breast cancer. BIOPSY AND TISSUE HANDLING If radiologic workup shows an occult lesion that requires biopsy, there are multiple approaches: ne-needle aspiration biopsy (FNAB), core biopsy (with various types and sizes of needles), and directed surgical biopsy using guide wires or radioactivity. FNA is generally of little help for nonpalpable DCIS. With FNA, it is possible to obtain cancer cells, but because there is insufcient tissue, there is no architecture. Thus, although the cytopathologist can say that malignant cells are present, the cytopathologist generally cannot say whether the lesion is invasive. Stereotactic core biopsy became widely available in the early 1990s, and it is now widely used. Dedicated digital tables make this a precise tool in experienced hands. Currently, large-gauge (11 gauge or larger) vacuum-assisted needles are the tools of choice for diagnosing DCIS. Ultrasound-guided biopsy also became very popular in the 1990s but is of less value for DCIS since most DCIS lesions do not present with a mass that can be visualized by ultrasound. All suspicious microcalcications should be evaluated by ultrasound since a mass will be found in 5% to 15% of cases (58). Open surgical biopsy should only be used if the lesion cannot be biopsied using minimally invasive techniques. This should be a rare event with current image-guided biopsy techniques (58,59) and occur in less than 5% of cases. Needle localization segmental resection should be a critical part of the treatment not the diagnosis. Whenever needle localization excision is performed, whether for diagnosis or treatment, intraoperative specimen radiography and correlation with the preoperative mammogram should be performed. Margins should be inked or dyed, and specimens should be serially sectioned at 3- to 4-mm intervals. The tissue sections should be arranged and processed in sequence. Pathologic reporting should include a description of all architectural subtypes, a determination of nuclear grade, an assessment of the presence or absence of necrosis, the measured size or extent of the lesion, and the margin status with measurement of the closest margin. Tumor size should be determined by direct measurement or ocular micrometry from stained slides for smaller lesions. For larger lesions, a combination of direct measurement and estimation, based on the distribution of the lesion in a sequential series of slides, should be used. The proximity of DCIS to an inked margin should be determined by direct measurement or ocular micrometry. The closest single distance between any

involved duct containing DCIS and an inked margin should be reported. If the lesion is large and the diagnosis unproven, either stereotactic or ultrasound-guided vacuum-assisted biopsy should be the rst step. If the patient is motivated for breast conservation, a multiple-wiredirected oncoplastic excision can be planned. This will give the patient her best chance at two opposing goals: clear margins and good cosmesis. The best chance at completely removing a large lesion is with a large initial excision. The best chance at good cosmesis is with a small initial excision. It is the surgeons job to optimize these opposing goals. A large-quadrant resection should not be performed unless there is histologic proof of malignancy. This type of resection may lead to breast deformity, and should the diagnosis prove to be benign, the patient will be unhappy. Removal of nonpalpable lesions is best performed by an integrated team of surgeon, radiologist, and pathologist. The radiologist who places the wires and interprets the specimen radiograph must be experienced, as must the surgeon who removes the lesion and the pathologist who processes the tissue.

TREATMENT
For most patients with DCIS, there will be no single correct treatment. There will generally be a choice. The choices, although seemingly simple, are not. As the choices increase and become more complicated, frustration increases for both the patient and her physician (60,61). COUNSELING THE PATIENT WITH BIOPSYPROVEN DUCTAL CARCINOMA IN SITU It is never easy to tell a patient that she has breast cancer. But is DCIS really cancer? From a biologic point of view, DCIS is unequivocally cancer. When we think of cancer, however, we generally think of a disease that, if untreated, runs an inexorable course toward death. That is certainly not the case with DCIS (45). We must emphasize to the patient that she has a borderline cancerous lesion, a preinvasive lesion, which at this time is not a threat to her life. In our series of 1,411 patients with DCIS, the breast cancerspecic mortality rate is 0.5%. Numerous other DCIS series (6267) conrm an extremely low mortality rate. Patients often ask why there is any mortality rate at all if DCIS is truly a noninvasive lesion. If DCIS recurs as an invasive lesion and the patient goes on to die from metastatic breast cancer, the source of the metastases is clear. But what about the patient who undergoes mastectomy and sometime later develops metastatic disease, or a patient who is treated with breast preservation who never develops a local invasive recurrence but still dies of metastatic breast cancer? These latter patients probably had an invasive focus with established metastases at the time of their original treatment, but the invasive focus was missed during routine histopathologic evaluation. No matter how carefully and thoroughly a specimen is examined, it is still a sampling process, and a 1- to 2-mm focus of invasion can be missed. One of the most frequent concerns expressed by patients once a diagnosis of cancer has been made is the fear that the cancer has spread. We are able to assure patients with DCIS that no invasion was seen microscopically and the likelihood of systemic spread is minimal.

76

Section I Oncology and Oncoplastic Surgery

The patient needs to be educated that the term breast cancer encompasses a multitude of lesions of varying degrees of aggressiveness and lethal potential. The patient with DCIS needs to be reassured that she has a minimal lesion and that she is likely going to need some additional treatment, which may include surgery, radiation therapy, an antiestrogen, or some combination. She needs reassurance that she will not need chemotherapy, that her hair will not fall out, and that it is highly unlikely that she will die from this lesion. She will, of course, need careful clinical follow-up. ENDPOINTS FOR PATIENTS WITH DUCTAL CARCINOMA IN SITU When evaluating the results of treatment for patients with breast cancer, a variety of endpoints must be considered. Important endpoints include local recurrence (both invasive and DCIS), regional recurrence (such as the axilla), distant recurrence, breast cancerspecic survival, overall survival, and quality of life. The importance of each endpoint varies depending on whether the patient has DCIS or invasive breast cancer When treating invasive cancer, the most important endpoints are distant recurrence and breast cancerspecic survival, in other words, living with or dying from breast cancer. For invasive breast cancer, a variety of different systemic treatments have been shown to signicantly improve survival. These include a wide range of chemotherapeutic regimens and endocrine treatments. Variations in local treatment were incorrectly thought not to affect survival (18,68). They do, however, affect local recurrence. Recently the literature has shown that for every four local recurrences prevented, one breast cancer death is prevented (69). DCIS is similar to invasive breast cancer in that variations in local treatment affect local recurrence, but no study has shown a signicant difference in distant disease-free or breast cancer specic survival, regardless of any treatment (systemic or local), and no study is likely to show a difference since there are so few breast cancer deaths in patients with pure DCIS. The most important outcome measure, breast cancerspecic survival, is essentially the same no matter what local or systemic treatment is given. Consequently, local recurrence has become the most commonly used endpoint when evaluating treatment for patients with DCIS. A meta-analysis of four randomized DCIS trials comparing excision plus radiation therapy versus excision alone was published in 2007. It contained 3,665 patients. Radiation therapy decreased local control by a statistically signicant 60%, but overall survival was slightly worse in the radiotherapy group, with a relative risk of 1.08 (66). These data are dissimilar to those of the Early Breast Cancer Trialists Collaborative Group and deserve further analysis (69). Half of the recurrences in the meta-analysis were DCIS and could not possibly affect survival. Of the remaining invasive recurrences, 80% to 90% were cured by early detection and treatment. This should result in a slight trend toward a lower survival for the excision-alone group, but exactly the opposite was seen, a nonsignicant trend toward a better survival. The authors of the meta-analysis felt that with longer follow-up, the higher local recurrence rate for excision alone will likely result in a lower overall survival at some point in time. For the time being, however, that has not happened, and a detrimental effect secondary to radiation therapy must be considered a possibility.

Local recurrences are clearly important to prevent in patients treated with DCIS. They are demoralizing. They often lead to mastectomy and, theoretically, if they are invasive, they increase the stage of the patient and are a threat to life. However, protecting DCIS patients from local recurrence must be balanced against the potential detrimental effects of the treatments given. Following treatment for DCIS, 40% to 50% of all local recurrences are invasive. About 10% to 20% of DCIS patients who develop local invasive recurrences develop distant metastases and die from breast cancer (70,71). Long term, this could translate into a mortality rate of about 0% to 0.5% for patients treated with mastectomy, 1% to 2% for conservatively treated patients who receive radiation therapy (if there is no mortality associated with radiation therapy), and 2% to 3% for patients treated with excision alone. In order to save their breasts, many patients are willing to accept this theoretical, and as of now statistically unproven, small absolute risk associated with breast conservation therapy.

TREATMENT OPTIONS

Mastectomy
Mastectomy is, by far, the most effective treatment available for DCIS if our goal is simply to prevent local recurrence. Most mastectomy series reveal local recurrence rates of approximately 1%, with mortality rates close to zero (72). In my series, I have had only 1 breast cancer death among 485 patients treated with mastectomy (0.2%). However, mastectomy is an aggressive form of treatment for patients with DCIS. It clearly provides a local recurrence benet but only a theoretical survival benet. It is, therefore, often difcult to justify mastectomy, particularly for otherwise healthy women with screen-detected DCIS, during an era of increasing utilization of breast conservation for invasive breast carcinoma. Mastectomy is indicated in cases of true multicentricity (multiquadrant disease) and when a unicentric DCIS lesion is too large to excise with clear margins and an acceptable cosmetic result. Genetic positivity to one of the breast cancerassociated genes (BRCA1, BRCA2) is not an absolute contraindication to breast preservation, but many patients who are genetically positive and who develop DCIS seriously consider bilateral mastectomy and oophorectomy.

Breast Conservation
The most recent Surveillance Epidemiology and End Results (SEER) data reveal that 74% of patients with DCIS are treated with breast conservation. While breast conservation is now widely accepted as the treatment of choice for DCIS, not all patients are good candidates. Certainly, there are patients with DCIS whose local recurrence rate with breast preservation is so high (based on factors that will be discussed later in this chapter) that mastectomy is clearly a more appropriate treatment. However, the majority of women with DCIS diagnosed currently are candidates for breast conservation. Clinical trials have shown that local excision and radiation therapy in patients with negative margins can provide excellent rates of local control (62,6567,7376). However, even radiation therapy may be overly aggressive since many cases of DCIS may not

Chapter 7 Ductal Carcinoma In Situ

77

recur or progress to invasive carcinoma when treated by excision alone (28,45,7780).

Reasons to Consider Excision Alone


There are a number of lines of reasoning that suggest that excision alone may be an acceptable treatment for selected patients with DCIS. 1. The prevalent use of excision. Excision alone is already common in spite of the randomized data that suggest that all conservatively treated patients benet from radiation therapy. The 2003 SEER data indicated that excision alone was being used as complete treatment for DCIS in 35% of all DCIS patients. American doctors and patients have embraced the concept of excision alone. 2. Anatomic considerations. Evaluation of mastectomy specimens using the serial subgross tissue processing technique reveals that most DCIS is unicentric (involves a single breast segment and is radial in its distribution) (35,39,54, 55,81,82). This means that in many cases, it is possible to excise the entire lesion with a segment or quadrant resection. Since DCIS, by denition, is not invasive and has not metastasized, it can be thought of in Halstedian terms. Complete excision should cure the patient without any additional therapy. Faverly et al. showed that if 10-mm margins are achieved in all directions, the likelihood of residual DCIS is less than 10% (39). 3. Biologic factors. Some DCIS is simply not aggressive, for example, small, well-excised low-grade lesions bordering on atypical ductal hyperplasia. Lesions like this carry a low potential for development into an invasive lesion, about 1% per year at most (44,45,48,77,83,84). This is only slightly more than lobular carcinoma in situ (LCIS), a lesion that is routinely treated with careful clinical follow-up. 4. The possibility of pathology errors. The differences between atypical ductal hyperplasia and low-grade DCIS may be subtle. It is not uncommon for atypical ductal hyperplasia to be called DCIS. Such patients treated with radiation therapy are indeed cured of their DCIS. 5. Evidence from prospective, randomized data. The prospective randomized DCIS trials show no difference in breast cancerspecific survival or overall survival regardless of treatment after excision with or without breast irradiation (62,6567,76). If this is true, why not strive for the least aggressive treatment? 6. Potential harmfulness of radiation therapy. Numerous studies have shown that radiation therapy for breast cancer may increase mortality from both lung cancer and cardiovascular disease (8589). Current radiotherapy techniques that use computed tomography planning make every attempt to spare the heart and lungs from radiation exposure, but long-term data are not available. If there is no proof that breast irradiation for patients with DCIS improves survival and there is proof that radiation therapy may cause harm, it makes perfect sense to spare patients from this potentially dangerous treatment whenever possible. 7. Drawbacks of radiation therapy. Radiation therapy is expensive, time consuming, and accompanied by signicant side effects in a small percentage of patients (cardiac, pulmonary, etc.) (90). Radiation brosis continues to occur, but it is less common with current techniques than it was during the 1980s. Radiation brosis changes the texture of

8.

9.

10.

11.

the breast and skin, makes mammographic follow-up more difcult, and may result in delayed diagnosis if there is a local recurrence. Recurrence issues. Some series show that there are more invasive recurrences in irradiated patients than in nonirradiated patients. In our series, 34% of excision-only patients who recurred did so with invasive disease, whereas 53% of irradiated patients who recurred did so with invasive disease (p 0.01). This is true in the series of Schwartz (80) and Wong et al. (91). In our series, the median time to recur after excision alone was 23 months, while after excision and irradiation, it was 58 months (p 0.01). This delay in the diagnosis of recurrence may contribute to the increased rate of local invasive recurrence in irradiated patients. Future considerations. If radiation therapy is given for the initial DCIS, it cannot be given again at a later time if there is a small invasive recurrence. In general, in favorable patients, I prefer to withhold radiation therapy initially and only give it to the few that ultimately recur with invasive disease. The use of radiation therapy with its accompanying skin and vascular changes make skin-sparing mastectomy, if needed in the future, more difcult to perform. Patient selection. Using commonly available histopathologic parameters, we can do better than the gold standard for local recurrence established by the prospective randomized trials. The gold standard for irradiated patients is a 16% local recurrence rate at 12 years. This was established by the NSABP B-17 trial (62,7375). Using tools such as the USC/Van Nuys Prognostic Index, it is possible to select patients with low scores ranging from 4 to 6. These patients recur at a rate of 10% or less at 12 years without radiation therapy. General acceptance. Finally, the 2008 National Comprehensive Cancer Network (NCCN) guidelines added excision without radiation therapy (excision alone) as an acceptable treatment for selected patients with low risk of recurrence (92). Excision alone is now accepted and mainstream for favorable patients with DCIS.

DISTANT DISEASE AND DEATH


When a patient with DCIS previously treated by any modality develops a local invasive recurrence followed by distant disease and death due to breast cancer, this stepwise Halstedian progression makes sense. The patient has been increased in stage by her local invasive recurrence. The invasive recurrence becomes the source of the metastatic disease, and death is now a possibility. In contrast, when a previously treated patient with DCIS develops distant disease and there has been no invasive local recurrence, a completely different sequence of events must be postulated. This sequence implies that invasive disease was present within the original lesion but was never discovered and was already metastatic at the time of the original diagnosis. The best way to avoid missing an invasive cancer is with complete sequential tissue processing at the time the original lesion is treated. Nevertheless, even the most extensive evaluation may miss a tiny focus of invasion. If, during histopathologic evaluation, even the tiniest invasive component is found, this patient can no longer be classied as having DCIS. She has invasive breast cancer, and she

78

Section I Oncology and Oncoplastic Surgery

needs to be treated as such. She will need sentinel node biopsy, radiation therapy if treated conservatively, and appropriate medical oncologic consultation and aftercare.

THE PROSPECTIVE RANDOMIZED TRIALS


All of the prospective randomized trials have shown a signicant reduction in local recurrence for patients treated with radiation therapy compared with excision alone, but no trial has reported a survival benet regardless of treatment (62,65, 66,7376,93,94). Only one trial compared mastectomy with breast conservation for patients with DCIS, and the data were only incidentally accrued. The NSABP performed protocol B-06, a prospective randomized trial for patients with invasive breast cancer (52,95). There were three treatment arms: total mastectomy, excision of the tumor plus radiation therapy, and excision alone. Axillary nodes were removed regardless of the treatment assignment. During central slide review, a subgroup of 78 patients was conrmed to have pure DCIS without any evidence of invasion (52). After 83 months of follow-up, the percentages of patients with local recurrences were as follows: 0% for mastectomy, 7% for excision plus radiation therapy, and 43% for excision alone (96). In spite of these large differences in the rate of local recurrence for each different treatment, there was no difference among the three treatment groups in breast cancerspecic survival. In contrast to the lack of trials comparing mastectomy with breast conservation, a number of prospective randomized trials comparing excision plus radiation therapy with excision alone for patients with DCIS are ongoing (90). Four have been published: the NSABP (protocol B-17) (73), the European Organization for Research and Treatment of Cancer (EORTC) protocol 10853 (76), the United Kingdom, Australia, New Zealand DCIS Trial (UK Trial) (65), and the Swedish Trial (67). The results of NSABP B-17 were updated in 1995 (94), 1998 (75), 1999 (74), and 2001 (62). In this study, more than 800 patients with DCIS excised with clear surgical margins were randomized into two groups: excision alone versus excision plus radiation therapy. The main endpoint of the study was local recurrence, invasive or noninvasive (DCIS). The denition of a clear margin was nontransection of the DCIS. In other words, only a fat or brous cell needed to be present between DCIS and the inked margin to call the margin clear. Many margins, of course, were likely much wider. After 12 years of follow-up, there was a statistically signicant 50% decrease in local recurrence of both DCIS and invasive breast cancer in patients treated with radiation therapy. The overall local recurrence rate for patients treated by excision alone was 32% at 12 years. For patients treated with excision plus breast irradiation, it was 16%, a relative benet of 50% (62). There was no difference in distant disease-free or overall survival in either arm. These updated data led the NSABP to conrm their 1993 position and to continue to recommend postoperative radiation therapy for all patients with DCIS who chose to save their breasts. This recommendation was clearly based primarily on the decreased local recurrence rate for those treated with radiation therapy and secondarily on the potential survival advantage it might confer.

The early results of B-17 in favor of radiation therapy for patients with DCIS led the NSABP to perform protocol B-24 (74). In this trial, more than 1,800 patients with DCIS were treated with excision and radiation therapy and then randomized to receive either tamoxifen or placebo. After 7 years of follow-up, 11% of patients treated with placebo had recurred locally, whereas only 8% of those treated with tamoxifen had recurred (62). The difference, while small, was statistically signicant for invasive local recurrence but not for noninvasive (DCIS) recurrence. Data presented at the 2002 San Antonio Breast Cancer Symposium suggested that the ipsilateral benet was seen only in estrogen receptorpositive patients (97). Again, there was no difference in distant disease-free or overall survival in either arm of the B-24 trial. The EORTC results were published in 2000 (76,93). This study was essentially identical to B-17 in design and margin definition. More than 1,000 patients were included. The data were updated in 2006 (98). After 10 years of follow-up, 15% of patients treated with excision plus radiation therapy had recurred locally, compared with 26% of patients treated with excision alone, results similar to those obtained by the NSABP at the same point in their trial. As in the B-17 trial, there was no difference in distant disease-free or overall survival in either arm of the EORTC trial. In the initial report, there was a statistically signicant increase in contralateral breast cancer in patients who were randomized to receive radiation therapy. This was not maintained when the data were updated. The UK Trial was published in 2003 (65). This trial, which involved more than 1,600 patients, performed a two by two study in which patients could be randomized into two separate trials within a trial. The patients and their doctors chose whether to be randomized in one or both studies. After excision with clear margins (same nontransection denition as the NSABP), patients were randomized to receive radiotherapy (yes or no) and/or to tamoxifen versus placebo. This yielded four subgroups: excision alone, excision plus radiation therapy, excision plus tamoxifen, and excision plus radiation therapy plus tamoxifen. Those who received radiation therapy showed a statistically signicant decrease in ipsilateral breast tumor recurrence similar in magnitude to the ones shown by the NSABP and EORTC. Contrary to the ndings of the NSABP, there was no signicant benet from tamoxifen. As with the NSABP and the EORTC, there was no benet in terms of survival in any arm of the UK DCIS study. The Swedish DCIS Trial randomized 1,046 patients into two groups: excision alone versus excision plus radiation therapy. Microscopically clear margins were not mandatory. Twenty-two percent of patients had microscopically unknown or involved margins. Radiation therapy resulted in a 67% reduction in local recurrence rate with a median follow-up of 5.2 years. There were no differences in distant metastases or deaths (67). Overall, these trials supported the same conclusions. They all showed that radiation therapy decreased local recurrence by a relative 50%, and they all showed no survival benet, regardless of treatment. The only difference was that the NSABP B-24 trial showed a signicant decrease in local recurrence attributable to tamoxifen, while the UK Trial did not. With all the trials, as the amount of treatment increased, the rate of local recurrence decreased, but no matter how much treatment was increased, there was no improvement in survival. In fact, there could be a slight decrease in survival if there was a negative effect from radiation therapy (66).

Chapter 7 Ductal Carcinoma In Situ

79

LIMITATIONS OF THE PROSPECTIVE RANDOMIZED TRIALS


The randomized trials were designed to answer a single broad question: Does radiation therapy decrease local recurrence? They accomplished that goal. All clearly showed that, overall, radiation therapy decreased local recurrence, but they could not identify in which subgroups the benet was so small that the patients could be safely treated with excision alone. Many of the parameters considered important in predicting local recurrence (tumor size, margin width, nuclear grade, etc.) were not routinely collected prospectively during the randomized DCIS trials. In addition, the trials did not specically require the marking of margins or the measurement of margin width. The exact measurement of margin width was present in only 5% of the EORTC pathology reports (93). The NSABP did not require size measurements, and many of their pathologic data were determined by retrospective slide review. In the initial NSABP report, more than 40% of patients had no size measurement (73). Unfortunately, if margins were not inked and tissues not completely sampled and sequentially submitted, then these predictive data can never be determined accurately by retrospective review. The relative reduction in local recurrence seemed to be the same in all four trials: about 50% for any given subgroup at any point in time. What does this relative reduction mean? If the absolute local recurrence rate is 30% at 10 years for a given subgroup of patients treated with excision alone, radiation therapy will reduce this rate by approximately 50%, leaving a group of patients with a 15% local recurrence rate at 10 years. Radiation therapy seems indicated for a subgroup with such a high local recurrence rate. Consider a more favorable subgroup, however, a group of patients with a 6% to 8% absolute recurrence rate at 10 years. These patients receive only a 3% to 4% absolute benet. We must irradiate 100 women to see a 3% to 4% decrease in local recurrence. Here, we must ask whether the benets are worth the risks and costs involved, and we should make every attempt possible to identify low-risk subgroups. Radiation therapy is expensive and time consuming and is accompanied by signicant side effects in a small percentage of patients (cardiac, pulmonary, etc.) (90). Radiation brosis continues to occur, but it is less common with current techniques than it was during the 1980s. Radiation brosis changes the texture of the breast and skin, makes mammographic follow-up more difcult, and may result in delayed diagnosis if there is a local recurrence. The use of radiation therapy for DCIS precludes its use if an invasive recurrence develops at a later date. The use of radiation therapy with its accompanying skin and vascular changes makes skin-sparing mastectomy, if needed in the future, more difcult to perform. Most important, if we give radiation therapy for DCIS, we must assume all of these risks and costs without any proven distant disease-free or breast cancerspecic survival benets. The only proven benet will be a decrease in local recurrence. It is important, therefore, to carefully examine the need for radiation therapy in all conservatively treated patients with DCIS. The NSABP agreed that all patients with DCIS may not need postexcisional radiation therapy (62). The problem is how to accurately identify those patients. If we can identify subgroups of patients with DCIS in which the probability of local recurrence after excision alone is low, they may be the patients for which the costs, risks, and side effects of radiotherapy outweigh the benets.

In spite of the randomized data that suggest that all conservatively treated patients benet from radiation therapy, American doctors and patients have embraced the concept of excision alone. The 2003 SEER data revealed that 74% of patients with DCIS were treated with breast conservation. Almost half of these conservatively treated patients were treated with excision alone. When all patients with DCIS were considered, 26% received mastectomy, 39% received excision plus radiation therapy, and 35% were treated with excision alone. It is clear that both American doctors and American patients are not blindly following the results and the recommendations of the prospective trials. Based on data and treatment trends, in 2008, the NCCN added excision alone as an alternative treatment for patients with favorable DCIS (92).

PREDICTING LOCAL RECURRENCE IN CONSERVATIVELY TREATED PATIENTS WITH DUCTAL CARCINOMA IN SITU
There is now sufcient, readily available information that can aid clinicians in differentiating patients who signicantly benet from radiation therapy after excision from those who do not. These same data can indicate patients who are better served by mastectomy because recurrence rates with breast conservation are unacceptably high even with the addition of radiation therapy. Our research (36,99102) and that of others (28,31,34,40, 41,78,79,84,94,103) have shown that various combinations of nuclear grade, the presence of comedo-type necrosis, tumor size, margin width, and age are all important factors that can be used to predict the probability of local recurrence in conservatively treated patients with DCIS. THE ORIGINAL VAN NUYS PROGNOSTIC INDEX AND ITS UPDATED VERSION, THE UNIVERSITY OF SOUTHERN CALIFORNIA/VAN NUYS PROGNOSTIC INDEX In 1995, the Van Nuys DCIS pathologic classication, based on nuclear grade and the presence or absence of comedonecrosis, was developed (36) (see Fig. 7.1). Nuclear grade and comedo-type necrosis reect the biology of the lesion, but neither alone nor together are they adequate as guidelines in the treatment decision-making process. Tumor size and margin width reect the extent of disease, the adequacy of surgical treatment, and the likelihood of residual disease and are of paramount importance. The challenge was to devise a system using these variables (all independently important by multivariate analysis) that would be clinically valid, therapeutically useful, and user-friendly. The original Van Nuys Prognostic Index (VNPI) (33,104) was devised in 1996 by combining tumor size, margin width, and pathologic classication (determined by nuclear grade and the presence or absence of comedo-type necrosis). All of these factors had been collected prospectively in a large series of DCIS patients who were selectively treated (nonrandomized) (105). A score ranging from 1 for lesions with the best prognosis to 3 for lesions with the worst prognosis was given for each of the three prognostic predictors. The objective with all three predictors was to create three statistically different subgroups for each, using local recurrence as the marker of treatment

80

Section I Oncology and Oncoplastic Surgery

failure. Cut-off points (for example, what size or margin width constitutes low, intermediate, or high risk of local recurrence) were determined statistically, using the log rank test with an optimum p-value approach.

Size Score
A score of 1 was given for small tumors 15 mm or less, a score of 2 was given for intermediate-sized tumors 16 to 40 mm, and a score of 3 was given for large tumors 41 mm or greater in diameter. The determination of size required complete and sequential tissue processing along with mammographic/pathologic correlation. Size was determined over a series of sections rather than on a single section and is the most difcult parameter to reproduce. If a 3-cm specimen is cut into ten blocks, each block is estimated to be 3 mm thick. If a lesion measuring 5 mm in maximum diameter on a single slide appears in and out of seven sequential blocks, it is estimated to be 21 mm (3 mm 7) in maximum size, not 5 mm. The maximum diameter on a single slide was used for the size measurement for most of the patients in the prospective randomized trials.

Figure 7.5. Probability of local recurrencefree survival by age


group for 926 breast conservation patients.

Margin Score
A score of 1 was given for widely clear tumor-free margins of 10 mm or more. This was often achieved by reexcision with the nding of no residual DCIS or only focal residual DCIS in the wall of the biopsy cavity. A score of 2 was given for intermediate margins of 1 to 9 mm, and a score of 3 was given for margins less than 1 mm (involved or close margins).

nostic factor in our database and that it should be added to the VNPI with a weight equal to that of the other factors (101, 102,107). An analysis of our local recurrence data by age revealed that the most appropriate break points for our data were between ages 39 and 40 years and between ages 60 and 61 years (Fig. 7.5). Based on this, a score of 3 was given to all patients 39 years old or younger, a score of 2 was given to patients aged 40 to 60 years, and a score of 1 was given to patients 61 years old or older. The new scoring system for the USC/VNPI is shown in Table 7.1. The formula for the USC/Van Nuys Prognostic Index became USC/VNPI pathologic classication score margin score size score age score Scores range from 4 to 12. The patients least likely to recur after conservative therapy had a score of 4 (small, low-grade, well-excised lesions in older women). The patients most likely to recur had a score of 12 (large, poorly excised, high-grade lesions in younger women). The probability of recurrence increased as the USC/VNPI score increased. UPDATED RESULTS USING THE UNIVERSITY OF SOUTHERN CALIFORNIA/VAN NUYS PROGNOSTIC INDEX Through December 2008, our group treated 1,411 patients with pure DCIS. A total of 485 patients were treated with mastectomy and are not included in any analysis that uses local recurrence as the endpoint. A total of 926 patients were treated with breast conservation: 585 by excision alone and 341 by excision plus

Pathologic Classication Score (36,106)


A score of 3 was given for tumors classied as group 3 (high-grade lesions), a score of 2 for tumors classied as group 2 (nonhighgrade lesions with comedo-type necrosis), and a score of 1 for tumors classied as group 1 (nonhigh-grade lesions without comedo-type necrosis). The classication is diagrammed in Figure 7.1. The formula for the original VNPI became VNPI pathologic classication score margin score size score THE UNIVERSITY OF SOUTHERN CALIFORNIA/VAN NUYS PROGNOSTIC INDEX By early 2001, a multivariate analysis at the University of Southern California revealed that age was also an independent prog-

TABLE 7.1
Score
Size (mm) Margins (mm) Pathologic classication Age (y)

University of Southern California/Van Nuys Prognostic Index (VNPI) Scoring System


1
15 10 Nonhigh grade without necrosis 61

2
1640 19 Nonhigh grade with necrosis 4060

3
41 1 High grade with or without necrosis 39

From 1 to 3 points are awarded for each of four different predictors of local breast recurrence (size, margins, pathologic classication, age). Scores for each predictor are totaled to yield a VNPI score ranging from a 4 to 12.

Chapter 7 Ductal Carcinoma In Situ

81

Figure 7.6. Probability of local recurrencefree survival by


treatment for 1,411 patients with ductal carcinoma in situ.

Figure 7.8. Probability of overall survival by treatment for 1,411


patients with ductal carcinoma in situ.

radiation therapy. The average follow-up for all patients was 87 months: 85 months for mastectomy, 111 months for excision plus radiation therapy, and 76 months for excision alone. There were 165 local failures, 74 of which (45%) were invasive. The probability of local failure was reduced, overall, by 60% if radiation therapy was given, a result almost identical with the prospective randomized trials. The local recurrencefree survival is shown by treatment in Figure 7.6. As expected, at any point in time, mastectomy had the lowest probability of local recurrence, and excision alone had the highest. Seven patients (2.5%) treated with radiation therapy developed local recurrences and distant metastases, six of whom died from breast cancer. One patient (0.2%) treated with excision alone developed local invasive recurrence and metastatic disease and died from breast cancer. Two patients with mastectomy developed distant disease after developing local invasive recurrences. One died from breast cancer. There is no statistical difference in breast cancerspecic survival (Fig. 7.7) or overall survival (Fig. 7.8) when patients treated with excision alone, excision plus irradiation, or mastectomy are compared. Seventy additional patients died from other causes without evidence of recurrent breast cancer. The 12-year actuarial overall survival, including deaths from all causes, is 90%. It is virtually the same for all three treatment groups and for all three USC/VNPI groups (Fig. 7.9). The local recurrencefree survival for all 926 breast conservation patients is shown by tumor size in Figure 7.10, by margin

width in Figure 7.11, by pathologic classication in Figure 7.2, and by age in Figure 7.5. Figure 7.12 groups patients with low (USC/VNPI 4, 5, or 6), intermediate (USC/VNPI 7, 8, or 9), or high (USC/ VNPI 10, 11, or 12) risks of local recurrence together. Each of these three groups is statistically different from one another. Patients with USC/VNPI scores of 4, 5, or 6 do not show a local recurrencefree survival benet from breast irradiation (Fig. 7.13) (p NS). Patients with an intermediate rate of local recurrence, USC/VNPI 7, 8, or 9, benet by irradiation (Fig. 7.14). There is a statistically signicant decrease in the probability of local recurrence, averaging 15% throughout the curves, for irradiated patients with intermediate USC/VNPI scores compared to those treated by excision alone (p 0.004). Figure 7.15 divides patients with a USC/VNPI of 10, 11, or 12 into those treated by excision plus irradiation and those treated by excision alone. Although the difference between the two groups is highly signicant (p 0.0005), conservatively treated DCIS patients with a USC/VNPI of 10, 11, or 12 recur at an extremely high rate even with radiation therapy.

CURRENT TREATMENT TRENDS


In the current era of evidence-based medicine, it is reasonable to interpret the prospective randomized data as support that all conservatively treated patients with DCIS should receive

Figure 7.9. Probability of breast cancerspecic survival for 926 Figure 7.7. Probability of breast cancerspecic survival by treatment for 1,411 patients with ductal carcinoma in situ. breast conservation patients grouped by modied USC/Van Nuys Prognostic Index score (4, 5, or 6 versus 7, 8, or 9 versus 10, 11, or 12).

82

Section I Oncology and Oncoplastic Surgery

Figure 7.10. Probability of local recurrencefree survival by tumor


size for 926 breast conservation patients.

Figure 7.12. Probability of local recurrencefree survival for 926 breast conservation patients grouped by USC/Van Nuys Prognostic Index score (4, 5, or 6 versus 7, 8, or 9 versus 10, 11, or 12).

postexcisional radiation therapy. However, in spite of these data, the number of patients with DCIS being treated with excision alone continues to increase. The 2003 SEER data revealed that approximately one third of all patients with DCIS in the United States were being treated with excision alone (11). As an aid to the complex treatment decision-making process, the USC/VNPI can be used as a starting point to suggest reasonable treatment options supported by local recurrence data. The USC/VNPI divides patients with DCIS into three groups with differing probabilities of local recurrence after breast-conserving surgery. Although there is an apparent treatment choice for each group (Table 7.2)excision alone for patients who score 4 to 6, excision plus radiation therapy for patients who score 7 to 9, and mastectomy for those who score 10 to 12the USC/VNPI is offered only as a guideline, a starting place for discussions with patients.

THE USE OF MARGIN WIDTH AS THE SOLE PREDICTOR OF LOCAL RECURRENCE


Determining size has always been the most difcult part of the USC/VNPI. Our method computes size over a series of sections (the overall extent) rather than on a single slide (unless the measurement on a single slide is larger) and correlates this with the mammographic ndings. For example, if a 6 mm by 4 mm DCIS appears in and out of seven consecutive sections and the

blocks are on average 3 mm wide, the diameter of this lesion would be recorded as a 21 mm DCIS (7 blocks 3 mm average block width) in our database. In many other databases, it would be a 6 mm DCIS, the largest diameter on a single section. By way of example, when the NSABP reviewed their pathologic material for the B-17 study, 75% to 90% of their cases were measured at 10 mm or less in extent (62,108). The NSABP reported tumor size as the largest diameter on a single slide. While this is clearly the simplest and most reproducible way to measure DCIS, it is often an underestimation. Compare the NSABP sizes with our cases, in which only 45% (365/806) of our conservatively treated patients had DCIS lesions measuring 10 mm or less. It is unlikely that the NSABP had twice as many smaller cases than a single group devoted to diagnosing and treating DCIS. Rather, the explanation probably lies in the way tissue was processed and the method used to estimate tumor size. In all likelihood, both groups treated tumors of similar size. Due to the difculty of estimating size, in 1997, we began evaluating the possibility of using margin width as the sole predictor of local recurrence as a surrogate for the USC/VNPI (100). The rationale was based on a multivariate analysis in which patients with margin widths less than 1 mm had a ninefold increase in the probability of local recurrence compared with patients who had 10 mm or greater margin widths. Narrow margin width was the most powerful predictor of local failure.

Figure 7.11. Probability of local recurrencefree survival by margin width for 926 breast conservation patients.

Figure 7.13. Probability of local recurrencefree survival by treatment for 308 breast conservation patients with USC/Van Nuys Prognostic Index scores of 4, 5, or 6.

Chapter 7 Ductal Carcinoma In Situ

83

Figure 7.14. Probability of local recurrencefree survival by treatment for 520 breast conservation patients with USC/Van Nuys Prognostic Index scores of 7, 8, or 9.

Figure 7.15. Probability of local recurrencefree survival by treatment for 98 breast conservation patients with modied USC/Van Nuys Prognostic Index scores of 10, 11, or 12.

In the current data set presented here, there were 325 patients with margin widths of 10 mm or greater, 19 of whom (5.8%) developed a local recurrence (2 in the radiotherapy group and 17 within the excision only group) (Fig. 7.16). The local recurrence benet for radiation therapy is signicant (p 0.05). In spite of this, the actuarial local recurrence rate at 12 years for those treated with excision alone was only 14%, virtually identical to that reported by the NSABP at 12 years for all patients treated with excision plus radiation therapy (62). There were 308 patients with USC/VNPI scores of 4, 5, or 6, of whom 8 (3%) developed a local recurrence (1 in the radiotherapy group and 7 within the excision-only group) (Fig. 7.13). The USC/VNPI is a better predictor of local recurrence than margin width alone (half as many recurrences), and it should be, since it is based on ve predictive factors, including margin width. Nevertheless, there are so few recurrences among patients with widely clear margins that for all practical purposes, margin width can be used by itself as a surrogate for the USC/VNPI. Figures 7.17 to 7.20 evaluate local recurrence by various parameters for patients with 10 mm or greater margin widths. Figure 7.17 shows that if widely clear margins are obtained, the presence of comedonecrosis does not signicantly increase the local recurrence rate. Figure 7.18 shows that if widely clear margins are obtained, high nuclear grade (grade 3) does not signicantly increase the local recurrence rate. Figure 7.19 shows that if widely clear margins are obtained, young age does not signicantly increase the local recurrence rate. Figure 7.20 shows that if widely clear margins are obtained, large size does not increase the local recurrence rate, although there are too few lesions greater than 40 mm with 10 mm or greater margins (n 17) to draw rm conclusions.

TREATMENT OF THE AXILLA FOR PATIENTS WITH DUCTAL CARCINOMA IN SITU


In 1986, our group suggested that axillary lymph node dissection be abandoned for DCIS (109). In 1987, the NSABP made axillary node dissection for patients with DCIS optional at the discretion of the surgeon. Since that time, we have published a series of papers that continue to show that axillary node dissection is not indicated for patients with DCIS (99,110). Our group has performed a total of 673 node evaluations, 3 of which (0.4%) contained positive nodes by hematoxylin and eosin (H&E) staining. Two of those patients, both with macromets, were treated with adjuvant chemotherapy. Both were alive and well without local or distant recurrence at 8 and 10 years after their initial surgery, respectively (both had mastectomies, and invasive cancer was likely missed during the serial sectioning of their specimens). The third patient had a cluster of 40 cells discovered by immunohistochemical staining that were then retrospectively seen on H&E. This patient was not increased in stage and was not treated with chemotherapy. Frykberg et al., in their review of the management of DCIS, compiled the data of nine studies with a total of 754 patients. The incidence of axillary lymph node metastasis for patients with DCIS was 1.7% (111). SENTINEL NODE BIOPSY FOR DUCTAL CARCINOMA IN SITU Through 2008, I had performed 281 sentinel node biopsies for patients with DCIS. Twelve (5%) were positive by immunohistochemistry (IHC) only, 1 was positive by IHC and H&E (40 cells), and the rest (268) were negative by both IHC and H&E.

TABLE 7.2
USC/VNPI Score
4, 5, or 6 7, 8, or 9 10, 11, or 12

Treatment Guidelines, University of Southern California/Van Nuys Prognostic Index (USC/VNPI)


Recommended Treatment
Excision only Excision plus radiation Mastectomy

84

Section I Oncology and Oncoplastic Surgery

Figure 7.16. Probability of local recurrencefree survival by treatment for 325 breast conservation patients with margins widths 10 mm.
In every case there were only a few positive cells (range 4 to 93). In no case were any patients upstaged to stage II nor were any treated with chemotherapy. All are alive and well without distant recurrence, with follow-up ranging from 0.7 to 10.4 years (average 4.4 years). Not all IHC-positive cells are cancer cells. Some may merely be cytokeratin-positive debris. Their morphology must be closely evaluated. My policy for sentinel node biopsy in patients with DCIS is as follows. I perform it for all patients with DCIS who are undergoing a mastectomy. I perform it if the DCIS is an upper outer quadrant lesion and the sentinel node can be easily removed through the same incision. I also remove a sentinel node if the DCIS is palpable or greater than 4 cm on mammography and/or MRI or there is questionable microinvasion.

Figure 7.18. Probability of local recurrencefree survival by nuclear grade for 325 breast conservation patients with margins widths 10 mm.
breast function. The oncoplastic surgeon must be constantly thinking, How can I remove this cancer with large margins of normal tissue while at the same time make the patient look as good as or better than she looks now? While oncoplastic surgery is used for patients with both invasive and noninvasive breast cancer, it is particularly important for patients with DCIS. Now that excision without radiation therapy is a nationally accepted method of treatment for patients with DCIS (92), widely clear margins are of even greater importance than previously appreciated. The goals of oncoplastic breast conservation surgery include the following: 1. 2. 3. 4. Complete removal of the lesion. Clear margins: the larger the better. Good to excellent cosmetic result. Going to the operating room one time to perform the denitive procedure.

ONCOPLASTIC BREAST SURGERY


Oncoplastic breast conservation surgery combines oncologic principles with plastic surgical techniques. However, it is much more than a combination of two disciplines. It is a philosophy that requires vision, passion, a knowledge of anatomy, and an appreciation and understanding of aesthetics, symmetry, and

ONCOPLASTIC RESECTION
When treating a patient with biopsy-proven breast cancer, surgeons have generally made a small, cosmetically placed curvilinear incision over the area to be removed (Fig. 7.21). They

Figure 7.17. Probability of local recurrencefree survival by the


presence or absence of comedonecrosis for 325 breast conservation patients with margins widths 10 mm.

Figure 7.19. Probability of local recurrencefree survival by age for 325 breast conservation patients with margins widths 10 mm.

Chapter 7 Ductal Carcinoma In Situ

85

Figure 7.20. Probability of local recurrencefree survival by tumor size for 325 breast conservation patients with margins widths 10 mm.

excised no skin, took a relatively small piece of breast tissue, accepted nontransection as the denition of clear margins, did not require complete and sequential tissue processing, and used radiation therapy routinely. The trend is changing. During the last 25 years, my colleagues and I have developed a comprehensive multidisciplinary oncoplastic approach for the excision of breast cancer (12,112,113). It requires surgical coordination with a pathologist, a radiologist, and, on occasion, a plastic surgeon. Oncoplastic surgery combines sound surgical oncologic principles with plastic surgical techniques. Coordination of the two surgical disciplines may help to avoid poor cosmetic results after wide excision and may increase the number of women who can be treated with breast-conserving surgery by allowing larger breast excisions with more acceptable cosmetic results. These techniques are applicable to patients with both noninvasive (DCIS) and invasive breast cancer. Oncoplastic resection is a therapeutic procedure, not a breast biopsy. It is performed on patients with a proven diagnosis of breast cancer. This approach was strongly supported by the 2005 Consensus Conference on Image-Detected Breast Cancer (58).

An important goal in caring for a woman with breast cancer is to go to the operating room a single time and to perform a denitive procedure that does not require reoperation. Whenever possible, the initial breast biopsy should be made using a minimally invasive percutaneous technique (58). This usually provides ample tissue for diagnosis and should be possible in more than 95% of currently diagnosed cases. When excising breast cancer, the surgeon faces two opposing goals: clear margins versus an acceptable cosmetic result. From an oncologic point of view, the largest specimen possible should be removed in an attempt to achieve the widest possible margins. From a cosmetic point of view, a much smaller amount of tissue should be removed in order to achieve the best possible cosmetic result. The surgeon must tread a ne line as he or she tries to satisfy two masters. The rst attempt to remove a cancerous lesion is critical. The rst excision offers the best chance to remove the entire lesion in one piece, evaluate its extent and margin status, and achieve the best possible cosmetic result. Currently, as many as 40% to 50% of new breast cancer cases are discovered by modern state-of-the-art imaging (mostly mammography). Intraoperatively, they are grossly both nonpalpable and nonvisualizable. Under these circumstances, the surgeon essentially operates blindly. Multiple hooked wires can help dene the extent of the lesion radiographically (Fig. 7.22). Using bracketing wires, the surgeon should make an attempt to excise the entire lesion within a single piece of tissue. This often will include overlying skin as well as pectoral fascia (Fig. 7.23). The tissue should be precisely oriented for the pathologist. If the specimen is removed in multiple pieces rather than a single piece, there is little likelihood of evaluating margins and size accurately. Figure 7.24 shows an excision specimen with four additional pieces that represent the new margins. The additional pieces are too small and do not reect the true margins of the original specimen. If one makes a judgment on margin clearance based on these small additional pieces, that judgment might very well be incorrect.

Figure 7.21. A patient with biopsy-proven breast cancer in the


upper outer quadrant of the right breast. The cancer has been excised through a small, cosmetically placed curvilinear incision over the lesion. No skin has been removed. Until now, this has been the standard way of excising breast cancer.

Figure 7.22. Specimen radiograph of a patient with four bracketing wires. Two wires to the right bracket a stellate lesion. The two wires to the left bracket microcalcications that extend from the stellate lesion.

86

Section I Oncology and Oncoplastic Surgery

Preoperative planning requires discussion between, at a minimum, the oncoplastic surgeon and the radiologist. Often, a plastic surgeon, medical oncologist, radiation oncologist, and others may be included. All of the preoperative tests must be evaluated and integrated along with information about the pathologic subtype, size, and extent of the lesion. Is it an invasive lobular cancer that might be larger than expected? Is there a signicant DCIS component? Does this patient want symmetry? If yes, should it be done during the same operative procedure or as a delayed procedure? And so on.

ONCOPLASTIC EXCISIONS
There are numerous oncoplastic incisions. They include but are not limited to the following: 1. Upper pole a. Crescent b. Batwing c. Hemibatwing 2. Lower pole a. Triangle b. Trapezoid c. Reduction d. Inframammary (hidden scar; does not remove skin) 3. Any segment of the breast a. Radial: ellipse (most versatile) b. Circumareola with advancement ap (does not remove skin) c. Donut mastopexy. Some of these excisions are illustrated in the following, using selected cases. RADIAL ELLIPSE Figure 7.25 shows the preoperative markings for a patient with a lesion in the 9:00 position of the right breast. Three 0.1-cc wheals of isosulfan blue dye were injected intradermally for sentinel node mapping (intradermal injections should not

Figure 7.23. Specimen from a hemibatwing excision. Skin, full


thickness of breast, and pectoral fascia has been removed. Four wires bracket the extent of the lesion.

ONCOPLASTIC STEPS
There are several important steps to a proper oncoplastic operation. 1. Make sure that reoperative planning includes the following: a. Mammography (preferably digital) b. Breast ultrasound (at a minimum, the involved quadrant, but preferably both breasts) c. Axillary ultrasound and needle biopsy of suspicious nodes d. Breast MRI e. An evaluation of the size of the cancer versus the size of the breast f. Detailed family history and genetic counseling, if appropriate g. Integration of patient wishes into the operative plan 2. Excise the lesion in one piece (often includes skin, breast segment, and pectoral fascia) 3. Reshape the ipsilateral breast 4. Ensure symmetry for the contralateral breast

Figure 7.24. An excision specimen with four additional pieces of


tissue that allegedly represent the new margins. The additional pieces are too small and do not reect the true margins of the original specimen. If one makes a judgment on margin clearance based on these small additional pieces, that judgment might very well be wrong.

Figure 7.25. Preoperative markings for a patient with a lesion in the 9:00 position of the right breast. Three 0.1-cc wheals of isosulfan blue dye have been injected intradermally for sentinel node localization. The sentinel node incision has been marked.

Chapter 7 Ductal Carcinoma In Situ

87

Figure 7.26. The entire lateral segment down to and including


the pectoralis major fascia has been removed and the surrounding tissue undermined. Clips are used to mark the superior, inferior, medial, lateral, and deep margins of the excision. A sentinel node biopsy has been performed.

Figure 7.28. The result of a radial ellipse in the upper inner quadrant of the left breast. The skin has been closed with a subcuticular suture and Dermabond (Ethicon, Inc., Cincinnati, OH). The patient is 4 days postoperative.

be used unless skin is going to be removed; it will tattoo the skin). The entire lateral segment down to and including the pectoralis major fascia was removed and the surrounding tissue undermined (Fig. 7.26). A sentinel node biopsy was performed. The remaining tissue was then advanced with deep sutures (Fig. 7.27) and the breast remodeled (Fig. 7.28). Figures 7.29 and 7.30 show the cosmetic results of radial elliptical excisions. I drain all segmental resections for 24 to 48 hours. All wounds are completely closed in layers. The cosmetic result should be constantly monitored and reevaluated during wound closure. Often, the head of the operating table will need to be elevated during closure to evaluate the cosmetic result and symmetry. Because all wounds are completely closed in layers and all dead spaces obliterated, these patients are not good candidates for postoperative balloon radiation therapy. For the oncoplastic cases performed as illustrated here, I prefer standard external beam radiation therapy or intraoperative radiation therapy. A radial segmental resection may alter the size and shape of the breast, but good cosmetic results are generally achieved

Figure 7.29. The result of a radial ellipse in the lower inner quadrant of the left breast. The patient is 2 years postoperative.

Figure 7.27. The segment has been removed. The surrounding


breast tissue has been undermined for a distance of 56 cm in all directions and is now being advanced with deep sutures.

Figure 7.30. The result of radial a radial ellipse in the upper inner quadrant of the right breast. The patient is 2 years postoperative.

88

Section I Oncology and Oncoplastic Surgery

Figure 7.31. A 65-year-old woman presented with needle


biopsyproven DCIS in the right breast. The DCIS was central with a bloody nipple discharge. A wide local excision, including the nippleareola complex, using two guide wires and a reduction pattern was used.

Figure 7.33. The lower central segment of the right breast has been removed, the incisions along the inframammary sulcus have been lengthened, and the remaining breast has been undermined from the chest wall.

(Figs. 7.28 to 7.30). A radial excision usually will not displace the nipple-areola complex even though overlying skin is removed. If it does, the nipple can be recentralized by excising a crescent-shaped piece of skin (see crescent excision below). In contrast to the old axiom the seroma is your friend, when doing oncoplastic breast surgery the exact opposite is true. It is best if the wound heals with as little seroma and blood as possible. Regardless of how the wound is closed, there will always be a small amount of uid in the biopsy cavity, but this should be minimized. SEGMENTECTOMY USING A VARIETY OF REDUCTION MAMMOPLASTY EXCISIONS In a fully counseled woman with a larger breast who might benet from a reduction mammoplasty or a mastopexy, a variety of creative reduction/mastopexy excisions can be designed that allow for complete removal of the lesion. For lesions in the lower hemisphere of the breast a standard reduction incision can be used. This allows access to lesions

from 2:00 to 10:00, going clockwise. Large amounts of breast tissue can be removed with excellent cosmetic results and generally widely clear margins. A 65-year-old woman presented with needle biopsyproven DCIS in the right breast. The DCIS was central with a bloody nipple discharge. It was elected to do a wide local excision, including the nipple-areola complex, using two guide wires and a reduction pattern (Fig. 7.31). Figures 7.32 to 7.35 show the details of the procedure and early results. TRIANGLE The triangle excision removes a triangle-shaped piece of tissue from the lower hemisphere of the breast (generally from the 5:00, 6:00, or 7:00 position). It does not elevate the nipple-areola complex. This procedure is ideal for a lower hemisphere lesion in a patient who

Figure 7.34. The remaining tissue has been reapproximated and Figure 7.32. The excised lower central segment, including the
nipple-areola complex, of the right breast. will be closed with deep sutures. A sentinel node biopsy has been done through a separate incision, but it could have been done through the reduction incision by extending the undermining to the lower axilla.

Chapter 7 Ductal Carcinoma In Situ

89

Figure 7.35. The patient is 2 weeks postoperative. The lower central segment of the right breast, including the nipple-areola complex, has been removed through a reduction incision, and the left breast has been reduced to match the right. The right nipple areola complex will be created about 3 months postoperatively.

Figure 7.37. The lesion was removed through a curvilinear incision in the 5:30 position (marked in black ink), but the superior margin was positive. Magnetic resonance imaging revealed residual disease on the left breast extending toward the nipple. A triangleshaped excision has been drawn on the breast to allow reexcision of the entire segment from inframammary sulcus to the nipple.

does not want the nipple-areola complex elevated as it would be with a standard reduction. Figure 7.36 shows a 48-year-old patient with an invasive lesion in the 5:30 position on the left breast. It was initially removed at another facility through a curvilinear incision, but the superior margin was positive. An MRI revealed residual disease in the left breast extending toward the nipple. Figures 7.37 to 7.40 show the details of the procedure and nal result. INFRAMAMMARY APPROACH (HIDDEN SCAR) The inframammary approach places the incision in the inframammary sulcus and is generally invisible with the patient in the upright position. This incision is an excellent choice for lesions in the posterior inferior portion of the breast. It does not remove any skin. In a larger breast, lesions in the upper hemisphere can easily be reached. Figures 7.41 to 7.47 detail a 51-year-old patient with a 1-cm lesion in the posterior lateral breast in whom the lesion was widely excised using an inframammary approach.

Figure 7.38. The segment has been excised, the remaining breast tissue widely undermined, the margins clipped, the inframammary sulcus opened, and a drain placed.

Figure 7.36. A 48-year-old patient with an invasive lesion in the


5:30 position of the left breast.

Figure 7.39. The wound has been closed. This is an intraoperative


picture.

90

Section I Oncology and Oncoplastic Surgery

Figure 7.40. The patient is 1-week posttriangle excision on the


left breast. There is mild postoperative swelling on the left.

Figure 7.43. The patient ready for surgery. Two guide wires are in place marking the lesion. Ultrasound has been used intraoperatively to map out the exact position of the lesion (pink stellate cartoon), and a curvilinear black line has been drawn in natural skin lines to show how most surgeons would approach this lesion.

Figure 7.41. A 51-year-old patient with a 1-cm lesion in the posterior lateral left breast.

Figure 7.44. Rather than a curvilinear incision over the lesion, the approach will be using an inframammary incision with ultrasound assistance throughout the procedure.

Figure 7.42. Mediolateral and craniocaudal mammograms show


the lesion about nipple high and lateral in the left breast. Triangles mark the lesion in each view.

Figure 7.45. The posterior portion of the breast is being excised with both guide wires in place.

Chapter 7 Ductal Carcinoma In Situ

91

Figure 7.46. The patient is 18 months postinframammary excision followed by radiation therapy. The incision is invisible unless the breast is pulled superiorly.

Figure 7.48. A 55-year-old patient with a right breast inltrating ductal carcinoma previously excised using a circumareolar incision. The superior margin was positive. She was reexcised using a crescent excision on the right and a contralateral left crescent mastopexy for symmetry.

CRESCENT, BATWING, AND HEMIBATWING For lesions in the upper hemisphere (8:00 to 4:00 going clockwise), crescent, batwing or hemibatwing excisions can be used. These incisions allow the lesion to be generously removed (specimens are often 100 g or more) while allowing recontouring the breast in a desirable fashion. All lift the nipple-areola complex. A contralateral crescent can be done simultaneously for symmetry. Figure 7.48 shows a woman whose lesion in the 12:00 position of the right breast was excised using a crescent mastopexy incision. A contralateral left crescent mastopexy was done for symmetry. Figure 7.49 shows the patient 4 months postoperative. Figure 7.50 shows a patient with a cancer in the 3:00 position of the left breast. It is going to be removed using a hemibatwing on the left with a crescent mastopexy on the right for symmetry. The hemibatwing is a combination of a radial ellipse and a crescent excision. It is designed to raise the nipple-areola complex while excising a radial segment of the breast. Figure 7.51 show the patient 6 weeks postoperative.

Figure 7.49. The patient in Figure 48 at 4 months postoperative. Excellent symmetry has been achieved, and the cancer has been removed with widely clear margins. She will receive radiation therapy at the conclusion of chemotherapy.

Figure 7.47. The breast has been pulled superiorly and the incision is barely visible as a ne white line.

Figure 7.50. The patient has an invasive carcinoma in the 3:00 position of the left breast. The plans have been drawn for a left hemibatwing and a right crescent mastopexy.

92

Section I Oncology and Oncoplastic Surgery

Figure 7.51. The patient in Figure 7.50 at 6 weeks postoperative.


The breasts are more rounded, and the cosmetic result will be excellent. The left breast cancer was excised with widely clear margins.

Figure 7.53. The patient in Figure 7.52 at 1 day postoperative.


Figures 7.52 and 7.53 show a patient with bilateral DCIS who was excised using bilateral hemibatwing excisions. Widely clear margins were obtained on both sides. I commonly use a combination of hemibatwing on the side of the cancer with a crescent mastopexy on the contralateral side for symmetry. The crescent should be no taller than 3 cm or it will elongate the areola. If the nipple-areola complex needs to be elevated more than 3 cm, a more formal reduction technique should be used. THE CONTRALATERAL BREAST When symmetry is desired, the contralateral breast will generally need to be adjusted. This can be done during the same operative procedure as the initial cancer or as a delayed procedure. The advantage of doing both sides simultaneously is in having a single operative procedure. The disadvantage is that the final pathology and, in particular, the margin status, is unknown before altering the appearance of the opposite breast. However, if the patient decides that she is willing to accept the risks of close or positive margins (that might require reoperation) and would prefer a single operation (and most do), the contralateral side can be adjusted at the same operation.

If permanent microscopic sections reveal involved margins and the residual breast is amenable to reexcision, the inammatory response and induration should be allowed to subside if the reexcision is for DCIS. If the reexcision is for invasive cancer, it can be done immediately or after the completion of chemotherapy (if indicated) but prior to radiation therapy. The cosmetic results from reexcision are often better after a sufcient period of wound healing and scar resolution.

SUMMARY
DCIS is now relatively common, and its frequency is increasing. Most of this is due to better and more frequent mammography for a greater proportion of the female population. Not all microscopic DCIS will progress to clinical cancer, but if a patient has DCIS and is not treated, she is more likely to develop an ipsilateral invasive breast cancer than is a woman without DCIS. The comedo subtype of DCIS is more aggressive and malignant in its histologic appearance and is more likely to be associated with subsequent invasive cancer than the noncomedo subtypes. Comedo DCIS is more likely to have a high S phase, overexpress HER2/neu, and show increased thymidine labeling as compared with noncomedo DCIS. Comedo DCIS treated conservatively is also more likely to recur locally than noncomedo DCIS. However, separation of DCIS into two groups by architecture is an oversimplication and does not reect the biologic potential of the lesion as well as stratication by nuclear grade and comedo-type necrosis. Most DCIS detected today will be nonpalpable. They will be detected by mammographic calcications. It is not uncommon for DCIS to be larger than expected by mammography, to involve more than a quadrant of the breast, and to be unicentric in its distribution. Preoperative evaluation should include mammography (preferably digital) with compression magnication and ultrasonography. MRI is becoming increasingly more popular, and I obtain it on every patient diagnosed with any form of breast cancer. The surgeon and the radiologist should plan the excision procedure carefully, including the number of wires and their approach. The rst attempt at excision is the best chance to get a complete excision with a good cosmetic result.

Figure 7.52. This patient has bilateral ductal carcinoma in situ


(upper outer quadrant on the right and upper inner quadrant on the left). She will be excised using bilateral hemibatwing excisions.

Chapter 7 Ductal Carcinoma In Situ

93

Reexcisions often yield poor cosmetic results, and the overall plan should be to avoid them whenever possible. The initial breast biopsy should be an image-guided needle biopsy. After establishment of the diagnosis, the patient should be counseled. If she is motivated for breast conservation, the surgeon and radiologist should plan the procedure carefully, using multiple wires to map out the extent of the lesion. When considering the entire population of patients with DCIS without subset analyses, the prospective randomized trials have shown that postexcisional radiation therapy can reduce the relative risk of local recurrence by about 50% for conservatively treated patients. In some low-risk DCIS patients, however, the costs may outweigh the potential benets. In spite of a relative 50% reduction in the probability of local recurrence, the absolute reduction may be only a few percent. While local recurrence is extremely important, breast cancerspecic survival is the most important endpoint for all patients with breast cancer, including patients with DCIS, and no DCIS trial has ever shown a survival benet for radiation therapy when compared with excision alone. Moreover, radiation therapy is not without nancial and physical cost. Because of this, in recent years, an increasing number of selected patients with DCIS have been treated with excision alone. Excision alone has now become an acceptable form of treatment for selected patients in the 2008 NCCN guidelines. The USC/VNPI uses ve independent predictors to predict the probability of local recurrence after conservative treatment for DCIS. These include tumor size, margin width, nuclear grade, age, and the presence or absence of comedonecrosis. In combination, they can be used as an aid to identify subgroups of patients with extremely low probabilities of local recurrence after excision alone, for example, patients who score 4, 5, or 6 using the USC/VNPI. If size cannot be accurately determined, margin width by itself can be used as a surrogate for the USC/VNPI, although it is not quite as good. Oncoplastic surgery combines sound surgical oncologic principles with plastic surgical techniques. Coordination of the two surgical disciplines may help to avoid poor cosmetic results after wide excision and may increase the number of women who can be treated with breast-conserving surgery by allowing larger breast excisions with more acceptable cosmetic results. Oncoplastic surgery requires cooperation and coordination of surgical oncology, radiology, and pathology. Oncoplastic resection is a therapeutic procedure, not a breast biopsy, and it is performed on patients with a proven diagnosis of breast cancer. New oncoplastic techniques that allow for more extensive excisions can be used to achieve both acceptable cosmesis and widely clear margins, reducing the need for radiation therapy in many cases of DCIS. The decision to use excision alone as treatment for DCIS should only be made if complete and sequential tissue processing has been used and the patient has been fully informed and has participated in the treatment decision-making process.

DCIS that will not, the treatment selection process will become much simpler.

EDITORIAL COMMENTS This discussion of DCIS represents a comprehensive summary by a participant in one of the most active groups investigating the disease. The VNPI provides one of the rst reasonably reliable means of staging the disease and helping management programs. The criteria developed for prognosticationincluding tumor size, margins, and histologic gradehave been proven in multiple studies to be of signicance. What DCIS uniquely provides, however, is an in vivo laboratory for understanding breast cancer progression. What is critically needed are means of exploiting the modern technologies of molecular biology to more critically assess the genetic bases for disease progression. Obviously, there are DCIS lesions that can be left in situ with almost no potential for malignant progression, whereas others will rapidly result in invasive breast cancer. We simply cannot tell them apart at this time. Although it can be argued that disease progression simply reects a stochastic process in which additional random genetic hits result in malignancy in an unpredictable fashion, it may well be that certain patterns of gene expression predispose DCIS lesions to progression. The technologies of gene array analysis, in which the ability to analyze virtually every expressed gene in a cancer can be combined with laserassisted microdissection and can permit a direct comparison of early invasive lesions with directly juxtaposed noninvasive lesions, will provide enlightening answers to these questions in the near future. Furthermore, it is hoped that this will also lead to molecular evaluation of margins rather than the morphologic criteria on which all clinicians must now rely. M.E.L.

REFERENCES
1. Jemal A, Siegel R, Ward E, et al. Cancer statistics, 2008. CA Cancer J Clin 2008;58(2):7196. 2. Burstein HJ, Polyak K, Wong JS, et al. Ductal carcinoma in situ of the breast. N Engl J Med 2004;350(14):14301441. 3. Seth A, Kitching R, Landberg G, et al. Gene expression proling of ductal carcinomas in situ and invasive breast tumors. Anticancer Res 2003;23:20432051. 4. Porter D, Lahti-Domenici J, Keshaviah A, et al. Molecular markers in ductal carcinoma in situ of the breast. Mol Cancer Res 2003;1:362375. 5. Ma XJ, Salunga R, Tuggle JT, et al. Gene expression proles of human breast cancer progression. Proc Natl Acad Sci U S A 2003;100:59745979. 6. Page D, Anderson T. Diagnostic Histopathology of the Breast. New York: Churchill Livingstone; 1987:157174. 7. Patchefsky A, Schwartz G, Finkelstein S, et al. Heterogeneity of intraductal carcinoma of the breast. Cancer 1989;63:731741. 8. Nemoto T, Vana J, Bedwani R, et al. Management and survival of female breast cancer: results of a national survey by the American College of Surgeons. Cancer 1980;45:29172924. 9. Ashikari R, Hadju S, Robbins G. Intraductal carcinoma of the breast. Cancer 1971;28: 11821187. 10. Silverstein MJ. Ductal carcinoma in situ of the breast. Ann Rev Med 2000;51:1732. 11. Baxter N, Virnig B, Durham S, et al. Trends in the treatment of ductal carcinoma in situ of the breast. J Natl Cancer Inst 2004;96:443448. 12. Silverstein MJ. The Van Nuys Breast Center: the rst free-standing multidisciplinary breast center. Surg Oncol Clinics N Am 2000;9(2):159175. 13. Veronesi U, Saccozzi R, Del Vecchio M, et al. Comparing radical mastectomy with quadrantectomy, axillary dissection and radiotherapy in patients with small cancers of the breast. N Engl J Med 1981;305:610. 14. Van Dongen J, Bartelink H, Fentiman I, et al. Randomized clinical trial to assess the value of breast-conserving therapy in stage I and II breast cancer, EORTC 10801 trial. Monogr Natl Cancer Inst 1992;11:1518.

THE FUTURE
Our knowledge of DCIS genetics and molecular biology is increasing at a remarkably rapid rate. Future studies are likely to identify molecular markers that will allow us to differentiate DCIS with an aggressive potential from DCIS that is merely a microscopic nding. Once we can distinguish DCIS that will soon develop the potential to invade and metastasize from

94

Section I Oncology and Oncoplastic Surgery


51. Tabar L, Smith RA, Vitak B, et al. Mammographic screening: a key factor in the control of breast cancer. Cancer J 2003;9(1):1527. 52. Fisher E, Sass R, Fisher B, et al. Pathologic ndings from the National Surgical Adjuvant Breast Project (protocol 6) I. Intraductal carcinoma (DCIS). Cancer 1986;57:197208. 53. Simpson T, Thirlby R, Dail D. Surgical treatment of ductal carcinoma in situ of the breast: 10 to 20 year follow-up. Arch Surg 1992;127:468472. 54. Holland R, Hendriks J, Verbeek A, et al. Extent, distribution, and mammographic/ histological correlations of breast ductal carcinoma in situ. Lancet 1990;335:519522. 55. Holland R, Faverly D. Whole organ studies. In: Silverstein MJ, Recht A, Lagios M, eds. Ductal Carcinoma in Situ of the Breast. Philadelphia: Lippincott, Williams and Wilkins; 1997:233240. 56. Noguchi S, Aihara T, Koyama H, et al. Discrimination between multicentric and multifocal carcinomas of breast through clonal analysis. Cancer 1994;74:872877. 57. Tabar L, Dean P. Basic principles of mammographic diagnosis. Diagn Imag Clin Med 1985;54:146157. 58. Silverstein M, Lagios M, Recht A, et al. Image-detected breast cancer: state of the art diagnosis and treatment. J Am Coll Surg 2005;201:586597. 59. Silverstein M. Wheres the outrage. J Am Coll Surg 2009;208:7879. 60. Silverstein MJ Intraductal breast carcinoma: two decades of progress? Am J Clin Oncol 1991;14(6):534537. 61. Silverstein MJ Noninvasive breast cancer: the dilemma of the 1990s. Obstet Gynecol Clin North Am 1994;21(4):639658. 62. Fisher B, Land S, Mamounas E, et al. Prevention of invasive breast cancer in women with ductal carcinoma in situ: an update of the National Surgical Adjuvant Breast and Bowel Project Experience. Semin Oncol 2001;28(4):400418. 63. Fentiman I, Fagg N, Millis R, et al. In situ ductal carcinoma of the breast: implications of disease pattern and treatment. Eur J Surg Oncol 1986;12:261266. 64. Solin L, Kurtz J, Fourquet A, et al. Fifteen year results of breast conserving surgery and denitive breast irradiation for treatment of ductal carcinoma in situ of the breast. J Clin Oncol 1996;14:754763. 65. UK Coordinating Committee on Cancer Research (UKCCCR), Ductal Carcinoma in Situ (DCIS) Working Party. Radiotherapy and tamoxifen in women with completely excised ductal carcinoma in situ of the breast in the UK, Australia, and New Zealand: randomised controlled trial. Lancet 2003;362:95102. 66. Viani GA, Stefano EJ, Afonso SL, et al. Breast-conserving surgery with or without radiotherapy in women with ductal carcinoma in situ: a meta-analysis of randomized trials. Radiation Oncol 2007;2:2839. 67. Emdin SO, Granstrand B, Ringberg A, et al. SweDCIS: radiotherapy after sector resection for ductal carcinoma in situ of the breast. Results of a randomised trial in a population offered mammographic screening. Acta Oncol 2006;45:536543. 68. Fisher B, Jeong J, Anderson S, et al. Twenty-ve year follow-up of a randomized trial comparing radical mastectomy, total mastectomy, and total mastectomy followed by irradiation. N Engl J Med 2002;347:567575. 69. Group, EBCTC. Effects of radiotherapy and differences in the extent of surgery for early breast cancer on local recurrence and on 15-year survival. Lancet 2005;366:20872106. 70. Silverstein MJ, Lagios M, Martino S, et al. Outcome after local recurrence in patients with ductal carcinoma in situ of the breast. J Clin Oncol 1998;16:13671373. 71. Romero L, Klein L, Ye W, et al. Outcome after invasive recurrence in patients with ductal carcinoma in situ of the breast. Am J Surg 2004;188:371376. 72. Swain S. Ductal carcinoma in situincidence, presentation and guidelines to treatment. Oncology 1989;3:2542. 73. Fisher B, Costantino J, Redmond C, et al. Lumpectomy compared with lumpectomy and radiation therapy for the treatment of intraductal breast cancer. N Engl J Med 1993;328: 15811586. 74. Fisher B, Dignam J, Wolmark N, et al. Tamoxifen in treatment of intraductal breast cancer: National Surgical Adjuvant Breast and Bowel Project B-24 randomized controlled trial. Lancet 1999;353:19932000. 75. Fisher B, Dignam J, Wolmark N, et al. Lumpectomy and radiation therapy for the treatment of intraductal breast cancer: ndings from National Surgical Adjuvant Breast and Bowel Project B-17. J Clin Oncol 1998;16(2):441452. 76. Julien J, Bijker N, Fentiman I, et al. Radiotherapy in breast conserving treatment for ductal carcinoma in situ: rst results of EORTC randomized phase III trial 10853. Lancet 2000;355:528533. 77. Page D, Dupont W, Rogers L, et al. Continued local recurrence of carcinoma 1525 years after a diagnosis of low grade ductal carcinoma in situ of the breast treated only by biopsy. Cancer 1995;76:11971200. 78. Zafrani B, Leroyer A, Fourquet A, et al. Mammographically detected ductal in situ carcinoma of the breast analyzed with a new classication. A study of 127 cases: correlation with estrogen and progesterone receptors, p53 and c-erbB-2 proteins, and proliferative activity. Semin Diagn Pathol 1994;11(3):208214. 79. Schwartz G. The role of excision and surveillance alone in subclinical DCIS of the breast. Oncology 1994;8(2):2126. 80. Schwartz G. Treatment of subclinical ductal carcinoma in situ of the breast by local excision and surveillance: an updated personal experience. In: Silverstein MJ, Recht A, Lagios M, eds. Ductal Carcinoma in Situ of the Breast. Philadelphia: Lippincott, Williams and Wilkins; 2002:308321. 81. Holland R, Faverly D. Whole organ studies. In: Silverstein M, ed. Ductal Carcinoma in Situ of the Breast. Baltimore, MD: Williams and Wilkins; 1997:233240. 82. Holland R, Hendriks J. Microcalcications associated with ductal carcinoma in situ: mammographic-pathologic correlation. Semin Diagn Pathol 1994;11(3):181192. 83. Page D, Dupont W, Roger L, et al. Atypical hyperplastic lesions of the female breast. A long-term follow-up study. Cancer 1985;55:26982708. 84. Lagios M. Controversies in diagnosis, biology, and treatment. Breast J 1995;1:6878. 85. Group, EBCTC. Favorable and unfavorable effects on long-term survival of radiotherapy for early breast cancer: an overview of the randomized trials. Lancet 2006;2000:17571770.

15. Veronesi U, Ban A, Salvadori B, et al. Breast conservation is the treatment of choice in small breast cancer: long-term results of a randomized trial. Eur J Cancer 1990;26:668670. 16. Fisher B, Redmond C, Poisson R, et al. Eight-year results of a randomized clinical trial comparing total mastectomy and lumpectomy with or without radiation therapy in the treatment of breast cancer. N Eng J Med 1989;320:822828. 17. Veronesi U, Cascinelli N, Mariani L, et al. Twenty-year follow-up of a randomized study comparing breast-conserving surgery with radical mastectomy for early breast cancer. N Engl J Med 2002;347:12271232. 18. Fisher B, Anderson S, Bryant J, et al., Twenty-year follow-up of a randomized trial comparing total mastectomy, lumpectomy, and lumpectomy plus irradiation for the treatment of invasive breast cancer. N Engl J Med 2002;347:12331241. 19. Lagios MD. Duct carcinoma in situ: pathology and treatment. Surg Clin North Am 1990; 70:853871. 20. Tavassoli F. Intraductal carcinoma. In: Tavassoli FA, ed. Pathology of the Breast. Norwalk, CT: Appleton and Lange; 1992:229261. 21. Aasmundstad T, Haugen O. DNA Ploidy in intraductal breast carcinomas. Eur J Cancer 1992;26:956959. 22. Meyer J. Cell kinetics in selection and stratication of patients for adjuvant therapy of breast carcinoma. NCI Monogr 1986;1:2528. 23. Allred D, Clark G, Molina R, et al. Overexpression of HER-2/neu and its relationship with other prognostic factors change during the progression of in situ to invasive breast cancer. Hum Pathol 1992;23:974979. 24. Barnes D, Meyer J, Gonzalez J, et al. Relationship between c-erbB-2 immunoreactivity and thymidine labelling index in breast carcinoma in situ. Breast Cancer Res Treat 1991;18:1117. 25. Bartkova J, Barnes D, Millis R, et al. Immunhistochemical demonstration of c-erbB-2 protein in mammary ductal carcinoma in situ. Hum Pathol 1990;21(11):11641167. 26. Liu E, Thor A, He M, et al. The HER2 (c-erbB-2) oncogene is frequently amplied in in situ carcinomas of the breast. Oncogene 1992;7:10271032. 27. van de Vijver M, Peterse J, Mooi WJ, et al. Neu-protein overexpression in breast cancer: association with comedo-type ductal carcinoma in situ and limited prognostic value in stage II breast cancer. N Engl J Med 1988;319:12391245. 28. Lagios M, Margolin F, Westdahl P, et al. Mammographically detected duct carcinoma in situ. Frequency of local recurrence following tylectomy and prognostic effect of nuclear grade on local recurrence. Cancer 1989;63:619624. 29. Schwartz G, Finkel G, Carcia J, et al. Subclinical ductal carcinoma in situ of the breast: treatment by local excision and surveillance alone. Cancer 1992;70:24682474. 30. Silverstein MJ, Waisman J, Gierson E, et al. Radiation therapy for intraductal carcinoma: Is it an equal alternative? Arch Surg 1991;126:424428. 31. Solin L, Yeh I, Kurtz J, et al. Ductal carcinoma in situ (intraductal carcinoma) of the breast treated with breast-conserving surgery and denitive irradiation. Correlation of pathologic parameters with outcome of treatment. Cancer 1993;71:25322542. 32. Silverstein MJ, Barth A, Waisman J, et al., Predicting local recurrence in patients with intraductal breast carcinoma (DCIS). Proc Am Soc Clin Oncol 1995;14:117. 33. Silverstein MJ, Poller D, Craig P, et al. A prognostic index for ductal carcinoma in situ of the breast. Cancer 1996;77:22672274. 34. Lagios M, Westdahl P, Margolin F, et al. Duct carcinoma in situ: relationship of extent of noninvasive disease to the frequency of occult invasion, multicentricity, lymph node metastases, and short-term treatment failures. Cancer 1982;50:13091314. 35. Holland R, Peterse J, Millis R, et al. Ductal carcinoma in situ: a proposal for a new classication. Semin Diagn Pathol 1994;11(3):167180. 36. Silverstein MJ, Poller D, Waisman J, et al. Prognostic classication of breast ductal carcinoma-in-situ. Lancet 1995;345:11541157. 37. Jensen J, Handel N, Silverstein M, et al. Glandular replacement therapy (GRT) for intraductal breast carcinoma (DCIS). Proc Am Soc Clin Oncol 1995;14:138. 38. Jensen J, Handel N, Silverstein M. Glandular replacement therapy: an argument for a combined surgical approach in the treatment of noninvasive breast cancer. Breast J 1996;2: 121123. 39. Faverly D, Burgers L, Bult P, et al. Three dimensional imaging of mammary ductal carcinoma is situ: clinical implications. Semin Diagn Pathol 1994;11(3):193198. 40. Poller D, Silverstein M, Galea M, et al. Ductal carcinoma in situ of the breast: a proposal for a new simplied histological classication association between cellular proliferation and c-erbB-2 protein expression. Modern Pathol 1994;7:257262. 41. Bellamy C, McDonald C, Salter D, et al. Noninvasive ductal carcinoma of the breast: the relevance of histologic categorization. Hum Pathol 1993;24:1623. 42. Sloane J, Ellman R, Anderson T, et al. Consistency of histopathological reporting of breast lesions detected by breast screening: ndings of the UK national external quality assessment (EQA) scheme. Eur J Cancer 1994;10:14141419. 43. Nielson M, Thomsen J, Primdahl S, et al. Breast cancer and atypia among young and middle-aged women; a study of 110 medicolegal autopsies. Br J Cancer 1987;56:814819. 44. Page D, Rogers L, Schuyler P, et al. The natural history of ductal carcinoma in situ of the breast. In: Silverstein MJ, Recht A, Lagios M, eds. Ductal Carcinoma in Situ of the Breast. Philadelphia: Lippincott, Williams and Wilkins; 2002:1721. 45. Sanders M, Schuyler P, Dupont W, et al. The natural history of low-grade ductal carcinoma in situ of the breast in women treated by biopsy only revealed over 30 years of long-term follow-up. Cancer 2005;103:24812484. 46. Rosen P, Senie R, Schottenfeld D, et al. Noninvasive breast carcinoma: frequency of unsuspected invasion and implications for treatment. Ann Surg 1979;1989:377382. 47. Alpers C, Wellings S. The prevalence of carcinoma in situ in normal and cancer-associated breast. Hum Pathol 1985;16:796807. 48. Page D, Dupont W, Roger L, et al. Intraductal carcinoma of the breast: follow-up after biopsy only. Cancer 1982;49:751758. 49. Schuh M, Nemoto T, Penetrante R, et al. Intraductal carcinoma: analysis of presentation, pathologic ndings, and outcome of disease. Arch Surg 1986;121:13031307. 50. Gump F, Jicha D, Ozzello L. Ductal carcinoma in situ (DCIS): a revised concept. Surgery 1987;102:190195.

Chapter 7 Ductal Carcinoma In Situ


86. Giordano S, Kuo Y, Freeman J, et al. Risk of cardiac death after adjuvant radiotherapy for breast cancer. J Natl Cancer Inst 2005;97:419424. 87. Darby S, McGale P, Taylor C, et al. Long-term mortality from heart disease and lung cancer after radiotherapy for early breast cancer: prospective cohort study of about 300,000 women in US SEER cancer registries. Lancet Oncol 2005;6:557565. 88. Zablotska L, Neugut A. Lung carcinoma after radiation therapy in women treated with lumpectomy or mastectomy for primary breast carcinoma. Cancer 2003;97:14041411. 89. Darby S, McGale P, Peto R, et al. Mortality from cardiovascular disease more than 10 years after radiotherapy for breast cancer: nationwide cohort study of 90,000 Swedish women. BMJ 2003;326:256257. 90. Recht A. Randomized trial overview. In: Silverstein MJ, Recht A, Lagios M, eds. Ductal Carcinoma in Situ of the Breast. Philadelphia: Lippincott, Williams and Wilkins; 2002:414419. 91. Wong J, Kaelin C, Troyan S, et al. Prospective study of wide excision alone for ductal carcinoma in situ of the breast. J Clin Oncol 2006;24(7):10311036. 92. Carlson RW, Allred DC, Anderson BO, et al. NCCN Clinical Practice Guidelines in Oncology: Breast Cancer. J Natl Compr Canc Netw 2009;7:122192. 93. Bijker N, Peterse J, Duchateau L, et al. Risk factors for recurrence and metastasis after breast-conserving therapy for ductal carcinoma in situ: analysis of European Organization for Research and Treatment of Cancer Trial 10853. J Clin Oncol 2001;19:22632271. 94. Fisher E, Constantino J, Fisher B, et al. Pathologic ndings from the National Surgical Adjuvant Breast Project (NSABP) protocol B-17. Cancer 1995;75:13101319. 95. Fisher B, Bauer M, Margolese R, et al. Five-year results of a randomized clinical trial comparing total mastectomy and lumpectomy with or without radiation therapy in the treatment of breast cancer. N Engl J Med 1985;312:665673. 96. Fisher E, Lemming R, Andersen S, et al. Conservative management of intraductal carcinoma (DCIS) of the breast. J Surg Oncol 1991;47:139147. 97. Allred D, Bryant J, Land S, et al. Estrogen receptor expression as a predictive marker of effectiveness of tamoxifen in the treatment of DCIS: ndings from NSABP protocol B-24. Breast Cancer Res Treat 2003;76(suppl 1):36. 98. Bijker N, Meijnen P, Peterse J, et al. Breast conserving treatment with or without radiotherapy in ductal carcinoma in situ: ten-year results of European Organization for Research and Treatment of Cancer Randomized Phase III Trial 10853a study by the EORTC Breast Cancer Cooperative Group and EORTC Radiotherapy Group. J Clin Oncol 2006;24:18. 99. Silverstein MJ, Barth A, Poller D, et al. Ten-year results comparing mastectomy to excision and radiation therapy for ductal carcinoma in situ of the breast. Eur J Cancer 1995; 31A(9):14251427. 100. Silverstein MJ, Lagios M, Groshen S, et al. The inuence of margin width on local control in patients with ductal carcinoma in situ (DCIS) of the breast. New Engl J Med 1999;340: 14551461. 101. Silverstein MJ, Buchanan C. Ductal carcinoma in situ: USC/Van Nuys Prognostic Index and the impact of margin status. Breast 2003;12:457471.

95

102. Silverstein MJ The University of Southern California/Van Nuys Prognostic Index for ductal carcinoma in situ of the breast. Am J Surg 2003;186:337343. 103. Ottesen G, Graversen H, Blichert-Toft M, et al. Ductal carcinoma in situ of the female breast. Short-term results of a prospective nationwide study. Am J Surg Pathol 1992;16: 11831196. 104. Silverstein MJ, Lagios M, Craig P, et al. The Van Nuys Prognostic Index for ductal carcinoma in situ. Breast J 1996;2:3840. 105. Silverstein MJ, Lagios M, Recht A, eds. Ductal Carcinoma in Situ of the Breast. 2nd ed. Philadelphia: Lippincott, Williams and Wilkins; 2002. 106. Poller D, Silverstein MJ. The Van Nuys ductal carcinoma in situ classication: an update. In: Silverstein MJ, Recht A, Lagios M, eds. Ductal Carcinoma in Situ of the Breast. Philadelphia: Lippincott, Williams and Wilkins; 2002:222233. 107. Silverstein MJ. The University of Southern California/Van Nuys Prognostic Index. In: Silverstein MJ, Recht A, Lagios M, eds. Ductal Carcinoma in Situ of the Breast. Philadelphia: Lippincott, Williams and Wilkins; 2002:459473. 108. Fisher E, Dignam J, Tan-Chie E, et al. Pathologic ndings from the National Adjuvant Breast Project (NSABP) eight-year update of protocol B-17: intraductal carcinoma. Cancer 1999;86:429438. 109. Silverstein MJ, Rosser R, Gierson E, et al. Axillary lymph node dissection for intraductal carcinomais it indicated? Cancer 1987;59:18191824. 110. Silverstein MJ An argument against routine use of radiotherapy for ductal carcinoma in situ. Oncology 2003;17(11):15111546. 111. Frykberg E, Masood S, Copeland E, et al. Duct carcinoma in situ of the breast. Surg Gynecol Obstet 1993;177:425440. 112. Anderson B, Masetti R, Silverstein M. Oncoplastic approaches to partial mastectomy: an overview of volume displacement techniques. Lancet Oncol 2005;6:145157. 113. Silverstein MJ, Handel N, Hoffman R, et al. The breast centera multidisciplinary model. In: Paterson AHG, Leeds AW, eds. Fundamental Problems in Breast Cancer. Boston: Martinus Nijhoff; 1987:4758. 114. Fleming ID, Cooper JS, Henson DE, et al. AJCC Cancer Staging Manual. 5th ed. Philadelphia: Lippincott-Raven; 1997. 115 Silverstein M, Lagios M, Recht A, et al. Image-detected breast cancer: state of the art diagnosis and treatment. J Am Coll Surg. 2005;201:586597. 116. Tabar L, Smith RA, Vitak B, et al. Mammographic screening: a key factor in the control of breast cancer. Cancer J. Jan-Feb 2003;9(1):1527. 117. Duffy SW, Tabar L, Smith RA. Screening for breast cancer with mammography. Lancet. Dec 2229 2001;358(9299):2166; author reply 21672168. 118. Silverstein MJ, Cohlan B, Gierson E, et al. Duct carcinoma in situ: 227 cases without microinvasion. Eur J. Cancer. 1992;28(2/3):630634. 119. Lagios MD. Duct carcinoma in situ: pathology and treatment. Surgical Clinics of North America. 1990;70:853871.

CHAPTER

8
Mastectomy for Breast Cancer
INTRODUCTION
Breast cancer has been recorded in human history since approximately 3000 BCE, as documented in the Edwin Smith Papyrus (1). At that time, there was little that could be done to help individuals aficted with this disease. Since then, the treatment of breast cancer has evolved with the increased understanding of the disease process and the development of newer methods to evaluate and treat breast cancer. In 1894, Halsteds mastectomy approach was part of the surgical revolution that transformed the operative treatment of breast cancer, and it is the gold standard against which all subsequent treatments have been compared. Since Halsteds time, the trend in the surgical management of breast cancer has been toward less extensive surgery. Breast-conserving surgery has become the preferred recommendation for patients who are acceptable candidates. There are, however, still a signicant number of patients who are not candidates for or do not want breast-conserving surgery, so mastectomy remains an important treatment modality for breast cancer. Mastectomy rates vary from 30% to 50%, with some of the variation attributed to practice patterns in different geographic regions. There has been a reported increase in the number of mastectomies being performed over the last decade (2). For any patient with breast cancer (invasive or noninvasive), the option of mastectomy must be offered and discussed in detail. This chapter provides information about invasive breast carcinoma and its treatment. To that end, the procedure of a mastectomy is discussed. Breast cancer comprises a number of different varieties. It arises in the terminal ductal-lobular unit (Fig. 8.1). The vast majority of breast cancers arise from the epithelial lining of the duct or the lobule and can be either invasive (inltrating ductal carcinoma or inltrating lobular carcinoma) or noninvasive (ductal carcinoma in situ or lobular carcinoma in situ [LCIS]). Although LCIS is not treated as cancer, it is considered a marker for increased risk and is included in the American Joint Committee on Cancer (AJCC) staging. This chapter deals with mastectomy as treatment for patients with invasive breast cancer or ductal carcinoma in situ. PRIMARY TUMOR (T)

Shawna C. Willey Donna-Marie E. Manasseh

TX: Primary tumor cannot be assessed T0: No evidence of primary tumor Tis: Carcinoma in situ (intraductal carcinoma, lobular carcinoma in situ, or Pagets disease of the nipple with no associated invasion of normal breast tissue) Tis (DCIS): Ductal carcinoma in situ Tis (LCIS): Lobular carcinoma in situ Tis (Pagets): Pagets disease of the nipple with no tumor Note: Pagets disease associated with a tumor is classied according to the size of the tumor. T1: Tumor less than or equal to 2.0 cm in greatest dimension T1mi: Microinvasion less than or equal to 0.1 cm in greatest dimension T1a: Tumor greater than 0.1 cm but less than or equal to 0.5 cm in greatest dimension T1b: Tumor greater than 0.5 cm but less than or equal to 1.0 cm in greatest dimension T1c: Tumor greater than 1.0 cm but less than or equal to 2.0 cm in greatest dimension T2: Tumor greater than 2.0 cm but less than or equal to 5.0 cm in greatest dimension T3: Tumor greater than 5.0 cm in greatest dimension T4: Tumor of any size with direct extension to (a) chest wall or (b) skin, only as described here: T4a: Extension to chest wall, not including pectoralis muscle T4b: Edema (including peau dorange) or ulceration of the skin of the breast, or satellite skin nodules conned to the same breast T4c: Both T4a and T4b T4d: Inammatory carcinoma REGIONAL LYMPH NODES (N) NX: Regional lymph nodes cannot be assessed (e.g., previously removed) N0: No regional lymph node metastasis N1: Metastasis to movable ipsilateral level I, II axillary lymph node(s) N2: Metastasis in ipsilateral level I, II axillary lymph node(s) xed or matted, or in clinically apparent ipsilateral internal mammary nodes in the absence of clinically evident lymph node metastasis N2a: Metastasis in ipsilateral axillary lymph nodes xed to one another (matted) or to other structures N2b: Metastasis only in clinically apparent ipsilateral internal mammary nodes and in the absence of clinically evident axillary lymph node metastasis N3: Metastasis in ipsilateral infraclavicular (level III axillary) lymph node(s) with or without level I, II axillary lymph node

STAGING OF BREAST CANCER


The staging system for breast cancer has undergone many revisions with the development of new technology and a greater understanding of the disease process. Here we present the most recent (2003) revision of the staging system by the AJCC (3) (Table 8.1). It is a clinical and pathologic system based on the TNM (tumor, node, and metastasis) classification. This staging system takes into account sentinel node status, immunohistochemistry staining, and the presence of micrometastases.

96

Chapter 8 Mastectomy for Breast Cancer

97

Rib Muscle

Lobes Ducts

Nipple Areola

Fat

Figure 8.1. Breast anatomy.

TABLE 8.1
Stage 0 Stage IA Stage IB Stage IIA

American Joint Committee on Cancer Stage Groupings


Tis, N0, M0 T1*, N0, M0 T0, N1mi, M0 T1*, N1mi, M0 T0, N1, M0 T1*, N1, M0 T2, N0, M0 T2, N1, M0 T3, N0, M0 T0, N2, M0 T1*, N2, M0 T2, N2, M0 T3, N1, M0 T3, N2, M0 T4, N0, M0 T4, N1, M0 T4, N2, M0 Any T, N3, M0 Any T, any N, M1

involvement, or in clinically apparent ipsilateral internal mammary lymph node(s) and in the presence of clinically evident level I, II axillary lymph node metastases; or metastases in ipsilateral supraclavicular lymph node(s) with or without axillary or internal mammary lymph node involvement N3a: Metastases in ipsilateral infraclavicular lymph node(s) N3b: Metastases in ipsilateral internal mammary lymph node(s) and axillary lymph node(s) N3c: Metastases in ipsilateral supraclavicular lymph node(s) Note: Clinically detected is defined as detected by imaging studies (excluding lymphoscintigraphy) or by clinical examination and having characteristics highly suspicious for malignancy. PATHOLOGIC CLASSIFICATION (PN) pNX: Regional lymph nodes cannot be assessed (e.g., not removed for pathologic study or previously removed) pN0: No regional lymph node metastases identied histologically Note: Isolated tumor cell clusters (ITC) are dened as small clusters of cells not greater than 0.2 mm, or single tumor cells, or a cluster of fewer than 200 cells in a single histologic cross-section. ITCs may be detected by routine histology or by immunohistochemical (IHC) methods. Nodes containing only ITCs are excluded from the total positive node count for purposes of N classication but should be included in the total number of nodes evaluated.

Stage IIB Stage IIIA

Stage IIIB

Stage IIIC Stage IV


* **

T1 includes T1mi. T0 and T1 tumors with nodal micrometastases only are excluded from Stage IIA and are classied Stage IB.

98

Section I Oncology and Oncoplastic Surgery

pN0(i): No regional lymph node metastases histologically, negative IHC pN0(i): Malignant cells in regional lymph node(s) no greater than 0.2 mm (detected by H&E or IHC including ITC) pN0(mol): No regional lymph node metastases histologically, negative molecular findings (reverse transcriptase polymerase chain reaction [RT-PCR]) pN0(mol): Positive molecular ndings (RT-PCR), but no regional lymph node metastases detected by histology or IHC Note: Classication is based on axillary lymph node dissection with or without sentinel lymph node dissection. Classication based solely on sentinel lymph node dissection without subsequent axillary lymph node dissection is designated (sn) for sentinel node; for example, pN0(I) (sn). pN1: Micrometastases; or metastases in 1 to 3 axillary lymph nodes; and/or in internal mammary nodes with metastases detected by sentinel lymph node biopsy but not clinically detected pN1mi: Micrometastases (greater than 0.2 mm and/or more than 200 cells, but none greater than 2.0 mm) pN1a: Metastases in 1 to 3 axillary lymph nodes, at least one metastasis greater than 2.0 mm pN1b: Metastases in internal mammary nodes with micrometastases or macrometastases detected by sentinel lymph node biopsy but not clinically detected pN1c: Metastases in 1 to 3 axillary lymph nodes and in internal mammary lymph nodes with micrometastases or macrometastases detected by sentinel lymph node biopsy but not clinically detected pN2: Metastases in 4 to 9 axillary lymph nodes; or in clinically detected internal mammary lymph nodes in the absence of axillary lymph node metastases pN2a: Metastases in 4 to 9 axillary lymph nodes (at least one tumor deposit greater than 2.0 mm) pN2b: Metastases in clinically detected internal mammary lymph nodes in the absence of axillary lymph node metastases pN3: Metastases in 10 or more axillary lymph nodes; or in infraclavicular (level III axillary) lymph nodes; or in clinically detected ipsilateral internal mammary lymph nodes in the presence of 1 or more positive level I, II axillary lymph nodes; or in more than 3 axillary lymph nodes and in internal mammary lymph nodes with micrometastases or macrometastases detected by sentinel lymph node biopsy but not clinically detected; or in ipsilateral supraclavicular lymph nodes pN3a: Metastases in 10 or more axillary lymph nodes (at least one tumor deposit greater than 2.0 mm); or metastases to the infraclavicular (level III axillary lymph) nodes pN3b: Metastases in clinically detected*** ipsilateral internal mammary lymph nodes in the presence of 1 or more positive axillary lymph nodes; or in more than 3 axillary lymph nodes and in internal mammary lymph nodes with micrometastases or macrometastases detected by sentinel lymph node biopsy but not clinically detected pN3c: Metastases in ipsilateral supraclavicular lymph node(s) Note: Clinically apparent is defined as detected by imaging studies (excluding lymphoscintigraphy) or by clinical examination. Not clinically apparent is dened as not detected by imaging studies (excluding lymphoscintigraphy) or by clinical examination.

DISTANT METASTASIS (M) M0: No clinical or radiographic evidence of distant metastases M1: Distant detectable metastases as determined by classic clinical and radiographic means and/or histologically proven larger than 0.2 mm cMo(i): No clinical or radiographic evidence of distant metastases, but deposits of molecularly or microscopically detected tumor cells in circulating blood, bone marrow or other non-regional nodal tissue that are no larger than 0.2 mm in a patient without symptoms or signs of metastases

MASTECTOMY
HISTORICAL PERSPECTIVE One of the earliest recorded operative approaches to the treatment of breast cancer dates to the 18th century when Jean Louis Petit advocated removal of the breast, pectoral muscles, and axillary lymph nodes to treat the disease (4). Since then, several operations have been described for the treatment of breast cancer. Most notably, in 1894, William Halsted described what is referred to today as the Halstedian radical mastectomy. In his landmark study, Halsted described his surgical attack on breast cancer. He stated, the suspected tissue should be removed in one piece (5). This is done by complete en bloc resection of the breast with the pectoralis major muscle and regional lymphatics. With this approach, Halsted achieved a decrease in local recurrence rates of 6% and regional recurrence rates of 22% from rates of 51% to 82% for surgeons of his day (57). Approximately 10 days after Halsteds study appeared in print, Willy Meyer published his technique for radical mastectomy (8). Although it was similar to Halsteds approach, there are some differences that warrant mentioning. In Halsteds approach, the pectoralis major muscle with the overlying breast tissue was dissected from the underlying sternum and the chest wall prior to removal of the axillary contents. In Meyers approach the axilla was dissected prior to the resection of the breast and pectoral muscles. In addition, Halsted simply divided the pectoralis minor muscle and left it in situ, whereas Meyer advocated removal of the pectoralis minor as well. Both Halsted and Meyer used vertical incisions; however, Halsted regularly sacriced much more skin (taking as much skin as possible on all sides of the tumor) than in Meyers approach. A skin graft was often required to cover the chest wall defect with Halsteds approach. In both Halsteds and Meyers approaches, all three nodal levels from the latissimus dorsi laterally to the thoracic outlet medially were removed (8,9). Both approaches sacriced the long thoracic nerve and the thoracodorsal neurovascular bundle en bloc with the axillary contents. These approaches, believed necessary at the time as evidenced by the substantial decrease in recurrence rates with these operations, left women disgured and with signicant disabilities such as winged scapula, lymphedema, and shoulder xation. There have since been several modications in the surgical treatment of the breast in an effort to decrease the morbidity associated with these operations while preserving the improved disease-free survival that had been noted with Halsteds approach. In the 1940s, Patey (10,11) advocated preservation of the pectoralis major muscle. It was noted that this procedure was equivalent in terms of local relapse rate and overall survival to the results for patients treated with the previously described standard radical mastectomy. Haagensen (12), in the early 1970s, advocated preservation of the long thoracic nerve to avoid the winged

Chapter 8 Mastectomy for Breast Cancer

99

scapula disability. He stated that it was unnecessary to remove this nerve to achieve adequate surgical treatment of breast cancer. In the 1960s, Auchincloss (13) and Madden (14), in contrast to Patey, advocated preservation of both pectoralis major and minor muscles. With this modication, only level I and level II nodes were easily accessible, and the dissection of level III nodes was restricted. Auchincloss (13) further stated that removal of level III nodes was necessary only if they were clinically involved because of the high recurrence rate if positive nodes were left in place. The Auchincloss modication of the radical mastectomy is most consistent with the modied radical mastectomy of today. Further modication of the modied radical mastectomy occurred with the development of the total mastectomy. This procedure preserves both pectoralis muscles and the axillary lymph nodes. The rationale for this modication stems from the popularization of the hypothesis that breast cancer is a systemic disease (15). Based on this hypothesis, the regional nodal dissection is unnecessary in the clinically negative axilla because it is unlikely to affect survival. Several retrospective and prospective studies (1618) sought to prove the hypothesis that breast cancer is a systemic disease early in its course. Most notable of these is the prospective randomized study by Fisher and the National Surgical Adjuvant Breast and Bowel Project (NSABP). In the 1970s, NSABP B-04 (15) compared total mastectomy with and without axillary radiation to standard radical mastectomy. This study, which demonstrated no statistically signicant difference in diseasefree survival between the study arms, supported the notion that aggressive surgical management does not change survival in a disease that is systemic and heralded the introduction of a more minimal approach to the surgical treatment of breast cancer. Included in this minimalist approach is preservation of muscles, lymph nodes, and even skin. Toth and Lappert rst used the term skin-sparing mastectomy (SSM) in 1991 (19). They described preoperative planning of mastectomy incisions in an attempt to maximize skin preservation and facilitate immediate breast reconstruction. Skin-sparing mastectomy (in which the nipple-areola complex and a minimal amount of skin are removed) is commonly used in patients who desire immediate reconstruction. Preservation of the inframammary fold (IMF) and the native skin envelope enhances the aesthetic result of breast reconstruction. Taking the minimalist approach even further is total skin-sparing mastectomy (nipple-sparing mastectomy), which is under investigation in the prophylactic setting as well as for selected patients with breast cancer. Similarly, breast conservation has evolved as part of the trend toward less surgery for breast cancer. A brief discussion is presented here for reference, but details are presented in Chapter 10. Breast conservation involves removal of the primary tumor with an adequate margin of normal breast parenchyma. It is followed by radiation therapy in order to provide equivalent survival rates to that achieved with mastectomy as demonstrated in the NSABP B-06 (20) and European Organisation for Research and Treatment of Cancer trials (21). Breast-conserving surgery is also referred to as lumpectomy, partial mastectomy, and segmental mastectomy. Any woman is a candidate provided the following criteria are met: The removal of the primary breast tumor with an adequate margin of normal breast parenchyma is accomplished while maintaining an acceptable cosmetic result. The patient can tolerate the recommended radiation therapy regimen.

Positive axillary nodes on clinical or pathologic examination are not a contraindication to breast conservation. INDICATIONS FOR MASTECTOMY Almost all women with breast cancer are candidates for mastectomy. The specic type of mastectomy performed relies on the presentation of the patient and her disease. Differentiation between total mastectomy and skin-sparing mastectomy is a somewhat arbitrary denition, as the dening factor between the two is the amount of skin left intact to accomplish reconstruction. The Halstedian mastectomy is of historic interest today. There are occasions when excision of muscle invaded by tumor is performed en bloc during a mastectomy; however, with the availability of multimodality therapy, radiation therapy and adjuvant chemotherapy are used to improve outcome in those patients with locally advanced disease. Indications for mastectomy are as follows: The presence of two or more primary tumors in separate quadrants or diffuse malignant calcications Invasive carcinoma with an extensive DCIS component Persistent positive margins after multiple surgical attempts with partial mastectomy Recurrence in a breast previously treated with partial mastectomy and radiation Tumor size relative to breast size that does not allow for breast conservation and an acceptable cosmetic outcome Contraindication to receiving radiation treatment to the breast (collagen-vascular disease, pregnancy) Patient preference in those considered at high risk (gene mutation carriers for BRCA1/BRCA2 or strong family history), in which case bilateral mastectomy may be considered The indications for modied radical mastectomy are similar to those for total mastectomy as it relates to the treatment of disease in the breast. The difference lies in the surgical approach to the axilla. If a patient has biopsy-proven involvement of an axillary lymph node or circumstances that exclude her from undergoing a sentinel node biopsy, then an axillary dissection in conjunction with the mastectomy is performed (i.e., a modied radical mastectomy). ANATOMIC CONSIDERATIONS The female breast is an apocrine gland arising from a skin appendage, a so-called modied sweat gland. It is enclosed between the supercial and deep layers of the supercial fascia of the anterior abdominal wall. The supercial layer is a very delicate, but definite structure that can be seen in most patients. It is not as well dened in fatty breasts and along the IMF (22). Large vessels lie deep to this plane that send vertical branches to the subdermal plexus (23). Coopers ligaments are peripheral projections of breast tissue in brous processes, which fuse with the supercial layer of the supercial fascia (23). Skiles demonstrated that these projections were intimately associated with the skin, with the conclusion that, to excise the whole breast, a large amount of skin must be sacriced or the dissection kept so close to the skin as to risk necrosis (23). This was the rationale for the use of the radical mastectomy proposed by Halsted (24). The retromammary plane is a well-dened space that lies between the deep layer of the supercial fascia on the posterior aspect of the breast and the fascia covering the pectoralis major

100

Section I Oncology and Oncoplastic Surgery

muscle. It contains loose areolar tissue, which allows for a degree of mobility of the breast over the chest wall and can easily be visualized as a denite anatomic plane on mammography. There are projections of the deep layer of the supercial fascia that cross the retromammary space and fuse with the pectoral fascia. These form the posterior suspensory ligaments of the breast. Skiles showed that small islands of the breast parenchyma might accompany these brous processes, which are attached to the pectoral fascia (23). Hicken, in 1940, outlined the extent of mammary tissue on the chest wall by injecting x-ray contrast material into the lactiferous ducts of 385 mastectomy specimens (25). He demonstrated that in 95% of cases the ducts ascended into the axilla; 15% passed into the epigastric space, and 2% followed the lateral chest wall beyond the anterior border of the latissimus dorsi muscle. This study dened the classic boundaries of a mastectomy: the clavicle, the rectus sheath, the midline of the sternum, and the anterior border of the latissimus dorsi muscle. This is why, regardless of the skin incision used, the boundaries of dissection of a mastectomy are as follows (Fig. 8.2): Lateral: the anterior border of the latissimus dorsi muscle. Medial: the sternal border. Superior: the lower border of the clavicle. Inferior: the caudal extension of the breast (at the inferior margin of the pectoralis major muscle at the sixth and occasionally the seventh rib) (12) identied by a layer of loose areolar tissue resembling tissue paper, sometimes referred to at our institution as the crinkly layer (Fig. 8.3). This region generally corresponds to the location of the inframammary fold and corresponds to the location of the separation of the supercial and deep layers of the supercial fascia to the abdominal wall. TECHNIQUE The modied radical mastectomy in its simplest description is a resection of the entire breast, nipple-areolar complex, axillary lymph nodes (levels I, II, and occasionally III if involved), and the skin overlying the tumor. A total mastectomy is similar to the modied radical mastectomy in terms of the dissection of the breast; however, no axillary node dissection is performed. A skin-sparing mastectomy differs from a total mastectomy only by the amount of

Figure 8.3. Crinkly layer at the inferior border of the breast.

skin that is removed, which is dictated by tumor size and location, breast size, type of reconstruction, patient preference for reconstructed breast size, and degree of ptosis of the breast. Although there are various modications, the description provided here represents the most common form used by surgeons today.

Skin Incision
The choice of skin incision depends on the location of the primary tumor and whether immediate reconstruction is planned (Fig. 8.4). The nipple-areolar complex is removed. The previous biopsy scar, if one exists, is excised as necessary to ensure clear margins. The location of the primary tumor determines the site of the incision. The location and type of incision also depend on whether immediate, delayed, or no reconstruction is planned (Fig. 8.5). If delayed reconstruction is considered, consultation with a plastic surgeon before mastectomy is desirable. If immediate reconstruction is planned, the oncologic and plastic surgeons should plan the incision together, and the skin and surface anatomy should be marked (Fig. 8.6). Oncologic principles take precedence over cosmetic concerns. Generally, a skin-sparing incision is used if immediate reconstruction is planned, provided adequate margins can be obtained. Any type of reconstruction can be used with a skin-sparing mastectomy, although the skin incision will differ depending on whether an expander is to be placed or there is autologous tissue transfer. Based on incision placement and size, an axillary incision is sometimes needed to facilitate a sentinel node biopsy or axillary dissection, especially if access to the axilla is not easily attained without putting stretch on the aps. If no reconstruction is planned, then a transverse or slightly oblique elliptical incision is used (Fig. 8.7). Axillary surgery can generally be performed through this incision without the need for a separate axillary incision. Vertical incisions as used in the time of Halsted should be avoided because they can limit upper extremity range of motion.

Flap
Figure 8.2. Mastectomy boundaries of dissection.
The thickness of the skin ap that is elevated is often debated among surgeons. Haagensens (26) recommendation, which is

Chapter 8 Mastectomy for Breast Cancer

101

Central

Upper outer

Upper inner

Lower outer

Lower inner

Figure 8.4. Location of tumor.

still popular today, was to dissect just above the supercial layer of the superficial fascia of the breast. This layer allows the surgeon to dissect the skin aps in a relatively avascular plane and remove maximal mammary tissue. Ideal flap thickness remains controversial and varies among patients. In a two-arm study by Krohn et al. (27), ap thickness was evaluated in women undergoing radical mastectomy. Each arm included 45 women with comparable clinical stages to compare

ultrathin aps with thicker aps. The authors noted comparable 5- and 10-year survival and recurrence rates between both groups. However, an increased incidence of wound complications, length of hospital stay, and lymphedema were noted in the ultrathin group. More recently, Beer et al. (22) sought to examine the feasibility of using the supercial layer as a guide for adequate removal of breast tissue while maintaining viable skin aps. In that study, the authors found that the supercial

102

Section I Oncology and Oncoplastic Surgery

vs

Skin sparing

No reconstruction

Figure 8.5. Variety of incisions.


layer was absent in 44% of the resected specimens. They noted that when the supercial layer was present, there were islands of breast tissue within the supercial layer in 42% of the specimens. When present, the supercial layer had an undulating appearance rather than a straight, horizontal interface. Furthermore, the distance between the supercial layer and the dermis varied within a single specimen and across all specimens (from less than 5 mm in 82% to greater than 10 mm in 5.1%), as did the thickness of the supercial layer itself. There was no breast tissue noted between the supercial layer and the skin. If the supercial layer was not present, the distance between the breast tissue and the dermis varied from 0.8 to 14.0 mm. There was no correlation between the thickness of the subcutaneous fat and the body weight or body mass index (BMI). This is in contrast to ndings from other authors, who found a positive correlation between these parameters (26,28,29). Beer et al. (22) noted that, in some instances, it is virtually impossible to remove all breast tissue. Rather, they recommended looking for the presence of the supercial layer. If visible, it should be used as a plane of dissection, provided viable skin aps are left behind. If the supercial layer is not visible, then the goal of preserving viability of the skin aps should be weighed against the possibility of attempting to remove all possible breast tissue. At our institution, we aim to identify a plane of dissection that separates the visible breast tissue from the region just above the supercial layer. We have observed that this plane of dissection varies among patients, depending on body habitus, and leaves a ap thickness on average of 7 to 8 mm.

Dissection
The skin incision is made through the epidermis and the dermis until the underlying subcutaneous fat is barely visible. An edge is elevated below the dermis in the subcutaneous fat to allow for the application of clamps (Lahey or Adair) or skin hooks on the underside of the ap to minimize injury to the overlying skin. This is particularly important when reconstruction is being considered. Retraction with clamps or hooks should be spaced evenly with constant tension applied by the assistant at right angles to the chest wall. At the same time, the operating surgeon retracts the breast tissue away from the overlying skin. This maneuver allows visualization of the dissection plane and allows the development of a flap with a constant thickness throughout. Similarly, long, even strokes with a knife or cautery in parallel with the flap contribute to the evenness of the flap and minimize accidental burns (to

Figure 8.6. Preoperative markings for a skin-sparing mastectomy.

Figure 8.7. Marking for a mastectomy without reconstruction.

Chapter 8 Mastectomy for Breast Cancer

103

the dermis/ap) and button holes. In general, the goal is to develop a ap that removes enough breast tissue to meet oncologic requirements while maintaining the viability of the ap. Especially when performing a skin-sparing mastectomy, the aps must be handled carefully, and the use of deep abdominal retractors is minimized. Because the skin opening is small, the aps are elevated in a circular fashion to assist in exposure. It is technically more demanding and time consuming to perform a skin-sparing mastectomy. A lighted retractor or Bovie with a light attached are useful when dissecting the aps in the periphery, where visualization is more difcult. Traction necrosis can occur at the edges of the ap if care is not taken with tissue handling. The skin ap is elevated to the clavicle superiorly, the anterior border of the latissimus dorsi laterally, the sternal border medially, and the insertion of the rectus muscle inferiorly. At the inferior border, there is a layer of loose areolar tissue that indicates the inferior edge of dissection. The breast is then removed with the pectoralis major fascia from the superomedial border to the inferolateral border. The operating surgeon should maintain constant upward traction of the breast specimen. This tension allows for visualization of the pectoralis fascia layer, which is most easily removed parallel to the direction of the muscle bers. Damage to the underlying muscle can have an adverse effect on reconstruction. There are multiple perforators from the lateral thoracic or anterior intercostal arteries that are encountered during this stage of the procedure. These should be identied and either clamped and ligated or controlled with cautery. At the lateral aspect of the pectoralis major muscle, the muscle is retracted medially to expose the pectoralis minor muscle. Care should be taken to avoid injury to the lateral pectoral nerve as it curves around the lateral aspect of the pectoralis major (30) and the medial pectoral nerve, which can have various courses (31,32); injury to these can result in pectoralis major muscle atrophy, which can cause delayed shoulder dysfunction. At this time, the breast and the overlying skin with the nipple-areolar complex are removed en bloc with the pectoralis fascia. Serratus anterior fascia at the lateral border of the dissection and rectus fascia inferiorly should be kept intact. During a modied radical mastectomy, the axillary contents are usually removed en bloc with the breast specimen. In this scenario, the dissection continues as the breast specimen is retracted from the medial to lateral border. The lateral edge of the pectoralis major muscle is followed into the axilla. Clavipectoral fascia at the lateral aspect of the pectoralis minor is incised to afford access to the axilla. Full details of an axillary dissection are presented in the next chapter. The wound is irrigated and hemostasis is achieved with cautery or ligatures, where appropriate. In the region of the breast, a Jackson-Pratt or Blake drain is placed through a separate stab wound incision, inferior to the incision at the anterior axillary line and positioned under the inferior skin ap. This drain helps decrease seroma formation and facilitate ap adherence to the chest wall. In the area of the axilla, a drain may or may not be placed, depending on the surgeons preference, the extent of the dissection, the suspicion of extensive metastatic disease in the nodes, and the size of the space that remains after removal of the axillary contents. The incision is closed in two layers with absorbable suture if no reconstruction is planned, or it is left open with moist gauze in place while the area is prepared for the reconstructive portion of the procedure (Fig. 8.8).

Figure 8.8. Breast specimen with orientation suture after skin-sparing


mastectomy.

MORBIDITY/COMPLICATIONS A mastectomy is an operation with low morbidity and mortality and is well tolerated by patients. However, it is not without complications. Most notable are seroma formation, wound infection, skin ap necrosis, and, with the modied radical mastectomy, lymphedema. A seroma is a collection of uid (lymph/blood) in a surgically created cavity that results from the transection of vessels and lymphatics. The degree of seroma formation depends on several factors, including the following: Use of a closed suction drain beneath the skin aps as proposed by Murphy (33) in 1947. Extent of surgery (more extensive surgery leads to an increased likelihood of seroma formation) (34), although removal of the pectoralis fascia did not increase seroma formation (35). BMI (higher BMI translates to increased risk of seroma formation (3638). Several studies have shown no difference in seroma formation with the use of closed suction drains (39,40). In general, the use and duration of a closed suction drain is advocated in the area of the mastectomy aps and on an individual basis in the area of the axilla (if a modied radical mastectomy is performed). Wound infection rates range from 2.8% to 15% (4143). An infection can occur due to primary tissue ischemia secondary to extensive dissection of skin aps, creating tissue ischemia that can progress to tissue necrosis. If not debrided early enough, this area becomes a medium for bacterial overgrowth. The most common organisms identied are Staphylococcus aureus and Streptococcus epidermidis (44), and they should be treated with the appropriate antibiotic with or without opening the wound when indicated. Administration of preoperative antibiotics was once felt not to be necessary for a clean operation such as a mastectomy (45). Prophylactic antibiotics are now recommended since most patients going for mastectomy are at increased risk of infection because they have had either a preoperative core needle biopsy (45) or a recent previous open biopsy (46,47) and have an alteration of host defense (cancer) (34,44).

104

Section I Oncology and Oncoplastic Surgery

TABLE 8.2

Published Series of Local Recurrence (LR) of Breast Cancer after Skin-Sparing Mastectomy (SSM) and NonSkinSparing Mastectomy (Non-SSM) for Invasive Breast Cancer
Follow-up (mo)
41.3 72 60 49 73 117.6 49.2 50

Authors
Carlson et al. (54) Kroll et al. (55) Simmons et al. (56) Rivadeneira et al. (57) Medina-Franco et al. (58) Spiegel and Butler (59) Foster et al. (60) Newman et al. (61)

SSM (N)
187 114 77 71 176 177 54 437

LR in SSM (%)
4.8 7.0 3.9 5.6 4.5 5.6 4.0 6.2

Non-SSM (N)
84 40 154 127

LR in Non-SSM (%)
9.5 7.5 3.25 3.9

Necrosis of the skin aps after modied radical mastectomy occurs in 5% to 18% of patients (42,43). Although not as common as in the early days of breast surgery, ap necrosis is still observed. Factors that are believed to contribute to necrosis include the following: Inadequate blood supply to the ap Wound closure under tension External pressure from compression dressings Obesity Type of incision (vertical versus transverse) History of radiation Diabetes Increased body mass index (48) Smoking, with smokers having a signicantly higher rate of epidermolysis than nonsmokers, 49% versus 14% (p 0.01) (42)

been several nonrandomized studies comparing the local recurrence (LR) associated with SSM and conventional (nonSSM) techniques (Table 8.2) (5461). The LR rate in these studies ranged from 3.25% to 9.5%. There have been concerns that SSM should not be used in the treatment of invasive breast cancer. Studies that directly compared SSM and non-SSM have found no signicant differences in LR rates (5457). SSM and immediate reconstruction is associated with a low rate of local recurrence and low morbidity.

CONCLUSION
A mastectomy is an acceptable option for the treatment of anyone with breast cancer. As tumors are detected at increasingly smaller sizes, the need for more-minimal approaches ourishes. The surgeon, therefore, not only needs to understand the minimalist approach, but also needs to be able to understand and communicate the indications, techniques, and morbidity associated with mastectomy. Patients diagnosed with breast cancer will then be well informed about their treatment options and empowered to make informed decisions.

Two reviews reported the incidence of native skin ap necrosis after SSM to be 13.9% to 17.0% (48). Hultman and Daiza found that previous breast irradiation and diabetes were associated with SSM ap complications (48). Carlson et al. evaluated the technical safety of 633 SSMs (49). They found that tobacco smoking and previous breast irradiation predisposed to native skin loss. In cases where skin necrosis occurred, Hultman and Daiza recommended conservative management if possible, including the application of topical antimicrobial creams and minimal early debridement. Extensive necrosis is best treated by debridement after demarcation of ap viability (48). Lymphedema can affect as many as 30% of patients who undergo a modied radical mastectomy. Lymphedema is secondary to ablation of the lymphatic routes (nodes and channels) in the drainage pathway. Risk factors for the development of lymphedema include the extent of axillary dissection, in particular that which occurs near the axillary vein, radiation to the axilla, number of nodes removed, obesity, infection, and injury (5052). The incidence of lymphedema can be reduced by emphasis on patient education, avoidance of excessive skin exposure, infections or injury to the ipsilateral arm, and less-radical dissections. If lymphedema is noted, early intervention with physical therapy and decompressive massage can help prevent progression of the edema and, in some cases, reduce it. RECURRENCE Local recurrence after mastectomy is highly dependent on the stage of disease (53) and ranges from 0% to 25%. There have

EDITORIAL COMMENTS Manasseh and Willey presented us with a thorough review of the local management of breast cancer, including variations on mastectomy and dealing with the axilla. There are a couple of areas of concern in this chapter that are worth discussing. One has to do with the extent of dissection for a mastectomy. The authors report polystandard descriptions of a mastectomy going from the sternal border to the anterior border of the latissimus muscle and from the clavicle to below the inframammary fold. As a plastic surgeon, I would argue that those margins of dissection are probably excessive in virtually all women. By examining a patient, I think you can certainly determine the gross location of the breast. Particularly when the patient is recumbent, it often does not go as far medially as the medial sternal border, at least in small-breasted women. Even more so, the breast rarely appears to go anywhere nearly as high as the clavicle and also rarely goes below the inframammary fold. I would encourage general surgeons to think of resecting the breast

Chapter 8 Mastectomy for Breast Cancer

105

tissue or the vast majority of the breast tissue rather than removing all tissue from the clavicle to below the fold. The reasons for this have to do with the laws of diminishing returns. In all likelihood, as we get beyond the true margins of the breast, the utility of further resection in terms of treating the breast cancer drops off dramatically. However, the morbidity in terms of deformity increases dramatically. Resections above the true margins of the breast superiorly often create defects in the upper chest and infraclavicular area that are particularly conspicuous and hard to x. The same is true for overdissection medially. In a similar fashion, violating the inframammary fold is probably of minimal marginal benet in terms of treating the disease but disrupts a normal landmark that can be hard to repair later. A second issue of interest has to do with the effects of previous breast surgery and the value of sentinel node procedures. This would be true for such small procedures such as multiple previous biopsies or lumpectomies of the breast. However, in particular, as plastic surgeons we would be interested in having more information about the impact of breast augmentation, mastopexy, or breast reduction on the value of sentinel node procedures. The most interesting of all to plastic surgeons is the impact of transaxillary breast augmentation and whether that violates the effectiveness or value of sentinel node biopsy. Overall, this is an outstanding chapter both in terms of its review of the options for mastectomy and in bringing us up to date on the value of sentinel node approaches to the diagnosis and treatment of breast cancer. S.L.S. Dr. Spear raises excellent points that illustrate the value of the different perspectives of the oncologic and plastic surgeons and the necessity for each of them to understand the goals and challenges of the other. While we agree with Spear that there is individual variation in regard to the peripheral extent of the breast tissue, the oncologic surgeon must assess for breast tissue to the boundaries mentioned in this chapter, as the surface anatomy does not always predict the exact location of the edge of the breast tissue. In addition, the awareness of the anatomic location of breast tissue is necessary even during physical exam, as it is the peripheral lesion that will not be detected on mammography and is most commonly detected on physical exam. We have seen too many patients with recurrences in residual breast tissue after inadequate mastectomies to compromise on these standards. On the other hand, the oncologic surgeon must be aware of the consequences for the plastic surgeon of overenthusiastic extension of the margins and that preservation of the inframammary fold contributes greatly to a successful cosmetic outcome. S.C.W.

REFERENCES
1. Borgen PI, Heerdt AS, Moore MP, et al. Breast conservation therapy for invasive carcinoma of the breast. Curr Probl Surg 1995;32(3):191248. 2. McGuire KP, Santillan AA, Kaur P, et al. Are mastectomies on the rise? A 13-year trend analysis of the selection of mastectomy versus breast conservation therapy in 5865 patients. Ann Surg Oncol 2009;16(10):26822690. 3. Edge SB, Byrd DR, Compton CC, et al. AJCC cancer staging manual (7th ed). New York, NY: Springer; 2010.

4. Robbins G, ed. Silvergirls Surgery: The Breast. Austin, TX: Silvergirl; 1984. 5. Halsted W. The results of operations for the cure of cancer of the breast performed at The Johns Hopkins Hospital from June, 1889 to January, 1894. Johns Hopkins Hosp Bull 18941895;4:297. 6. Halsted W. The results of radical operations for the cure of cancer of the breast. Trans Am Surg Assoc 1907;25:61. 7. Cooper W. The history of the radical mastectomy. In: Hoeber PB, ed. Annals of Medical History, 3rd Ser. Vol. 3. New York: Paul B. Hoeber; 1941;36. 8. Meyer W. An improved method of the radical operations for carcinoma of the breast. Med Rec 1894;46:746. 9. Halsted W. Results of operations for cure of cancer of breast performed at Johns Hopkins Hospital from June 1889 to 9 January 1894. Ann Surg 1894;20:497. 10. Patey DH. A review of 146 cases of carcinoma of the breast operated on between 1930 and 1943. Br J Cancer 1967;21(2):260269. 11. Patey DH, Dyson WH. The prognosis of carcinoma of the breast in relation to the type of operation performed. Br J Cancer 1948;2(1):713. 12. Haagensen C. Anatomy of the mammary gland. In: Haagensen CD, ed. Diseases of the Breast. 2nd ed. Philadelphia: WB Saunders; 1971:154. 13. Auchincloss H. Signicance of location and number of axillary metastases in carcinoma of the breast. Ann Surg 1963;158:3746. 14. Madden JL. Modied radical mastectomy. Surg Gynecol Obstet 1965;121(6):12211230. 15. Fisher B, Redmond C, Fisher ER, et al. Ten-year results of a randomized clinical trial comparing radical mastectomy and total mastectomy with or without radiation. N Engl J Med 1985;312(11):674681. 16. Johansen H, Kaae S, Schiodt T. Simple mastectomy with postoperative irradiation versus extended radical mastectomy in breast cancer. A twenty-ve-year follow-up of a randomized trial. Acta Oncol 1990;29(6):709715. 17. Lythgoe JP, Palmer MK. Manchester regional breast study5 and 10 year results. Br J Surg 1982;69(12):693696. 18. Forrest AP, Stewart HJ, Roberts MM, et al. Simple mastectomy and axillary node sampling (pectoral node biopsy) in the management of primary breast cancer. Ann Surg 1982;196(3):371378. 19. Toth BA, Lappert P. Modied skin incisions for mastectomy: the need for plastic surgical input in preoperative planning. Plast Reconstr Surg 1991;87(6):10481053. 20. Fisher B, Bauer M, Margolese R, et al. Five-year results of a randomized clinical trial comparing total mastectomy and segmental mastectomy with or without radiation in the treatment of breast cancer. N Engl J Med 1985;312(11):665673. 21. van Dongen JA, Holland R, Peterse JL, et al. Ductal carcinoma in-situ of the breast; Second EORTC Consensus Meeting. Eur J Cancer 1992;28(23):626629. 22. Beer GM, Varga Z, Budi S, et al. Incidence of the supercial fascia and its relevance in skinsparing mastectomy. Cancer 2002;94(6):16191625. 23. Skiles H. Contributions to the surgical anatomy of the breast. Edinburgh Med J 1892;37: 1099. 24. Halsted W. The results of operations for the cure of cancer of the breast performed at The Johns Hopkins Hospital from June, 1889 to January, 1894. Johns Hopkins Hosp Bull 18941895;4:297. 25. Hicken N. Mastectomy: a clinical pathologic study demonstrating why most mastectomies result in incomplete removal of the mammary gland. Arch Surg 1940;40:614. 26. Haagensen C. Diseases of the Breast. 3rd ed. Philadelphia: WB Saunders; 1986. 27. Krohn IT, Cooper DR, Bassett JG. Radical mastectomy: thick vs thin skin aps. Arch Surg 1982;117(6):760763. 28. Carlson GW. Skin sparing mastectomy: anatomic and technical considerations. Am Surg 1996;62(2):151155. 29. Lockwood TE. Supercial fascial system (SFS) of the trunk and extremities: a new concept. Plast Reconstr Surg 1991;87(6):10091018. 30. Petrek JA, Blackwood MM. Axillary dissection: current practice and technique. Curr Probl Surg 1995;32(4):257323. 31. Moosman DA. Anatomy of the pectoral nerves and their preservation in modied mastectomy. Am J Surg 1980;139(6):883886. 32. Hoffman GW, Elliott LF. The anatomy of the pectoral nerves and its signicance to the general and plastic surgeon. Ann Surg 1987;205(5):504507. 33. Murphy D. The use of atmospheric pressure in obliterating axillary dead space following radical mastectomy. South Surg 1947;13:372. 34. Aitken DR, Minton JP. Complications associated with mastectomy. Surg Clin N Am 1983;63(6):13311352. 35. Dalberg K, Johansson H, Signomklao T, et al. A randomised study of axillary drainage and pectoral fascia preservation after mastectomy for breast cancer. Eur J Surg Oncol 2004;30(6): 602609. 36. Banerjee D, Williams EV, Ilott J, et al. Obesity predisposes to increased drainage following axillary node clearance: a prospective audit. Ann R Coll Surg Engl 2001;83(4):268271. 37. Burak WE Jr, Goodman PS, Young DC, et al. Seroma formation following axillary dissection for breast cancer: risk factors and lack of inuence of bovine thrombin. J Surg Oncol 1997;64(1):2731. 38. Forouhi P, Dixon JM, Leonard RC, et al. Prospective randomized study of surgical morbidity following primary systemic therapy for breast cancer. Br J Surg 1995;82(1):7982. 39. Puttawibul P, Sangthong B, Maipang T, et al. Mastectomy without drain at pectoral area: a randomized controlled trial. J Med Assoc Thai 2003;86(4):325331. 40. Jain PK, Sowdi R, Anderson AD, et al. Randomized clinical trial investigating the use of drains and brin sealant following surgery for breast cancer. Br J Surg 2004;91(1):5460. 41. Tejler G, Aspegren K. Complications and hospital stay after surgery for breast cancer: a prospective study of 385 patients. Br J Surg 1985;72(7):542544. 42. Vinton AL, Traverso LW, Jolly PC. Wound complications after modied radical mastectomy compared with tylectomy with axillary lymph node dissection. Am J Surg 1991;161(5):584588. 43. Budd DC, Cochran RC, Sturtz DL, et al. Surgical morbidity after mastectomy operations. Am J Surg 1978;135(2):218220.

106

Section I Oncology and Oncoplastic Surgery


54. Carlson GW, Bostwick J III, Styblo TM, et al. Skin-sparing mastectomy. Oncologic and reconstructive considerations. Ann Surg 1997;225(5):570575; discussion 575578. 55. Kroll SS, Khoo A, Singletary SE, et al. Local recurrence risk after skin-sparing and conventional mastectomy: a 6-year follow-up. Plast Reconstr Surg 1999;104(2):421425. 56. Simmons RM, Fish SK, Gayle L, et al. Local and distant recurrence rates in skin-sparing mastectomies compared with nonskin-sparing mastectomies. Ann Surg Oncol 1999;6(7): 676681. 57. Rivadeneira DE, Simmons RM, Fish SK, et al. Skin-sparing mastectomy with immediate breast reconstruction: a critical analysis of local recurrence. Cancer J 2000;6(5): 331335. 58. Medina-Franco H, Vasconez LO, Fix RJ, et al. Factors associated with local recurrence after skin-sparing mastectomy and immediate breast reconstruction for invasive breast cancer. Ann Surg 2002;235(6):814819. 59. Spiegel AJ, Butler CE. Recurrence following treatment of ductal carcinoma in situ with skin-sparing mastectomy and immediate breast reconstruction. Plast Reconstr Surg 2003;111(2):706711. 60. Foster RD, Esserman LJ, Anthony JP, et al. Skin-sparing mastectomy and immediate breast reconstruction: a prospective cohort study for the treatment of advanced stages of breast carcinoma. Ann Surg Oncol 2002;9(5):462466. 61. Newman LA, Kuerer HM, Hunt KK, et al. Presentation, treatment, and outcome of local recurrence after skin-sparing mastectomy and immediate breast reconstruction. Ann Surg Oncol 1998;5(7):620626.

44. Beatty JD, Robinson GV, Zaia JA, et al. A prospective analysis of nosocomial wound infection after mastectomy. Arch Surg 1983;118(12):14211424. 45. Witt A, Yavuz D, Walchetseder C, et al. Preoperative core needle biopsy as an independent risk factor for wound infection after breast surgery. Obstet Gynecol 2003;101(4):745750. 46. Wagman LD, Tegtmeier B, Beatty JD, et al. A prospective, randomized double-blind study of the use of antibiotics at the time of mastectomy. Surg Gynecol Obstet 1990;170(1):1216. 47. Platt R, Zaleznik DF, Hopkins CC, et al. Perioperative antibiotic prophylaxis for herniorrhaphy and breast surgery. N Engl J Med 1990;322(3):153160. 48. Hultman CS, Daiza S. Skin-sparing mastectomy ap complications after breast reconstruction: review of incidence, management, and outcome. Ann Plast Surg 2003;50(3):249255; discussion 255. 49. Carlson GW, Styblo TM, Lyles RH, et al. The use of skin sparing mastectomy in the treatment of breast cancer: The Emory experience. Surg Oncol 2003;12(4):265269. 50. Petrek JA, Senie RT, Peters M, et al. Lymphedema in a cohort of breast carcinoma survivors 20 years after diagnosis. Cancer 2001;92(6):13681377. 51. Herd-Smith A, Russo A, Muraca MG. Prognostic factors for lymphedema after primary treatment of breast carcinoma. Cancer 2001;92(7):17831787. 52. Kissin MW, Querci della Rovere G, Easton D, et al. Risk of lymphoedema following the treatment of breast cancer. Br J Surg 1986;73(7):580584. 53. Katz A, Strom EA, Buchholz TA, et al. Locoregional recurrence patterns after mastectomy and doxorubicin-based chemotherapy: implications for postoperative irradiation. J Clin Oncol 2000;18(15):28172827.

CHAPTER

9
INTRODUCTION
For patients with breast cancer, the most important prognostic factor is axillary node status. The principal goal of axillary surgery is staging/prognostication; secondary goals include local control and (arguably) a small survival benet. For most of the 20th century, these goals have been addressed by the historic gold standard, axillary lymph node dissection (ALND). Recently, ALND has given way to a new standard, sentinel lymph node (SLN) biopsy. This chapter will review the current status of SLN biopsy and ALND in the management of operable breast cancer.

Hiram S. Cody III

Sentinel Node Biopsy and Axillary Dissection


78 randomized trials) (12) and estimated that for every 4 local recurrences prevented, 1 life would be saved. Second, they conrmed that there is no survival advantage for more radical versus less radical versions of mastectomy (3,400 women in nine trials) or for mastectomy versus breast conservation (3,100 women in seven trials) (13). Finally, they demonstrated an incremental survival benet from the addition of systemic adjuvant therapy, chemotherapy, or hormonal therapy to local treatment (8,000 to 33,000 women in six separate meta-analyses comprising 194 trials) (14). These results highlight the multidisciplinary nature of contemporary breast cancer treatment and the importance of collaboration among the disciplines of surgery, medical oncology, and radiotherapy. The SLN concepts that (a) the rst, or rst few, regional lymph nodes draining a tumor site could predict the status of that regional node basin, (b) these nodes could be reliably mapped by injections of radiotracer or dye, and (c) SLN-negative patients might thereby avoid the added morbidity of regional node dissection were rst articulated by Cabanas (15) in 1977 for penile cancer and independently by Morton et al. (16) in 1992 for melanoma. Krag et al. (17) in 1993 (using isotope mapping) and Giuliano et al. (18) in 1994 (using blue dye) were the rst to report SLN biopsy for breast cancer. Since then, 69 observational series (19) of SLN biopsy (validated by a planned backup ALND) and the early results of seven randomized trials (2026) comparing SLN biopsy with ALND have conrmed that the morbidity of SLN biopsy is less than that of ALND, that staging accuracy is at least equivalent, and, in the single randomized trial reporting long-term results (27), that survival and other disease-related adverse events are comparable at 7 years followup. The SLN hypothesis has been validated by two elegant studies, one showing that a negative SLN is highly predictive of a negative axilla (28) and the other showing the SLN is the node likeliest to be positive (29). At present, virtually all node-negative breast cancer patients are staged by SLN biopsy alone, and the principal goal of ALND is to maximize local control in patients already proven by SLN biopsy to be node-positive.

HISTORICAL BACKGROUND
Jean Louis Petit (16741750), director of the French Surgical Academy, was probably the rst surgeon to articulate a unied concept for breast cancer surgery (1). He emphasized the importance of an en bloc resection of the breast and axillary nodes, but his insight came too early: Even by the mid-19th century, breast cancer was widely regarded as incurable by surgery. Halsteds landmark 1894 (2) and 1907 (3) reports of his meticulous technique for radical mastectomy (RM) (which included removal of the breast and pectoral muscles, with a complete ALND) suggested that reducing local recurrence would increase survival, and this intuitive concept made RM/ALND the standard operation for the next 70 years despite later reports of techniques that were either more radical (extended radical mastectomy) (4) or less radical (modied radical mastectomy) (5,6). In the Halstedian era, the goal was to maximize cure by minimizing local failure. In the 1970s, Fisher (7) proposed that breast cancer was a systemic disease from the outset and that survival was largely a function of tumor biology, not surgical technique. The Fisher hypothesis was tested in National Surgical Adjuvant Breast and Bowel Project (NSABP) B-04 randomized trial (19711974) (810); at 25 years follow-up, variations in local treatment for patients with clinically node-positive breast cancer (RM vs. total mastectomy/radiotherapy [RT]) or clinically node-negative disease (RM vs. total mastectomy/RT vs. total mastectomy alone) yielded no differences in any category of survival. B-04 did conrm the overwhelming prognostic signicance of axillary node metastasis, and ALND was incorporated into all subsequent NSABP trials for invasive breast cancer. In the Fisher era, the primary objective of ALND was prognostication to guide systemic therapy, a secondary objective was local control, and a survival benet was unproved. We now know that both Halsted and Fisher were right. A remarkable series of meta-analyses from the Early Breast Cancer Trialists Collaborative Group (EBCTCG) conrms that breast cancer is a family of diseases with a wide spectrum of behavior (11), ranging from predominantly local (Halsted) to predominantly systemic (Fisher) phenotypes. First, the EBCTCG showed that local control and survival are related (42,000 women in

CASE SELECTION FOR SENTINEL LYMPH NODE BIOPSY


As for any new surgical procedure, most institutions began to do SLN biopsy with caution, validating their early experience with a planned backup ALND to conrm an acceptably low false-negative rate (the proportion of node-positive patients in which the SLN was negative), limiting SLN biopsy to those patients with the lowest probability of axillary node metastasis, and avoiding SLN biopsy for a variety of putative but unproven contraindications. Among others, these included nonpalpable breast lesions, clinically suspicious axillary nodes, any prior breast or axillary surgery, large excisional biopsy, large tumor, multicentric tumor, prior RT, prior chemotherapy, male breast cancer, and pregnancy.

107

108

Section I Oncology and Oncoplastic Surgery

TABLE 9.1
Indications for SLN Biopsy

Indications for Sentinel Lymph Node (SLN) Biopsy and Axillary Lymph Node Dissection (ALND)
Indications for ALND
Axillary node metastasis on FNA or core biopsy Prior inadequate ALND Positive SLN on intraoperative exam Validation trials with planned backup ALND Palpably suspicious nodes during SLN biopsy Neoadjuvant chemotherapy for locally advanced (T4) disease Failed SLN biopsy Unavailability of SLN biopsy Axillary local recurrence (ipsilateral or contralateral)

Clinically node-negative T13 invasive (or microinvasive) breast cancer Clinically node-positive with negative preoperative ne-needle aspiration or core biopsy Following neoadjuvant chemotherapy for T23 disease Ductal carcinoma in situ requiring mastectomy or presenting as a mass Ipsilateral breast recurrence and prior SLN biopsy/ALND Prophylactic mastectomy

Based on an extensive literature (30), it is now clear that SLN biopsy is suitable for (a) virtually all operable invasive breast cancers with a clinically negative axilla, (b) ductal carcinoma in situ (DCIS) that requires mastectomy (or in which invasion is suspected based on the presence of a mass), and (c) breast cancer with clinically suspicious nodes when an ultrasoundguided ne-needle aspiration or core biopsy is nondiagnostic (Table 9.1). SLN biopsy is also reasonable in the setting of prophylactic mastectomy, where invasive cancer will be found in a small proportion of cases. SLN biopsy is feasible in patients previously operated for breast cancer (31,32), especially if fewer that ten nodes were removed in a prior SLN biopsy or ALND. Finally, SLN biopsy appears to work well after aesthetic breast surgery; two studies (33,34) have used lymphoscintigraphy to document preservation of the axillary lymphatic drainage following transaxillary breast augmentation, and in a series of 70 SLN biopsy procedures (50 patients with prior breast augmentation and 20 with prior breast reduction) (35), SLNs were identied at surgery in 100% of patients.

NUCLEAR MEDICINE The success of SLN biopsy is maximized, and the false-negative rate is minimized, by the combination of radioisotope and blue dye (22,38,39), but radioisotope accounts for the greatest proportion of this success, and with experience the marginal benet of blue dye diminishes (40). The isotope of choice is technetium (Tc99m) bound to a variety of carrier particles, most commonly sulfur colloid (United States), colloidal albumin (Europe), and antimony (Australia). There is no standardization of isotope dose, particle size, volume of injectate, timing of injection, or site of injection, and many methods appear to work well. Our preference is to inject 0.1 mCi (3.7 MBq) of unltered Tc99m-sulfur colloid on the morning of surgery or 0.5 mCi (18.5 MBq) the day before. With this protocol, which allows for radioactive decay (the half-life of Tc99m is 6 hours) we have observed equivalent results with sameday or day-before isotope (41). It appears that the performance of unltered and ltered isotope preparations is similar. We inject the isotope in a volume of 0.05 cc; this has the advantage of leaving a very small hot spot on the breast, so as not to overshadow the axilla in patients with upper outer quadrant tumors. We inject intradermally at a single site over the tumor, and have found that this technique is superior to parenchymal or peritumoral injection (42), a result that has been independently conrmed in a randomized trial by Povoski et al. (43). In the large multicenter Louisville Sentinel Node Trial (44), supercial injections (intradermal, subdermal, or subareolar) were also more successful than parenchymal (peritumoral) injection or dye-only techniques, and the false-negative rate of all methods was similar, suggesting that the lymphatics of the entire breast usually drain to the same few SLN. Preoperative lymphoscintigraphy (LSG) is essential in SLN biopsy for melanoma, but its role in breast cancer is uncertain. Our practice is to take a single LSG image 30 to 120 minutes after isotope injection. LSG does not improve the identication of axillary SLN (45), other than to alert the surgeon that more than one axillary SLN is present. Even when the LSG is negative, the much more sensitive hand-held gamma probe will identify hot SLN at surgery in most patients (38). LSG demonstrates nonaxillary lymphatic drainage (primarily to the internal mammary nodes) in about 25% of patients (46,47), but the

TECHNIQUE OF SENTINEL LYMPH NODE BIOPSY


For those institutions wishing to start a SLN biopsy program, there are several guiding principles. First, SLN biopsy requires close collaboration among the disciplines of nuclear medicine, surgery, and pathology. Second, SLN biopsy should be done according to a well-dened and consistently applied protocol (36). Third, SLN biopsy is best learned in a formalized course, with experienced mentorship for ones rst procedures. Early on, SLN biopsy should be validated by a backup ALND to allow an audit of both the success rate (which should exceed 90%) and the false-negative rate (which should not exceed 5% to 10%). There is a learning curve for SLN biopsy, but it remains unclear how many backup ALNDs are required before one can perform SLN biopsy on ones own. Convincing data from the Axillary Lymphatic Mapping Against Nodal Axillary Clearance (ALMANAC) trial show that for experienced surgeons working within a well-defined protocol, most failed and/or false-negative procedures occur within a surgeons first few cases (37).

Chapter 9 Sentinel Node Biopsy and Axillary Dissection

109

impact of this information on treatment is minimal and its effect on local control or survival is unproved. SURGERY SLN biopsy is a deceptively simple operation. The following reect my experience (and that of my colleagues) at Memorial Sloan-Kettering Cancer Center (MSKCC) with more than 13,000 procedures. We perform SLN biopsy under general anesthesia for patients having mastectomy and under local anesthetic with intravenous (IV) sedation for breast conservation. Several minutes before starting surgery, we inject 1 to 5 cc of isosulfan blue dye subdermally in the breast, typically at a single site over the tumor, just superolateral to a biopsy scar or just adjacent to a localizing wire. Care is taken not to inject into a prior biopsy cavity, into the retromammary fascial plane, or into the dermis (to avoid tattooing) and to inject a smaller volume of dye for tumors in the axillary tail (to avoid direct spillage into the axilla). Giuliano et al. (18) recommended massage of the injection site to improve lymphatic uptake, but there are no data to support this practice. Using a handheld gamma probe, we identify the isotope injection site in the breast, any focal hot spots in the axilla, and any intervening hot spots that might suggest the presence of intramammary SLN. The axilla is usually explored for SLN through a separate transverse skin line incision prior to the planned mastectomy or breast conservation procedure. When the probability of SLN metastasis is very low (i.e., in mastectomy for DCIS or prophylaxis), SLN biopsy is easily done through the mastectomy incision once the breast has been reected off the chest wall. For mastectomy done through a single oblique incision, SLN biopsy is best done through the axillary end of the incision prior to proceeding with the mastectomy. We prefer to perform SLN biopsy under direct vision and with adequate exposure; the inadvertent division of sensory nerves that accounts for much of the reported morbidity of SLN biopsy can usually be avoided. As dissection is deepened through the axillary fascia, any blue lymphatics are left intact and traced proximally into the axilla, blue nodes are identied, and the gamma probe is used to identify any hot nodes. SLN are usually found low in level I, but in about 25% of cases they are found at other locations: posteriorly along the latissimus muscle, higher in the axilla near the axillary vein, beneath the pectoralis minor in levels II to III, and (much less often) as interpectoral (Rotters) or intramammary SLN. The gamma probe is very useful throughout this dissection and is indispensable in patients with a very large or fatty axilla when blue lymphatics or nodes are not found. All blue SLN and hot SLN are removed, noting for each SLN whether it is blue and/or hot, and taking 10-second isotope counts ex vivo. Most SLN are both blue and hot, but about 10% are found only by dye or by isotope. We submit a median of two to three SLN per patient. When multiple hot SLN (or a diffusely hot axilla) are found, we make every effort to remove the SLN with the highest counts, having found that the hottest SLN is the positive SLN in 80% of cases (48), and we do not in general submit large numbers of SLN, having found that 98% of positive SLN are identied within the rst three SLN and 99% within the rst four SLN submitted (49). Another useful guideline is the 10% rule (50), in which all nodes with counts 10% of the hottest node are submitted as SLN. Nodes that after excision are neither blue nor hot are submitted routinely as nonsentinel nodes. A nal and critical element in SLN biopsy is careful palpation of the axilla and the submission for examination of any

palpably suspicious nodes. In our initial experience with SLN biopsy, we found that a false-negative rate of 14% dening the SLN as blue and/or hot was reduced to 4.6% by dening the SLN as blue and/or hot and/or palpable (48). We usually perform SLN frozen section (FS) during surgery. If positive, FS allows an immediate ALND, and we have found that the yield (FS positive/FS done) and sensitivity (FS positive/SLN positive) of FS are 21% and 61%, respectively (51). We also perform ALND for 2% of patients in whom SLN mapping is attempted and fails [failure is more likely with increasing age and body mass index (52)] or when the axilla remains suspicious to palpation despite a negative FS of SLN and/or non-SLN. The axillary incision after SLN biopsy is closed routinely, without drainage. The morbidity of SLN biopsy is less than that of ALND but is not zero; patients may experience pain, seroma, hematoma, or infection. Blue dye may cause transient bluishgreen discoloration of the skin and urine, blue urticaria in 1% of patients, and anaphylactic reactions in 0.5% of patients (53). A faint blue stain may persist at the breast injection site(s) as long as 1 year postoperatively. PATHOLOGY SLN biopsy is a targeted examination of those few axillary nodes most likely to be positive. While this allows additional pathologic study by serial sectioning and/or immunohistochemical (IHC) stains for cytokeratins, there is no standardized protocol for the pathologic examination of SLN. Recommendations range from routine examination by a single hematoxylin and eosin (H&E)stained section to an exhaustive intraoperative examination of the entire node entailing 30 to 40 sections (54). Our protocol aims to go beyond routine examination but in a way that would be logistically feasible in our high-volume practice. After a negative intraoperative FS, the frozen tissue is thawed, xed, and examined with H&E as a frozen section control; the remainder of the SLN is xed, and two adjacent 5-m sections (one stained with H&E and one with IHC) are taken from each of two levels 50 m apart, generating a total of ve slides per SLN. We have applied this protocol to archival specimens from 368 node-negative patients treated at MSKCC (1976 to 1978) and found occult nodal metastases in 23%. At 20 years follow-up these micrometastases had prognostic signicance whether they were detected by IHC or H&E and whether they were categorized as pN0i (0.2 mm in size) or pN1mi (0.2 to 2 mm in size) by the current American Joint Committee on Cancer staging system (55).

CASE SELECTION FOR AXILLARY LYMPH NODE DISSECTION


In the simplest sense, ALND would seem to be indicated for any patient with a contraindication to SLN biopsy. In fact, as noted above, most of the contraindications to SLN biopsy have been disproved, and SLN biopsy is suitable for virtually all patients with clinical stage T13 N0 invasive cancers (56). While the role of ALND has diminished in the era of SLN biopsy, there are at least nine clear indications for performing it (Table 9.1). A POSITIVE AXILLA Patients with proven axillary node metastases require ALND. Axillary ultrasound (US) and US-guided ne needle aspiration

110

Section I Oncology and Oncoplastic Surgery

(FNA) play a growing role in the diagnosis of axillary node metastasis prior to surgery, and these patients can proceed directly to ALND without SLN biopsy. The results of US-guided FNA vary widely, but even among patients with unselected clinically node-negative (cN0) breast cancers US-guided FNA identied node metastases in 8% of all patients and 21% of node-positive patients (5765). The clinically positive (cN1) axilla is not an indication for ALND; in the era of ALND, clinical axillary examination was equally subject to false-negative and false-positive results (66), and this is confirmed by our experience with SLN biopsy, in which 25% of patients with cN1 axillae proved to be benign (67). PRIOR INADEQUATE AXILLARY LYMPH NODE DISSECTION What is an inadequate (or an adequate) ALND? In the NSABP B-04 trial, Fisher et al. (66) found that the proportion of cN0 patients with positive axillae was the same whether 3 to 5, 6 to 10, 11 to 15, or 16 to 20 nodes had been removed (i.e., the removal of relatively few nodes was sufcient to establish whether the axilla was positive or negative), but that the proportion with 4 nodes positive was highest when 26 nodes had been removed (i.e., a more complete node dissection was necessary to correctly determine the degree of node involvement). They also observed no cases of subsequent axillary LR when six or more nodes had been removed. The apparent adequacy of ALND is multifactorial. First, while the operative technique is well dened, the performance of ALND in practice varies widely. Second, there is wide variation in the thoroughness with which pathologists examine the ALND specimen. Finally, in a small minority of patients very few nodes will be found despite an anatomically correct ALND and a thorough pathologic assessment. For those patients who have had a recent ALND in which (a) the anatomic extent of surgery cannot be documented, (b) the gross specimen is not available for reexamination, (c) few nodes have been removed, and (d) most are positive (raising concern about residual gross axillary disease), it is quite reasonable to perform a completion ALND or to consider axillary RT. A POSITIVE SENTINEL LYMPH NODE BIOPSY ALND is standard care for patients with a positive SLN, especially those detected on intraoperative assessment. Among patients whose SLN are negative on intraoperative exam but positive on permanent pathology, a majority have disease limited to the SLN, and there is debate over the role of ALND in this setting. The risk of non-SLN involvement is predicted by the same variables that predict lymph node involvement in general (especially tumor size, volume of SLN metastasis, and lymphovascular invasion), and a multivariate nomogram can estimate this risk (68). The rate of isolated axillary local recurrence in selected SLN-positive patients who do not have ALND is low [1.9% in our experience (69)], and further study is required to identify subsets of SLN-positive patients who do not require ALND. Two prospective trials address this issue with randomization of SLNpositive patients to ALND versus observation [American College of Surgeons Oncology Group Z0011 (70)] or to ALND versus axillary RT [European Organisation for Research and Treatment of Cancer After Mapping of the Axilla: Radiotherapy or Surgery (AMAROS) (71)].

VALIDATION TRIALS OF SENTINEL LYMPH NODE BIOPSY SLN biopsy is a diagnostic test for the presence of axillary node metastases and is measured by standard test characteristics: sensitivity, specicity, positive predictive value, negative predictive value, and overall accuracy. These do not require a randomized trial, but they do require that SLN biopsy be validated by an immediate planned backup ALND. In an overview (19) of 69 observational (nonrandomized) studies of SLN biopsy with planned ALND (comprising 8,059 patients) the success and false-negative rates were 96% and 7%, respectively. The UK ALMANAC trial (37) required each of its initial participant surgeons to do 40 SLN procedures validated by an ALND, with threshold success and false-negative rates of 95% and 5%, respectively, prior to entering the randomization phase; they observed a shorter learning curve than expected, with most failed and false-negative results occurring in the very rst procedure. This observation is supported by the NASBP B-32 trial (22), in which a false-negative rate of 9.7% did not signicantly decline with increasing surgeon experience. FAILED SENTINEL LYMPH NODE BIOPSY With increasing experience, the success rate of SLN biopsy approaches but does not equal 100%. For that small fraction of failed SLN biopsy procedures or for a SLN procedure that is technically unsatisfactory in any other way, it is reasonable to perform ALND (72). CLINICALLY SUSPICIOUS NODES AT SENTINEL LYMPH NODE BIOPSY During SLN biopsy, a small proportion of patients will have a marked reactive adenopathy that is grossly indistinguishable from cancer. In this setting, benign intraoperative assessment (frozen section or imprint cytology) may not be completely reassuring, and it is reasonable on the basis of clinical suspicion alone to proceed with ALND (72). NEOADJUVANT CHEMOTHERAPY FOR INFLAMMATORY BREAST CANCER The suitability of SLN biopsy for T2 and T3 breast cancers is well established, and SLN biopsy following neoadjuvant chemotherapy is feasible, as shown in a recent meta-analysis of 24 studies in 1,799 patients, which documents success and false-negative rates of 90% and 8%, respectively (73). In a separate study (74) of 56 patients with axillary node metastases proven by FNA who received neoadjuvant chemotherapy and then had SLN biopsy, 31% had a pathologic complete response, but the false-negative rate of SLN biopsy in the remaining patients was unacceptably high (25%). SLN biopsy is reasonable after neoadjuvant chemotherapy in cN0 patients but should used with caution in the setting of proved node metastases or T4 (inammatory) cancers. UNAVAILABILITY OF SENTINEL LYMPH NODE BIOPSY SLN biopsy is not universally available, especially in developing nations, where the added logistics and cost may prove to be excessive. Since the potential impact of SLN biopsy worldwide is substantial (a signicant proportion of clinically diagnosed

Chapter 9 Sentinel Node Biopsy and Axillary Dissection

111

Figure 9.1. The anatomic boundaries of axillary


lymph node dissection, as seen in a transverse section through the midportion of the axilla, showing the pectoralis major and minor anteriorly, the serratus medially, and the latissimus and subscapularis posteriorly.

breast cancers are still node-negative), the challenge will be to nd ways to minimize the cost of SLN biopsy while maintaining accuracy. Where SLN biopsy is not available, ALND should remain standard care. ISOLATED LOCOREGIONAL RECURRENCE Axillary local recurrence after a negative SLN biopsy is rare and comparable to that after ALND, occurring in 1% of patients (75). Most axillary masses that appear after SLN biopsy are benign, but for those that are proven malignant, ALND is indicated. ALND is also indicated for those patients who relapse in the contralateral axilla and do not have other distant sites of disease.

EXTENT OF PROCEDURE The extent of ALND is formally classied as level I, level I to II, or level I to III (complete ALND). While axillary node metastases usually proceed sequentially from levels I to II to III, a large literature addresses the subject of skip metastases, that is, disease limited to levels II to III, sparing level I, or limited to level III, sparing levels I to II. Since most skip metastases were found in level II (isolated level III disease is rare), many authorities recommended a level I to II ALND as the standard operation. At present, skip metastases are best viewed simply as

TECHNIQUE OF AXILLARY LYMPH NODE DISSECTION


The axillary contents lie within a complex space best described as an eccentrically shaped pyramid. Viewed through a transverse section (Fig. 9.1), the axilla is a triangular space bounded by the chest wall medially, the subscapularis posteriorly, the latissimus posterolaterally, and the pectoralis major and minor muscles anteriorly. Viewed from the front through a coronal section (Fig. 9.2), the triangle is bounded by the axillary vein superiorly, the latissimus laterally, and the chest wall medially. The axillary contents are arbitrarily divided into three levels: Level I lies lateral to, level II lies posterior to, and level III lies medial to the pectoralis minor muscle (Fig. 9.2). Level I comprises the largest volume of axillary tissue and the largest proportion of the axillary nodes (perhaps 70%), with level II comprising perhaps 20% and level III 10% or less. The anatomic distinction between axillary levels I and II is somewhat arbitrary, while level III is more anatomically distinct. Historically, breast cancer prognosis was related to the highest level of axillary node involvement, but since about 1970 the number of positive nodes and not the level has emerged as the prognostically relevant variable.

Figure 9.2. The anatomic extent of axillary lymph node dissection,


with levels I, II, and III designated as lying lateral to, behind, or medial to pectoralis minor muscle, respectively.

112

Section I Oncology and Oncoplastic Surgery

Figure 9.3. Incisions for sentinel


lymph node biopsy and/or axillary lymph node dissection for mastectomy or breast-conserving surgery.

level II or III SLN, receiving drainage directly from the breast. Nothing is being skipped, and these nodes should be readily identied by lymphatic mapping and submitted as SLN. In our practice, ALND (done for the indications listed previously) is usually a level I to II dissection. We add a level III dissection for all patients found at operation to have palpably suspicious nodes in levels II to III or other high-risk features such as T3 or T4 (inammatory) cancers. CHOICE OF INCISION The possible incisions for ALND are either separate from (Figs. 9.3, panels 1, 2, and 4) or contiguous with (Figure 9.3, panels 3 and 5) the incision used for the breast operation. A separate incision is best done transversely, gently curved following a skin line, about two fingerbreadths inferior to the axillary skin crease. It should be of adequate length for exposure but should not extend beyond the pectoral border anteriorly, where it would be visible; extensions, if needed, should be posteriorly. Separate axillary and breast incisions are almost always cosmetically superior to contiguous ones, especially in the setting of skin-sparing mastectomy with immediate reconstruction (Figure 9.3, panel 2) and for patients with upper outer quadrant tumors having breast conservation (Figure 9.3, panel 4), where the temptation to perform a single incision (Figure 9.3, panel 5) is the strongest, but where the tumor may prove to be deceptively far from the axilla, requiring resection of a large volume of intervening tissue. A contiguous incision is perfectly reasonable for patients having mastectomy without reconstruction (Figure 9.3, panel 3) and for patients having breast conservation for tumors very high in the axillary tail (Figure 9.3, panel 5). In either case, SLN biopsy is easily done through the axillary end of the incision prior to proceeding with the breast operation. BEGINNING THE OPERATION For patients with severe comorbidity, ALND can be done under local anesthesia with sedation, but it is best done under general anesthesia. The ipsilateral chest and arm should be prepped, with a sterile sleeve covering the arm to allow changes in position during surgery. The operation is begun with a transverse skin line incision extending from the lateral border of the pectoralis major

back toward the latissimus. An inadequate axillary incision reects poorly on the surgeon and does not reduce morbidity, so (within reason) the incision should be adequate for good exposure. FLAP ELEVATION The rst and foremost technical element of ALND is to fully dissect the skin aps to their anatomic limits prior to entering the axilla. This point cannot be emphasized enough: Virtually all technical difficulties with ALND stem from inadequate flap elevation at the outset of the procedure. The second key technical element of ALND is to have adequate countertraction at all times (tissue under tension, surgeon at ease). As the ap dissection deepens, Richardson retractors are placed at each end of the eld and traction constantly applied parallel to the line of dissection. Flap thickness should be uniform and depends on the patients body habitus. For thin patients, I dissect in the areolar plane just beneath the axillary sweat glands, but otherwise I leave 2 to 5 mm of fatty tissue on the ap. Ectopic axillary breast tissue, often visible as a bulge preoperatively, should be encompassed by the skin aps as well. Flaps of uniform thickness will mold smoothly into the axillary defect at the end of the procedure, with a good cosmetic result. The superior ap is elevated to the axillary vein, the medial ap to the pectoralis major and minor, the inferior ap to the serratus anterior, and the lateral ap to the anterior border of the latissimus dorsi. Dissection is carried cephalad along the latissimus to its tendinous portion (the white tendon) and to the axillary vein, which crosses the operative eld anteriorly at about this level. The nal step in ap elevation is to identify the axillary vain superiorly. By retracting the pectoralis major superomedially and the axillary contents inferiorly, the clavipectoral fascia is seen as a at, translucent layer of tissue passing anterior to the axillary vein, artery, and brachial plexus before inserting on the coracobrachialis muscle. As the clavipectoral fascia passes medially it splits to encompass the minor anteriorly and posteriorly before again fusing into a single layer medial to the minor. The clavipectoral fascia is carefully incised just anterior to the axillary vein, and with this step the axillary contents are easily mobilized inferiorly, completely exposing the axillary vein. This step completes the ap elevation and allows the operation to proceed condently with the axillary vein in full view.

Chapter 9 Sentinel Node Biopsy and Axillary Dissection

113

DISSECTION OF THE MEDIAL PECTORAL NERVE The medial pectoral nerve (named for its origin from the medial cord of the brachial plexus) lies lateral to the pectoral muscles, coursing anteriorly and inferiorly as it curls around the lateral borders of the minor and major. It innervates the lower one third of the pectoralis major, should be preserved whenever possible, and if injured causes muscle atrophy, which is strikingly visible after mastectomy, especially with implant breast reconstruction. The accompanying medial pectoral vessels give off small side branches, which pass inferolaterally into the axillary contents, and only after these are carefully ligated and divided can the dissection be deepened beneath the pectoralis minor to reach the level II nodes. At this point, retractors can be placed deep to the pectoralis minor, and by retracting the major, the minor, and the neurovascular bundle medially, level II of the axilla is exposed. Adduction of the arm facilitates this step and will often allow exposure of level III as well. MOBILIZING LEVELS II AND III With levels II and III exposed, the clavipectoral fascia is carefully incised as far medially as possible. Having already incised the clavipectoral fascia superiorly along the axillary vein, this step allows the axillary contents to be mobilized laterally off the chest wall in full view of the axillary vein. Any small side branches of the axillary vein are divided and ligated. If gross axillary disease is palpable in levels II to III and if retraction of the minor provides inadequate exposure, then the pectoralis minor should be divided. This is done by dividing and ligating the medial pectoral neurovascular bundle, bluntly entering the plane between the major and minor, adducting the arm, and retracting the major anteriorly. This step may require the division of one or more small pectoral nerve branches that pass through the body of the minor. The major is retracted anteriorly, exposing and preserving the lateral pectoral nerve and thoracoacromial vessels running along the underside of the major, as well as any interpectoral (Rotters) nodes lying on either side of the neurovascular bundle. Grossly involved Rotters nodes are easily removed at this point. The clavipectoral fascia is incised along the medial border of the minor (taking care to avoid the neurovascular bundle, which also passes medial to the minor), and the minor is then encircled and retracted anteriorly by the surgeons nger. The muscle is divided over the surgeons nger at the level of the axillary vein. This widely exposes levels II and III, and following incision of the clavipectoral fascia superomedially, the entire axillary contents can then be mobilized laterally from Halsteds ligament (the tendinous portion of the subclavius muscle where it inserts on the rst rib, marking the highest extent of level III). In this setting, I prefer to excise the denervated pectoralis minor along with the axillary contents, although the muscle can be left in place. IDENTIFYING THE INTERCOSTOBRACHIAL NERVE As the axillary contents are mobilized laterally off the chest wall, the side branches of the axillary vein are serially divided and ligated. As the dissection proceeds laterally, the intercostobrachial nerve (ICBN, a sensory branch of T2) is encountered running laterally and tethering the axillary contents to the chest wall. I usually sacrice the ICBN, since most often it

will already have been divided laterally in the axilla during the dissection up the anterior border of the latissimus to the axillary vein. It remains unclear whether nerve preservation reduces sensory morbidity, as the consequent loss of skin sensation to the upper inner arm usually resolves within 1 to 2 years. Division of the intercostobrachial nerve frees up the axillary contents further and allows exposure of the long thoracic nerve (which always lies posterior to the intercostobrachial nerve). The T3 and (if necessary) T4 sensory nerve roots are similarly divided to further free the axillary contents from the lateral chest wall. IDENTIFYING THE LONG THORACIC NERVE As the dissection continues laterally, the largest side branch of the axillary vein (thoracoepigastric) is divided and ligated. As the axillary contents are retracted laterally to look for the long thoracic nerve, the rst white line one sees is usually a thin fold of fascia enclosing the serratus muscle and not the nerve. The long thoracic nerve is usually visible lateral to this, running just beneath the thin layer of fascia encompassing the medial aspect of the axillary contents. After carefully incising this layer, the nerve is easily separated from the axillary contents by placing both index ngers into the space just lateral to the nerve and simultaneously sweeping superiorly and inferiorly. This frees and exposes the nerve along most of its length and prevents injury later on. IDENTIFYING THE THORACODORSAL NERVE Most side branches of the axillary vein, including the thoracoepigastric, enter the vein along roughly the same plane. In contrast, the thoracodorsal neurovascular bundle is angulated about 45 degrees posteriorly. Once all of the anteriorly located side branches have been ligated, the thoracodorsal neurovascular bundle is identied by simply retracting the axillary contents inferiorly. The thoracodorsal nerve is easily identied, lying just medial to the artery and vein, by sweeping a nger inferiorly along, and just medial to, the thoracodorsal bundle. COMPLETING THE AXILLARY DISSECTION This intervening bridge of level I tissue is then clamped as close to the vein as possible, divided distal to the clamp, and ligated proximally. The clamp should be applied carefully, with the axillary vein and both nerves under direct vision at all times. If the long thoracic nerve has not been swept completely free of the axillary tissue at this level or if the thoracodorsal nerve is crossing the axilla diagonally and has not been fully exposed, then either nerve could easily sneak into the clamp and be cut during this maneuver. Once the bridge of tissue has been cut, the specimen is swept inferiorly, exposing the subscapularis muscle posteriorly and leaving a clean operative field between the two nerves. As the axillary contents are mobilized inferolaterally, dissection is carried directly along the thoracodorsal nerve, and the small side branches of the thoracodorsal vessels are easily identied and ligated. As the thoracodorsal bundle begins to curve back toward the chest wall, the operation is completed by dividing the few remaining soft tissue attachments inferolateral to the bundle and removing the specimen. For level I to II and level I to III dissections, I orient the specimen with metal tags indicating each anatomic level before handing it off.

114

Section I Oncology and Oncoplastic Surgery

Figure 9.4. The operative eld of a completed axillary lymph


node dissection (ALND). The ligated side branches of the axillary vein lie superiorly, the side branches of the thoracodorsal bundle laterally, and the cut stumps of the intercostobrachial (T2), T3, and T4 sensory nerves medially. Not every ALND will require the sacrice of the intercostal sensory nerves, and depending on the patients anatomy, some or even all of them can be preserved.

CLOSING Figure 9.4 shows the eld of the completed ALND. The axillary vein (with its ligated side branches) is visible superiorly, the cut ends of the T2 (intercostobrachial), T3, and T4 sensory nerves are visible medially, and the long thoracic nerve and the thoracodorsal neurovascular bundle (with its ligated side branches) are seen posteriorly. After inspecting the eld for hemostasis, a at 7-mm Jackson-Pratt drain is placed through a stab wound in the lower skin flap and the skin incision is closed and conrmed to be air-tight by applying suction to the drain. A dressing of gauze, uffs, and surgical bra is applied, and the patient is awakened and returned to the recovery room. POSTOPERATIVE CARE Patients having ALND with breast conservation are normally discharged the following day and those with mastectomy on the second postoperative day. All patients are instructed in wound care (I normally allow showering the day after surgery), given a log book to record their wound drainage (the drains are removed when 24-hour drainage is less than 30 cc), and given a program of postoperative shoulder exercises (which they can usually begin immediately except in the setting of breast reconstruction).

the literature there is wide variation in the denition of lymphedema, methods of assessment, patient characteristics, extent of surgery, extent of RT, and length of follow-up. In a classic 1986 report, Kissin et al. (76) found that (a) lymphedema was more frequent when measured by arm volume (25.5%) than by patient self-assessment (14%), (b) the frequency of subjective late lymphedema was similar for axillary RT alone (8.3%), axillary sampling plus RT (9.1%), and ALND (7.4%), and (c) lymphedema occurred far more often after ALND plus RT (38%, p 0.001). In a comprehensive 2001 overview, Erickson et al. (77) cited ten more recent studies (1991 to 2000) in which the incidence of lymphedema ranged from 2% to 43% and appeared to increase with patient age, body mass index, and length of follow-up. The most useful current data regarding lymphedema will come from the randomized trials that compare SLN biopsy with ALND, three of which report less arm swelling with SLN biopsy (20,21,23). In the ALMANAC trial (21), the patientreported incidence at 12 months of moderate or severe lymphedema was less with SLN biopsy than with ALND (5% vs. 13%), and the relative risk of any lymphedema (for SLN biopsy relative to ALND) was 0.37 (95% condence interval [CI] 0.23 to 0.60). Regarding lymphedema and all of the other side effects of ALND, it is worth noting that the sequelae of ALND are not as severe as patients may expect, and that the sequelae of SLN biopsy may exceed expectations. In a recent report from the prospective ACOSOG Z0010 trial (24) (comprising 5,327 patients), lymphedema developed following SLN biopsy in 6.9% of patients at 6 months; at a median of 5 years follow-up, we have observed lymphedema in 5% of own patients following SLN biopsy and in 16% following ALND (78). Standard recommendations to patients for the prevention of lymphedema include the avoidance of (a) trauma/injury, (b) infection, (c) arm constriction (especially by blood pressure cuffs), and (d) heavy lifting or repetitive motions (77). These recommendations are deeply entrenched in the medical and nursing literature, but there is no evidence that any of them are effective in avoiding lymphedema or that lymphedema can be avoided; they may even have the unintended consequence of making a patient feel that the lymphedema is her fault rather than a known side effect of treatment. Lymphedema cannot be cured, but it can be treated. Using various combinations of elastic compression garments, compression pumps, bandaging, exercise, and complex physiotherapy, 15 studies (1989 to 1991) (77) reported reductions of 15% to 75% in arm volume or circumference. Large randomized studies are needed to determine the relative efcacy of these treatments and the natural history of lymphedema posttreatment. AXILLARY WEB SYNDROME Axillary web syndrome (AWS) was long observed by surgeons but was only named and described by Moskovitz et al. (79) in 2001. AWS is a characterized by the appearance 1 to 8 weeks after ALND (or SLN biopsy) of a network (web) of tender subcutaneous cords running from the lateral axilla down the upper inner aspect of the arm, associated with pain and limitation of arm movement. Among 750 consecutive patients, they observed AWS in 6%. The presumed causesurgical disruption of veins or lymphatics proximally at the level of the axillais supported by the observation of thrombosis in subcutaneous veins and/or lymphatics in 4 of their patients who underwent biopsy. AWS is a benign and self-limited condition that should not be confused with lymphedema and does not require treatment.

COMPLICATIONS OF SENTINEL LYMPH NODE BIOPSY AND AXILLARY LYMPH NODE DISSECTION
LYMPHEDEMA Lymphedema is the single complication of greatest concern to patients and is the subject of an extensive but problematic literature. There are no large population-based studies from the era of ALND that estimate the incidence of lymphedema, and across

Chapter 9 Sentinel Node Biopsy and Axillary Dissection

115

SENSORY MORBIDITY The sensory sequelae of both SLN biopsy and ALND are largely related to the division of sensory nerves, most notably the ICBN, a cutaneous sensory branch of T2 that innervates the upper inner arm, axilla, and superolateral breast. Technical modications of ALND that allow preservation of the ICBN are the subject of an enthusiastic but anecdotal literature. In the single randomized trial comparing ICBN preservation versus division (80,81), ICBN preservation reduced the size of the sensory decit, but there were otherwise no differences between groups in pain, shoulder movement, arm circumference, or presence of neuromas at 3 months or 3 years of follow-up. Of the randomized trials, three report less sensory morbidity with SLN biopsy than with ALND (20,21,23). In the ALMANAC trial (21), the patient-reported incidence of sensory loss at 12 months was less with SLN biopsy than with ALND (11% vs. 31%) and the relative risk of sensory decit (for SLN biopsy relative to ALND) was 0.37 (95% CI 0.27 to 0.50). This and other studies (82) document that the sensory morbidity of ALND diminishes signicantly over time and requires no treatment. SHOULDER FUNCTION Restriction in shoulder range of motion (ROM) is a side effect of ALND, and of the randomized trials, two (20,21) report less limitation in ROM after SLN biopsy than after ALND. In the ALMANAC trial (21), this difference was signicant at 1 month, but shoulder ROM (exion and abduction) improved rapidly in both groups, and at longer follow-up the difference was no longer signicant. Exercises to restore shoulder ROM are an essential element of postoperative care following ALND. INFECTION Cellulitis of the arm, chest wall, or breast is a well-recognized but relatively infrequent side effect of ALND and presumably reflects a localized immune impairment from the surgery. The incidence of cellulitis is unknown, but in a careful report by Roses et al. (83) of 200 patients followed 1 or more years after ALND, 5.5% developed cellulitis and 2% had multiple episodes. Cellulitis can arise following a nonsterile skin break (cut, abrasion, or burn) but often appears without an obvious cause. Patients are routinely advised following ALND to avoid injections, venipunctures, or IVs in the ipsilateral arm, but there is no evidence whatever that sterile skin punctures cause cellulitis or that avoidance prevents either infection or lymphedema (77). Repeated episodes of infection are thought to increase the risk of lymphedema (although it remains unclear in this setting whether infection is a cause or an effect of lymphedema), and prompt treatment with oral or IV antibiotics is recommended.

and predictive powers of gene expression proling prove superior to those of conventional histopathology and if new classes of drugs with curative potential emerge, then ALND, lymph node staging, and breast cancer surgery in general could become obsolete. The present reality is that surgery remains the most effective treatment for breast cancer, lymph node staging remains essential for prognostication, and ALND still has a role in achieving local control for most (if not all) nodepositive patients.

EDITORIAL COMMENTS Dr. Cody, in an eloquent and succinct style, gives us an excellent review of the voluminous literature that addresses the staging of the axilla. As he so aptly points out, the prognostic information gained from lymph node staging is essential to guide adjuvant treatment decisions. Sentinel node biopsy is a robust procedure and has proven to be accurate even with a wide variety of techniques and clinical situations. The number of putative contraindications to it has been gradually decreasing since its accuracy has been demonstrated in almost all scenarios. Controversy still exists about the timing of sentinel node biopsy in the neoadjuvant setting in clinically node negative patients and its accuracy after chemotherapy in node-positive patients. ACOSOG 1071 was opened in late 2009 to evaluate the role of sentinel lymph node surgery and axillary lymph node dissection following preoperative chemotherapy in women with node positive breast cancer (T14 N12 M0) at initial diagnosis. The description of the technical aspects of an axillary dissection is thorough and educational. I will elaborate on a few differences between my usual practice and Dr. Codys. I make every effort to preserve the intercostobrachial nerve(s), unless there is nerve encasement by involved lymph nodes. Preservation of the nerve(s) can make the dissection tedious and requires splitting the axillary contents anteriorly along the length of the nerve. I have found, however, that the numbness caused by sacricing the nerve(s) is bothersome to patients, even if it resolves in a matter of years. I do not tag the different levels of the axilla. This practice was considered mandatory in the presentinel node era at a time when it was thought that the level of lymph node involvement was prognostically important as a sign of skip metastases. We now know that there are not skip metastases, merely different drainage pathways that can be identied with sentinel node mapping. I do, however, in the setting of grossly evident and extensive lymph node metastases, send the highest lymph node, labeled as such, as a separate specimen to pathology. I mark the location of this lymph node in the body with a distinct metal clip. The radiation oncologists I work with have found both of these maneuvers to be useful for radiation treatment planning. There is no consensus in the literature about the use of a closed suction drain after an axillary lymph node dissection. Placement of a drain remains the individual surgeons choice. I tend to avoid drain placement in the majority of patients. I thank Dr. Cody for sharing his knowledge and expertise about axillary staging in such a readable and comprehensive chapter. S.C.W.

AXILLARY STAGING: FUTURE DIRECTIONS


We have entered a dynamic new era in which genomic technologies (a) suggest a new classication of breast cancer (84), (b) appear to improve prognostication (8587), (c) may better predict which patients will (or will not) benet from adjuvant systemic therapy (88), and (d) promise the identication of new therapeutic targets and more effective drugs. If the prognostic

116

Section I Oncology and Oncoplastic Surgery


35. Rodriguez FJ, Martella S, Triro G, et al. Sentinel node biopsy in patients with previous breast aesthetic surgery. Ann Surg Oncol 2009;16:989992. 36. Cox CE, Pendas S, Cox JM, et al. Guidelines for sentinel node biopsy and lymphatic mapping of patients with breast cancer. Ann Surg 1998;5:645653. 37. Clarke D, Newcombe RG, Mansel RE. The learning curve in sentinel node biopsy: the ALMANAC experience. Ann Surg Oncol 2004;11:211S215S. 38. Cody HS, Fey J, Akhurst T, et al. Complementarity of blue dye and isotope in sentinel node localization for breast cancer: univariate and multivariate analysis of 966 procedures. Ann Surg Oncol 2001;8:1319. 39. McMasters KM, Tuttle TM, Carlson DJ, et al. Sentinel lymph node biopsy for breast cancer: a suitable alternative to routine axillary dissection in multi-institutional practice when optimal technique is used. J Clin Oncol 2000;18:25602566. 40. Derossis AM, Fey J, Yeung H, et al. A trend analysis of the relative value of blue dye and isotope localization in 2000 consecutive cases of sentinel node biopsy for breast cancer. J Am Coll Surg 2001;193:473478. 41. McCarter MD, Yeung H, Yeh SDJ, et al. Localization of the sentinel node in breast cancer: identical results with same-day and day-before isotope injection. Ann Surg Oncol 2001;8:682686. 42. Linehan DC, Hill ADK, Akhurst T, et al. Intradermal radiocolloid and intraparenchymal blue dye injection optimize sentinel node identication in breast cancer patients. Ann Surg Oncol 1999;6:450454. 43. Povoski SP, Olsen JO, Young DC, et al. Prospective randomized clinical trial comparing intradermal, intraparenchymal, and subareolar injection routes for sentinel lymph node mapping and biopsy in breast cancer. Ann Surg Oncol 2006;13:14121421. 44. Chagpar A, Martin RC III, Chao C, et al. Validation of subareolar and periareolar injection techniques for breast sentinel lymph node biopsy. Arch Surg 2004;139:614618. 45. McMasters KM, Wong SL, Tuttle TM, et al. Preoperative lymphoscintigraphy for breast cancer does not improve the ability to identify axillary sentinel lymph nodes. Ann Surg 2000;231: 724731. 46. Estourgie SH, Nieweg OE, Olmos RA, et al. Lymphatic drainage patterns from the breast. Ann Surg 2004;239:232237. 47. Heuts EM, Van der Ent FWC, von Meyenfeldt MF, et al. Internal mammary lymph drainage and sentinel node biopsy in breast cancer: A study on 1008 patients. Eur J Surg Oncol 2009;35:252257. 48. Martin RCG, Fey J, Yeung H, et al. Highest isotope count does not predict sentinel node positivity in all breast cancer patients. Ann Surg Oncol 2001;8:592597. 49. McCarter MD, Yeung H, Fey J, et al. The breast cancer patient with multiple sentinel nodes: when to stop? J Am Coll Surg 2001;192:692697. 50. Martin RC, Edwards MJ, Wong SL, et al. Practical guidelines for optimal gamma probe detection of sentinel lymph nodes in breast cancer: results of a multi-institutional study. Surgery. 2000;128:139144. 51. Chan SW, Lavigne KA, Port ER, et al. Does the benet of sentinel node frozen section vary between patients with invasive duct, invasive lobular, and favorable histologic subtypes of breast cancer? Ann Surg 2008;247:143149. 52. Derossis AM, Fey JV, Cody HS III, et al. Obesity inuences outcome of sentinel lymph node biopsy in early-stage breast cancer. J Am Coll Surg 2003;197:896901. 53. Montgomery LL, Thorne AC, Van Zee KJ, et al. Isosulfan blue dye reactions during sentinel lymph node mapping for breast cancer. Anesth Analg 2002;95:385388. 54. Viale G, DellOrto P, Biasi MO, et al. Comparative evaluation of an extensive histopathologic examination and a real-time reverse-transcription-polymerase chain reaction assay for mammaglobin and cytokeratin 19 on axillary sentinel lymph nodes of breast carcinoma patients. Ann Surg 2008;247:136142. 55. Greene FL, Page DL, Fleming ID, et al. Breast. In: Greene FL, Page DL, Fleming ID, et al., eds. AJCC Cancer Staging Manual. New York: Springer; 2002:221240. 56. Cody HS III. Sentinel lymph node biopsy for breast cancer: indications, contraindications, and new directions. J Surg Oncol 2007;95:440442. 57. Bonnema J, van Geel AN, van Ooijen B, et al. Ultrasound-guided aspiration biopsy for detection of nonpalpable axillary node metastases in breast cancer patients: new diagnostic method. World J Surg 1997;21:270274. 58. Damera A, Evans AJ, Cornford EJ, et al. Diagnosis of axillary nodal metastases by ultrasoundguided core biopsy in primary operable breast cancer. Br J Cancer 2003;89:13101313. 59. de Kanter AY, van Eijck CH, van Geel AN, et al. Multicentre study of ultrasonographically guided axillary node biopsy in patients with breast cancer. Br J Surg 1999;86:14591462. 60. Deurloo EE, Tanis PJ, Gilhuijs KG, et al. Reduction in the number of sentinel lymph node procedures by preoperative ultrasonography of the axilla in breast cancer. Eur J Cancer 2003;39:10681073. 61. Krishnamurthy S, Sneige N, Bedi DG, et al. Role of ultrasound-guided ne-needle aspiration of indeterminate and suspicious axillary lymph nodes in the initial staging of breast carcinoma. Cancer 2002;95:982988. 62. Vaidya JS, Vyas JJ, Thakur MH, et al. Role of ultrasonography to detect axillary node involvement in operable breast cancer. Eur J Surg Oncol 1996;22:140143. 63. Verbanck J, Vandewiele I, De Winter H, et al. Value of axillary ultrasonography and sonographically guided puncture of axillary nodes: a prospective study in 144 consecutive patients. J Clin Ultrasound 1997;25:5356. 64. Yang WT, Ahuja A, Tang A, et al. High resolution sonographic detection of axillary lymph node metastases in breast cancer. J Ultrasound Med 1996;15:241246. 65. van Rijk MC, Deurloo EE, Nieweg OE, et al. Ultrasonography and ne-needle aspiration cytology can spare breast cancer patients unnecessary sentinel lymph node biopsy. Ann Surg Oncol 2006;13:3135. 66. Fisher B, Wolmark N, Banes M. The accuracy of clinical nodal staging and of limited axillary dissection as a determinant of histologic nodal status in carcinoma of the breast. Gynecol Obstet 1981;152:765772. 67. Specht MC, Fey JV, Borgen PI, et al. Is the clinically positive axilla in breast cancer really a contraindication to sentinel lymph node biopsy? J Am Coll Surg 2005;200:1014.

REFERENCES
1. Power SD. The history of the amputation of the breast to 1904. Liverpool Med Chir J 1934;52:4956. 2. Halsted WS. The results of operations for the cure of cancer of the breast performed at the Johns Hopkins Hospital from June 1889 to January 1894. Johns Hopkins Hosp Rep 1894;4: 297350. 3. Halsted WS. The results of radical operations for the cure of carcinoma of the breast. Ann Surg 1907;46:119. 4. Urban JA. Radical excision of the chest wall for mammary cancer. Cancer 1951;4:12631285. 5. Patey DH, Dyson WH. The prognosis of carcinoma of the breast in relation to type of operation performed. Br J Cancer 1948;2:713. 6. Auchincloss H. Signicance of location and number of axillary metastases in carcinoma of the breast: a justication for a conservative operation. Ann Surg 1963;158:3746. 7. Fisher B. Laboratory and clinical research in breast cancer: a personal adventure. Cancer Res 1980;40:38633874. 8. Fisher B, Montague E, Redmond C. Comparison of radical mastectomy with alternative treatments for primary breast cancer: a rst report of results from a prospective randomized clinical trial. Cancer 1977;39:28272839. 9. Fisher B, Redmond C, Fisher E. Ten-year results of a randomized clinical trial comparing radical mastectomy and total mastectomy with or without radiation. New Eng J Surg 1985;312:674681. 10. Fisher B, Jeong JH, Anderson S, et al. Twenty-ve-year follow-up of a randomized trial comparing radical mastectomy, total mastectomy, and total mastectomy followed by irradiation. N Engl J Med 2002;347:567575. 11. Hellman S, Weichselbaum RR. Oligometastases. J Clin Oncol 1995;13:810. 12. Clarke M, Collins R, Darby S, et al. Effects of radiotherapy and of differences in the extent of surgery for early breast cancer on local recurrence and 15-year survival: an overview of the randomised trials. Lancet 2005;366:20872106. 13. Early Breast Cancer Trialists Collaborative Group. Effects of radiotherapy and surgery in early breast cancer: an overview of the randomized trials. N Engl J Med 1995;333:14441455. 14. Early Breast Cancer Trialists Collaborative Group. Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomised trials. Lancet 2005;365:16871717. 15. Cabanas R. An approach for the treatment of penile carcinoma. Cancer 1977;39:456466. 16. Morton DL, Wen DR, Wong JH, et al. Technical details of intraoperative lymphatic mapping for early stage melanoma. Arch Surg 1992;127:392399. 17. Krag DN, Weaver DL, Alex JC, et al. Surgical resection and radiolocalization of the sentinel lymph node in breast cancer using a gamma probe. Surg Oncol 1993;2:335340. 18. Giuliano AE, Kirgan DM, Guenther JM, et al. Lymphatic mapping and sentinel lymphadenectomy for breast cancer. Ann Surg 1994;220:391401. 19. Kim T, Giuliano AE, Lyman GH. Lymphatic mapping and sentinel lymph node biopsy in early-stage breast carcinoma. Cancer 2006;106:416. 20. Veronesi U, Paganelli G, Viale G, et al. A randomized comparison of sentinel-node biopsy with routine axillary dissection in breast cancer. N Engl J Med 2003;349:546553. 21. Mansel RE, Falloweld L, Kissin M, et al. Randomized multicenter trial of sentinel node biopsy versus standard axillary treatment in operable breast cancer: the ALMANAC trial. J Natl Cancer Inst 2006;98:599609. 22. Krag DN, Anderson SJ, Julian TB, et al. Technical outcomes of sentinel-lymph-node resection and conventional axillary-lymph-node dissection in patients with clinically node-negative breast cancer: results from the NSABP B-32 randomised phase III trial. Lancet Oncol 2007;8:881888. 23. Purushotham AD, Upponi S, Klevesath MB, et al. Morbidity after sentinel lymph node biopsy in primary breast cancer: results from a randomized controlled trial. J Clin Oncol 2005;23:43124321. 24. Wilke LG, McCall LM, Posther KE, et al. Surgical complications associated with sentinel lymph node biopsy: results from a prospective international cooperative group trial. Ann Surg Oncol 2006;13:491500. 25. Gill G. Sentinel-lymph-node-based management or routine axillary clearance? One-year outcomes of sentinel node biopsy versus axillary clearance (SNAC): a randomized controlled surgical trial. Ann Surg Oncol 2009;16:266275. 26. Del Bianco P, Zavagno G, Burelli P, et al. Morbidity comparison of sentinel lymph node biopsy versus conventional axillary lymph node dissection for breast cancer patients: results of the Sentinella-GIVOM Italian randomised clinical trial. Eur J Surg Oncol 2008;34:508513. 27. Veronesi U, Paganelli G, Viale G, et al. Sentinel-lymph-node biopsy as a staging procedure in breast cancer: update of a randomised controlled study. Lancet Oncol 2006;7:983990. 28. Turner RR, Ollila DW, Krasne DL, et al. Histologic validation of the sentinel lymph node hypothesis for breast carcinoma. Ann Surg 1997;226:271278. 29. Weaver DL, Krag DN, Ashikaga T, et al. Pathologic analysis of sentinel and nonsentinel lymph nodes in breast carcinoma: a multicenter study. Cancer 2000;88:10991107. 30. Cody HS III. Sentinel lymph node biopsy for breast cancer: does anybody not need one? Ann Surg Oncol 2003;10:11311132. 31. Port ER, Fey J, Gemignani ML, et al. Reoperative sentinel lymph node biopsy: a new option for patients with primary or locally recurrent breast carcinoma. J Am Coll Surg 2002;195: 167172. 32. Port ER, Garcia-Etienne CA, Park J, et al. Reoperative sentinel lymph node biopsy: a new frontier in the management of ipsilateral breast tumor recurrence. Ann Surg Oncol 2007;14(8):22092214. 33. Sado HN, Graf RM, Canan LW, et al. Sentinel lymph node detection and evidence of axillary lymphatic integrity after transaxillary breast augmentation: a prospective study using lymphoscintography. Aesthetic Plast Surg 2008;32:879888. 34. Munhoz AM, Aldrighi C, Ono C, et al. The inuence of subfascial transaxillary breast augmentation in axillary lymphatic drainage patterns and sentinel lymph node detection. Ann Plast Surg 2007;58:141149.

Chapter 9 Sentinel Node Biopsy and Axillary Dissection


68. Van Zee KJ, Manasseh DM, Bevilacqua JL, et al. A nomogram for predicting the likelihood of additional nodal metastases in breast cancer patients with a positive sentinel node biopsy. Ann Surg Oncol 2003;10:11401151. 69. Park J, Fey JV, Naik AM, et al. A declining rate of completion axillary dissection in sentinel lymph node-positive breast cancer patients is associated with the use of a multivariate nomogram. Ann Surg 2007;245:462468. 70. Giuliano AE. Z0011: Study synopsis: a randomized trial of axillary node dissection in women with clinical T1 or T2 N0 M0 breast cancer who have a positive sentinel node. Available at: http:/ /www.acosog.org/studies/synopses/Z0011_Synopsis.pdf. Accessed March 9, 2010. 71. EORTC protocol 1098122023. After Mapping of the Axilla: Radiotherapy or Surgery AMAROS. Available at: http:/ /www.eortc.be/protoc/details.asp?protocol10981. Accessed March 9, 2010. 72. Cody HS, Borgen PI. State-of-the-art approaches to sentinel node biopsy for breast cancer: study design, patient selection, technique, and quality control at Memorial Sloan-Kettering Cancer Center. Surg Oncol 1999;8:8591. 73. Kelly AM, Dwamena B, Cronin P, et al. Breast cancer sentinel node identication and classication after neoadjuvant chemotherapy: systematic review and meta analysis. Acad Radiol 2009;16:551563. 74. Shen J, Gilcrease MZ, Babiera GV, et al. Feasibility and accuracy of sentinel lymph node biopsy after preoperative chemotherapy in breast cancer patients with documented axillary metastases. Cancer 2007;109:12551263. 75. Naik AM, Fey J, Gemignani M, et al. The risk of axillary relapse after sentinel lymph node biopsy for breast cancer is comparable with that of axillary lymph node dissection: a followup study of 4008 procedures. Ann Surg 2004;240:462468. 76. Kissin MW, Querci della Rovere G, Easton D, et al. Risk of lymphoedema following the treatment of breast cancer. Br J Surg 1986;73:580584.

117

77. Erickson VS, Pearson ML, Ganz PA, et al. Arm edema in breast cancer patients. J Natl Cancer Inst 2001;93:96111. 78. McLaughlin SA, Wright MJ, Morris KT, et al. Prevalence of lymphedema in women with breast cancer 5 years after sentinel lymph node biopsy or axillary dissection: patient perceptions and precautionary behaviors. J Clin Oncol 2008;26:52205226. 79. Moskovitz AH, Anderson BO, Yeung RS, et al. Axillary web syndrome after axillary dissection. Am J Surg 2001;181:434439. 80. Abdullah TI, Iddon J, Barr L, et al. Prospective randomized controlled trial of preservation of the intercostobrachial nerve during axillary node clearance for breast cancer. Br J Surg 1998;85:14431445. 81. Freeman SR, Washington SJ, Pritchard T, et al. Long term results of a randomised prospective study of preservation of the intercostobrachial nerve. Eur J Surg Oncol 2003;29:213215. 82. Temple LK, Baron R, Cody HS III, et al. Sensory morbidity after sentinel lymph node biopsy and axillary dissection: a prospective study of 233 women. Ann Surg Oncol 2002;9: 654662. 83. Roses DF, Brooks AD, Harris MN, et al. Complications of level I and II axillary dissection in the treatment of carcinoma of the breast. Ann Surg 1999;230:194201. 84. Perou CM, Sorlie T, Eisen MB, et al. Molecular portraits of human breast tumours. Nature 2000;406:747752. 85. vant Veer LJ, Dai H, van de Vijver MJ, et al. Gene expression proling predicts clinical outcome of breast cancer. Nature 2002;415:530536. 86. van de Vijver MJ, He YD, vant Veer LJ, et al. A gene-expression signature as a predictor of survival in breast cancer. N Engl J Med 2002;347:19992009. 87. Wang Y, Klijn JG, Zhang Y, et al. Gene-expression proles to predict distant metastasis of lymph-node-negative primary breast cancer. Lancet 2005;365:671679. 88. Paik S, Shak S, Tang G, et al. A multigene assay to predict recurrence of tamoxifen-treated, node-negative breast cancer. N Engl J Med 2004;351:28172826.

CHAPTER

10
In 1973, recruitment of patients began at the Milan Cancer Institute to compare radical mastectomy to quadrantectomy. Preliminary data published between 1977 and 1981 showed that survival rates were equal (1). Of the 701 women who entered the trial, 177 died of breast cancer86 in the radical mastectomy group and 91 in the group that received breastconserving therapy. The goal of the surgical technique was to remove the primary carcinoma and a generous amount of surrounding tissue, including skin and muscular fascia. Local recurrences were higher in the group that received breast conservation (Table 10.1 and Fig. 10.1). The highest rate of recurrence was in women 45 years of age or younger. The results showed that the long-term survival of women with early breast cancer who were treated with breast-conserving surgery and postoperative radiotherapy to the ipsilateral breast was identical to women who underwent radical mastectomy (1). The Milan II Trial was designed to compare tumorectomy with axillary dissection and radiation to quadrantectomy with axillary dissection and radiation. A tumorectomy was dened as excision of the tumor with a 2-mm margin of healthy tissue around it (Table 10.2; Fig. 10.2). The overall survival rate was not different in the two groups, but the local recurrence rate in the tumorectomy group (13.3%) was twice that of the quadrantectomy (5.3%) group. Local recurrence was highest in patients with an extensive intraductal component (2). Similarly, in 1971, the National Surgical Adjuvant Breast and Bowel Project (NSABP) initiated the B-4 study, a randomized clinical trial to resolve controversy over the surgical management of breast cancer. The 25-year ndings showed there was no survival difference between the Halsted mastectomy and less extensive surgery. The B-6 trial was then designed to evaluate breast-conserving surgery in women with stage I and II tumors that were less than 4 cm in size. Patients were randomized to lumpectomy alone, lumpectomy with radiation, or total mastectomy. No survival differences were noted among the three groups. The local recurrence rate in patients who underwent lumpectomy without radiation was 39.2% versus 14.3% in the group that received radiation. In the B-6 trial, only women with positive nodes received chemotherapy; now the size of the tumor and other characteristics are taken into account when deciding about chemotherapy, which leads to a greater number of women receiving chemotherapy. The newer chemotherapy regimens are also more effective (3). This also leads to an even lower rate of local recurrence.

Costanza Cocilovo

Breast Conservation: Oncologic Issues


addition to surgery and radiation. At 6 months, mastectomy ($12,987) was cheaper than mastectomy with hormonal treatment or chemotherapy ($14,309), breast conservation plus radiation ($14,963), and breast conservation plus radiation and adjuvant hormonal treatment or chemotherapy ($15,779). At 1 year, the costs were roughly equal. Breast conservation cost was in great part from the use of radiation therapy, whereas in mastectomy it was due to higher inpatient costs. Adjuvant therapy signicantly increased costs regardless of the surgery chosen. By 5 years, the nal cost of mastectomy was higher than that of breast conservation; this was likely due to the added costs of reconstruction, which on average added $9600 and other complications from mastectomy (4). Although there are some differences in cost, these are not enough to justify advocating one form of surgical treatment over another.

FACTORS THAT INFLUENCE CHOICE OF BREAST CONSERVATION VERSUS MASTECTOMY


The choice of which surgical option is best for the patient depends in part on patient preference, tumor characteristics, and the recommendations of the surgeon. Tumor characteristics such as extensive calcications, multicentricity, ability to obtain clear margins, tumor size with respect to breast size, and contraindications to radiation therapy could all preclude or advise against an attempt at breast conservation. Patient choice is often inuenced by the experience of friends or relatives, their perception of what is a better treatment, access to radiation therapy facilities, and how they perceive body image versus a fear of local recurrence. Often patients report that their physicians did not present both options to them (5). Morrow et al. reported a signicant correlation between the use of mastectomy and poor prognostic factors such as nodal status and tumor grade, suggesting that some surgeons may view breast conservation as less aggressive (6,7). This rationale is not necessarily sound; if a patient has a poor prognosis, she is generally more likely to recur systemically rather than locally. Surgeon practice volume has been correlated with the use of breast conservation, suggesting that experience and therapeutic bias may inuence the surgical options offered (8). Continuing physician education and encouraging the use of high-volume centers should continue to decrease this problem.

COST OF BREAST CONSERVATION VERSUS MASTECTOMY


In looking at the costs of treatment, the biggest variable was that women younger than 65 years of age had higher treatment costs than older women. This is likely due to the fact that these women were most likely to receive chemotherapy in

THE USE OF NEOADJUVANT CHEMOTHERAPY AND BREAST CONSERVATION


Tumor size can be decreased by giving preoperative chemotherapy. This gives patients who desire breast conservation an opportunity to have it. In the NSABP B-18 trial, preoperative

118

Chapter 10 Breast Conservation

119

TABLE 10.1
Treatment
Halsted QUART

Milan Trial I
Local Recurrences
7 13

N
349 352

New Ipsilateral Carcinomas


9

Contralateral Carcinomas
24 20

Distant Metastases
76 71

QUART, quadrantectomy, axillary dissection, and radiation therapy.

chemotherapy was shown to decrease tumor size and increase the chances of breast conservation, especially among patients with tumors greater than 5 cm (9). McIntosh et al. reported that in 173 women with large or locally advanced breast cancer who were treated with chemotherapy, 44 (or 25%) underwent breast conservation after preoperative chemotherapy (10). After a mean follow-up of 62 months, 1 (2.3%) of the 44 patients who underwent breast conservation developed a local recurrence, and 9 (7.4%) of 121 who had a mastectomy developed a local recurrence. Patients who had better responses to chemotherapy were offered breast conservation, so there was a selection bias in this study. However, the results demonstrate that with proper patient selection, patients can be offered breast conservation postchemotherapy (10). In 2006, the Milan group published their review of 309 women who were candidates for mastectomy and then underwent neoadjuvant chemotherapy. In this group, 195 patients ended up having breast conservation surgery and 114 a modified radical mastectomy. At a median follow-up of 41 months 13 (6.7%) patients treated with breast conservation had an ipsilateral tumor recurrence. Six (3.1%) patients had a regional relapse, 28 (14.4%) women had distant metastases, and 24 (12.3%) patients had positive margins or margins that were less than 1 mm on their nal pathology report. These patients all received radiation. Cumulative incidence of distant metastases was similar in patients with positive and negative margins, and there was no difference in terms of overall survival (11).

TABLE 10.2

Comparison of the Aims, Types of Incision, Extent of Surgery, and Types of Closure for Tumorectomy and Quadrantectomy
Quadrantectomy
To remove all cancer tissue

A French study by Soucy et al. was aimed specically at comparing surgical margin involvement in breast conservation between those receiving neoadjuvant treatment and those with primary surgical treatment. Risk factors for positive margins have been studied and include age, family history, large tumor size, nodal involvement, presence of lymphovascular invasion, extensive intraductal component, and ductal or lobular extension (13). The authors reported a rate of 21% positive margins in those who underwent neoadjuvant chemotherapy and an 18% rate in the non-neoadjuvant group. Factors related to positive margins included higher nodal stage and larger tumor size, presence of lobular carcinoma, and positive hormonal receptors. Preoperative chemotherapy did not affect margin status. The authors felt that an association between positive hormone receptor status and positive margins remained unexplained. Twenty percent of positive hormonal receptor tumors had positive margins versus 10% for negative hormonal receptor tumors. Hormone receptorpositive tumors respond less to chemotherapy, but this does not explain their higher rates of positive margins overall. Lobular carcinoma had a signicantly higher rate of positive margins, 43% versus 16% in ductal carcinoma. Lobular carcinoma tends to be multicentric and bilateral and more difcult to assess on conventional mammography. It also has a lesser response to neoadjuvant chemotherapy, all of which contribute to the higher rates of positive margins. Therefore, the authors concluded that although regression patterns after neoadjuvant chemotherapy can be variable, breast conservation afterward yields no higher incidence of positive margins than primary surgical treatment of invasive breast cancer (13). The MD Anderson Cancer Center updated their experience of breast conservation after neoadjuvant chemotherapy from 1987 to 2000. There was a median follow-up of 60 months.

Tumorectomy
Aim To remove the bulk of the tumor To improve the efcacy of radiotherapy Mainly circular No skin removed, 1/2 to 1 cm of normal breast tissue around the tumor No reconstruction

Incision Extent

Closure

Radial, to encompass the ductal tree Good portion of skin and muscular fascia, 2 to 3 cm of normal breast tissue from the tumor borders Accurate reconstruction of breast

Figure 10.1. Design of Milan Trial I. CMF, cyclophosphamide, methotrexate, uorouracil; QUART, quadrantectomy, axillary dissection, and radiation therapy.

120

Section I Oncology and Oncoplastic Surgery

Figure 10.2. Design of Milan Trial II, 1985 to 1987.

Local in-breast recurrence for patients with T3 and T4 disease was not different from that of patients with T1 or T2 disease, although locoregional recurrence was higher with larger tumors. Locoregional recurrence was dened as the adjacent nodal basins (supraclavicular fossa, axilla, infraclavicular fossa, and internal mammary nodes). Variables that positively correlated with locoregional and in-breast recurrence were pathologic residual tumor greater than 2 cm, a multifocal pattern of residual disease, and lymphovascular space invasion (14). The American Society of Clinical Oncology (ASCO) gathered an international expert panel to update their recommendations. The decision to recommend neoadjuvant treatment is based on the endocrine responsiveness of the tumor, lymph node status, menopausal status, and tumor size and grade. The type of therapy should be tailored to the patient, and some groups, like that at the MD Anderson Cancer Center, have given postoperative chemotherapy to those patients with residual disease. Large trials demonstrating breast conservation after neoadjuvant endocrine therapy are being done, but smaller trials in older patients have shown good success. Trastuzumab is being given preoperatively only in clinical trials. In terms of local failure rate, it seems safe to perform breast conservation surgery, but an insufcient response may lead to higher local regional recurrence rates. They conclude that the full potential of neoadjuvant chemotherapy has not been exploited, and this is likely true (15). These studies indicate that neoadjuvant chemotherapy can safely expand the number of patients undergoing breast conservation. However, tumor characteristics before treatment and tumor response to chemotherapy need to be taken into account when making a nal decision regarding breast conservation.

IMPACT OF BREAST TUMOR RECURRENCE ON OUTCOME


Many studies report that the long-term impact of local recurrence is low because the overall survival rates between those that have a local recurrence and those that do not are similar. However, this is becoming controversial. The MD Anderson Cancer Center recently reported that ipsilateral breast tumor recurrence was an independent predictor of systemic recurrence and poor disease-specic survival (16). Some studies claim a later peak in distant recurrence, whereas others suggest that local recurrence may be a risk factor but not a cause of distant metastases. Because this question has not yet been answered

denitively, it is best to try to prevent local recurrences (5). There are two types of local recurrences: true local recurrence from cells that were presumably not removed surgically or killed by radiation or adjuvant therapy, and new breast cancer cases arising from residual breast tissue. True recurrences tend to develop more quickly and be closer to the original tumor site (5). A 27-year single-institution review of the MD Anderson data found that the 5-year ipsilateral breast tumor recurrence rate was signicantly lower among patients treated in 1994 to 1996 than among patients treated before 1994 (1.3% vs. 5.7%), largely because of a drop in recurrences among patients who were younger than 50 years of age (1.4% vs. 9.1%). The authors felt this reected four major strategy changes at their institution after 1994. First, the rate of positive or unknown margins had decreased because of the use of intraoperative and postoperative margin analysis. The use of chemotherapy in adjuvant and neoadjuvant settings had increased. Third, the use of tamoxifen by women with hormone receptor cancer has increased in both the premenopausal group and the postmenopausal group. Fourth, the delivery of radiation boost declined from 1994 to 1996. This would seem to be a negative strategy change; however, prior to 1994 the most common indication for using the boost was the presence of close, positive, or unknown margins. Other factors not looked at in this study, such as the continued improvement in diagnostic imaging, will likely also contribute to a decrease in local recurrence (17). In their review of locally recurrent breast cancer after conservation therapy, Huston and Simmons found that the most common type of local recurrence (57% to 88%) was at the site of primary breast cancer and most probably represents incomplete resection of the initial cancer. The second type is within the same quadrant (22% to 28%) but not directly at the site of the initial carcinoma. These are hypothesized to represent the evolution of ductal carcinoma in situ (DCIS) since the time of the initial surgery. The third type is within a different quadrant (10% to 12%) and likely represents a new primary breast cancer. More rarely are radiation induced or an inammatory recurrence. The majority of patients who recur near the original tumor do so within 33 months; those at a more distant location recur on average at 75 months (18). Huston and Simmons believed that the factors associated with increased risk of local recurrence were margin status, extensive intraductal component, patient age, and lack of radiation. The majority of data supports that close or positive surgical margins result in an increased rate of local recurrence. Similarly an extensive intraductal component, if not widely excised, led to an increased risk. Larger resection was associated with a lower risk of recurrence. Patients at a younger age, especially less than 35 years, were found to have higher rates of local recurrence and decreased rates of survival than those in older age groups. The NSABP B-06 and B-17 trials both showed that with radiation local recurrence decreased (18). In all likelihood, local recurrence does affect survival in a small percentage of patients. As the full impact of local recurrence continues to be dened, aggressive primary local treatment should continue to be the standard of care.

RADIATION TREATMENT
As the majority of recurrences occur close to the lumpectomy cavity, the need for whole-breast irradiation versus partial radiation to the lumpectomy cavity has been an area of recent interest.

Chapter 10 Breast Conservation

121

Radiation is a key component of breast conservation therapy. The standard treatment is a 6-week course of external beam treatment. Generally patients who do experience local failure tend to recur in the same quadrant. Pooled results from 15 trials (9,422 patients) reported that the relative risk of local recurrence was three times greater for those not receiving radiotherapy. This resulted in a slight survival benet (19). This suggests that local control is important in improving survival and adds further evidence that tumor recurrences can adversely affect survival by having the capacity to metastasize (20). Recent randomized data suggest that for selected patients a shorter treatment course (16 fractions) and lower overall dose lead to similar local control, toxicity, and cosmetic results (21,22). It has been suggested that in the subgroup of the elderly radiation can be omitted. It may be appropriate to omit if the patient has poor life expectancy or performance status. Otherwise they too will have a higher local recurrence rate (20). This has caused an increased interest in accelerated partial breast radiation. It would reduce treatment time and reduce the irradiated field. This would also increase convenience and decrease toxicity. There are several forms of radiotherapy tumor bed techniques. These techniques include brachytherapy implants, where plastic catheters are loaded with iridium, the insertion of a uid-lled balloon that lls the operative cavity and is then installed with radioactive isotopes, and the use of an electron beam via a mobile linear accelerator or supercial photon x-rays. The advantage of the tumor bed technique is that the device is accurately placed in the tumor bed, ensuring the accurate delivery of radiation. The radiation penetrates several centimeters beyond the surgical cavity. Less breast tissue is irradiated, and large doses can be used. Partial breast radiation generally has a shorter course of treatment, which is helpful in patients who have difculty with access to a radiation center (20). Early data suggest that local control rates and toxicities are similar to those with external beam radiotherapy in selected patients studied. Another relatively new technique is intensity-modulated radiotherapy (IMRT). The use of sophisticated imaging in the radiotherapy planning process has allowed the delivery of a homogenous dose of radiotherapy to the target volume and less dose to surrounding structures, such as the heart and lungs. This is particularly relevant given the three-dimensional shape of the breast, which often makes delivery difcult and inhomogeneous. Because of this IMRT has been embraced more enthusiastically by radiation oncologists treating other sites. The specic challenges of radiating breast cancer patients come from accounting for thoracic movement and the shape of the breast. Currently there are few data available on clinical outcome of IMRT. Sacchini et al. from Memorial Sloan-Kettering reports on 52 women who were treated for early-stage breast cancer with intraoperative radiation therapy, 20 or 18 Gy in a single dose. They were followed for 1 year. Two women required reoperation for poor wound healing. So far no local recurrences have been reported, but long-term outcome is awaited (23). Another aspect to consider is that as chemotherapy regimens become, longer radiation continues to get delayed further. There are no data to suggest that the delay affects outcome, but an accelerated radiation course could begin immediately postoperatively without delaying the start of chemotherapy. Another area of controversy, especially with the interest in more targeted elds, is the question of irradiating nodal areas. The MA.20 trial has been established to address the question of whether there is benet to adding radiation to the supraclavicular

fossa and internal mammary chain when the axillary nodes are involved (20). The overall consensus is that input is needed from long-term clinical data on these new radiotherapy techniques. There needs to be consensus on target volume contouring and dose volume constraints for nontarget tissue (24), as well as consensus on which patients are best served by these new techniques.

DUCTAL CARCINOMA IN SITU AND BREAST CONSERVATION


Similar principles apply to ductal carcinoma in situ as to invasive cancer. Vargas et al. report on 410 cases of DCIS, 367 of which were treated with breast-conserving surgery and 43 with mastectomy. Of the former 367 patients, 313 had radiation therapy (RT), whereas 54 had lumpectomy alone. Follow-up showed that 8.2% experienced an ipsilateral breast recurrenceof these, 8% had RT and 9.3% did notand 4.7% developed a chest wall recurrence after mastectomy. Of these, 80% were felt to be true recurrence as opposed to new primaries. True recurrences were those within or adjacent to the tumor bed. The factors associated with ipsilateral breast recurrence were younger age (45 years), close positive margins (2 mm), no breast radiation, and lower electron boost. These recurrences were found to have a small (4% to 12%) but statistically signicant negative impact on the rate of distant metastasis and cause-specic survival (25).

DETECTION OF LOCAL RECURRENCE


Detection of local recurrences is most often done via mammogram (42% to 75%), as well as by physical examination (10% to 33%) and less often by other imaging techniques. Magnetic resonance imaging becomes most accurate for identication of residual tumor 18 months after cessation of radiation therapy; it takes about that much time for radiation fibrosis to decrease. Some trials involve repeat lumpectomy and local radiation treatment after prior whole-breast radiation, but this is still experimental and should be done only within the scope of a clinical trial. The standard treatment for local recurrence is a mastectomy. Reconstruction can be performed with autologous tissue. Prognosis depends on whether the recurrence is invasive versus noninvasive, size and stage, method of detection, and presence of breast involvement in addition to axilla and skin (18).

BREAST CONSERVATION AND ONCOPLASTIC SURGERY


Breast reconstruction after breast conservation was historically not performed. However, there has been growing interest in the area of breast oncoplastic reconstruction. The most common way to achieve breast reconstruction after breast conservation is through tissue rearrangement within the affected breast and a contralateral symmetry procedure on the other breast. These reconstructions can be performed at the time of the original surgery, but if the patient does not have clear margins, then the patient is either obligated to have a mastectomy or accept the inadequate margins. In our institution, we nd the best approach is to await clear margins and then have the oncoplastic procedure

122

Section I Oncology and Oncoplastic Surgery

and contralateral reduction prior to radiation. Less often, patients do not have enough tissue for tissue rearrangement, and these patients need supplemental tissue. This can be done with a muscle ap but is a more involved surgery. Losken et al. developed a management algorithm for patients who are potential candidates for oncoplastic surgery (26). Breast size in relation to tumor size is the initial criterion. Patients are divided into those who need volume replacement such as a local or distant ap and those who qualify for a volume displacement procedure. The advantage of a one-stage procedure is that it potentially avoids scar formation and brosis and a second trip to the operating room. The main disadvantage of a one-stage procedure is that when there is a positive margin noted on nal pathology report, reexcision of that positive margin post tissue rearrangement may not be accurate, and mastectomy may be necessary. It is most common to have DCIS rather than invasive tumor at the positive margins. In Loskens series, all patients who failed reexcision were under 40 years of age. Because of this, I recommend that patients under 40 years of age with a large DCIS component be managed by a staged procedure (26). There are many oncologic issues involved in breast conservation. The ultimate goal of uncompromised disease-free survival must always be kept in mind while choosing treatments that are equally effective and well or better tolerated by the patient. Avoiding the overtreatment of patients is also important as time and health care resources become scarcer. Attempting to balance the desire of most patients for expedient and appropriate treatment with the best cosmetic outcome that they can achieve is also important.

undergo reoperation to achieve a negative margin status. Evolving technologies for margin assessment in the operating room may decrease the reoperation rate. In situations where intraoperative radiotherapy is used or one-stage oncoplastic surgery is desirable, a method of reliably assuring negative margins intraoperatively would add signicantly to the care of the breast cancer patient. S.C.W.

REFERENCES
1. Veronesi U, Cascinelli N, Mariani L, et al. Twenty-year follow-up of a randomized study comparing breast-conserving surgery with radical mastectomy for early breast cancer. N Engl J Med 2002;347(16):12271232. 2. Veronesi U, Volterrani F, Luini A, et al. Quadrantectomy versus lumpectomy for small size breast cancer. Eur J Cancer 1990;26(6):671673. 3. Fisher B, Anderson S, Bryant J, et al. Twenty-year follow-up of a randomized trial comparing total mastectomy, lumpectomy, and lumpectomy plus irradiation for the treatment of invasive breast cancer. N Engl J Med 2002;347(16):12331241. 4. Barlow WE, Taplin SH, Yoshida CK, et al. Cost comparison of mastectomy versus breastconserving therapy for early-stage breast cancer. J Natl Cancer Inst 2001;93(6):447455. 5. Meric-Bernstam F. Breast conservation in breast cancer: surgical and adjuvant considerations. Curr Opin Obstet Gynecol 2004;16(1):3136. 6. Morrow M, White J, Moughan J, et al. Factors predicting the use of breast-conserving therapy in stage I and II breast carcinoma. J Clin Oncol 2001;19(8):22542262. 7. Morrow M. Rational local therapy for breast cancer. N Engl J Med 2002;347(16):12701271. 8. McKee MD, Cropp MD, Hyland A, et al. Provider case volume and outcome in the evaluation and treatment of patients with mammogram-detected breast carcinoma. Cancer 2002;95(4):704712. 9. Wolmark N, Wang J, Mamounas E, et al. Preoperative chemotherapy in patients with operable breast cancer: nine-year results from National Surgical Adjuvant Breast and Bowel Project B-18. J Natl Cancer Inst Monogr 2001;(30):96102. 10. McIntosh SA, Ogston KN, Payne S, et al. Local recurrence in patients with large and locally advanced breast cancer treated with primary chemotherapy. Am J Surg 2003;185(6): 525531. 11. Gentilini O, Intra M, Gandini S, et al. Ipsilateral breast tumor reappearance in patients treated with conservative surgery after primary chemotherapy. The role of surgical margins on outcome. J Surg Oncol 2006;94(5):375379. 12. Singletary SE. Surgical margins in patients with early-stage breast cancer treated with breast conservation therapy. Am J Surg 2002;184(5):383393. 13. Soucy G, Belanger J, Leblanc G, et al. Surgical margins in breast-conservation operations for invasive carcinoma: does neoadjuvant chemotherapy have an impact? J Am Coll Surg 2008;206(3):11161121. 14. Chen AM, Meric-Bernstam F, Hunt KK, et al. Breast conservation after neoadjuvant chemotherapy: the MD Anderson cancer center experience. J Clin Oncol 2004;22(12): 3032312. 15. Kaufmann M, Hortobagyi GN, Goldhirsch A, et al. Recommendations from an international expert panel on the use of neoadjuvant (primary) systemic treatment of operable breast cancer: an update. J Clin Oncol 2006;24(12):19401949. 16. Meric F, Mirza NQ, Vlastos G, et al. Positive surgical margins and ipsilateral breast tumor recurrence predict disease-specic survival after breast-conserving therapy. Cancer 2003;97(4):926933. 17. Cabioglu N, Hunt KK, Buchholz TA, et al. Improving local control with breast-conserving therapy: a 27-year single-institution experience. Cancer 2005;104(1):2029. 18. Huston TL, Simmons RM. Locally recurrent breast cancer after conservation therapy. Am J Surg 2005;189(2):229235. 19. Vinh-Hung V, Verschraegen C. Breast-conserving surgery with or without radiotherapy: pooled-analysis for risks of ipsilateral breast tumor recurrence and mortality. J Natl Cancer Inst 2004;96(2):115121. 20. Delaney G. Recent advances in the use of radiotherapy to treat early breast cancer. Curr Opin Obstet Gynecol 2005;17(1):2733. 21. Truong MT, Hirsch AE, Formenti SC. Novel approaches to postoperative radiation therapy as part of breast-conserving therapy for early-stage breast cancer. Clin Breast Cancer 2003;4(4):253263. 22. Whelan T, MacKenzie R, Julian J, et al. Randomized trial of breast irradiation schedules after lumpectomy for women with lymph nodenegative breast cancer. J Natl Cancer Inst 2002;94(15):11431150. 23. Sacchini V, Beal K, Goldberg J, et al. Study of quadrant high-dose intraoperative radiation therapy for early-stage breast cancer. Br J Surg 2008;95(9):11051110. 24. Van Limbergen E, Weltens C New trends in radiotherapy for breast cancer. Curr Opin Oncol 2006;18(6):555562. 25. Vargas C, Kestin L, Go N, et al. Factors associated with local recurrence and cause-specic survival in patients with ductal carcinoma in situ of the breast treated with breast-conserving therapy or mastectomy. Int J Radiat Oncol Biol Phys 2005;63(5):15141521. 26. Losken A, Styblo TM, Carlson GW, et al. Management algorithm and outcome evaluation of partial mastectomy defects treated using reduction or mastopexy techniques. Ann Plast Surg 2007;59(3):235242.

EDITORIAL COMMENTS The indications for breast conservation have broadened over the decades that have elapsed since trials rst began in the 1970s. Large tumors, lobular histology, central tumors, positive nodes, and ductal carcinoma in situ are no longer absolute contraindications to breast-conserving surgery. Studies with 25 years of follow-up have veried that survival of patients treated with breast-conserving surgery followed by radiation is equal to that with mastectomy. There is overwhelming data, however, that recurrence rates are higher in patients who have had breast conservation than in those who have had mastectomy, especially if no radiation therapy was given. The evidence that local recurrence has a negative impact on survival is taking longer to accumulate. Patient selection for breast conservation continues to be an important predictor of successful outcomes for local control. All patients who are candidates should be offered breast conservation and counseled about their surgical options. Neoadjuvant therapy and oncoplastic surgery are rendering a greater number of patients as acceptable candidates for breast-conserving surgery and improving cosmetic results, without compromising local control. Attaining clear margins continues to be a vexing problem for surgeons performing breast-conserving surgery. Positive margins occur in up to 35% of patients. As positive margins are predictive of local recurrence, it is unacceptable to tolerate positive margins, and these patients must

CHAPTER

11
INTRODUCTION
Breast conservation surgery (BCS) is an important part of early breast cancer treatment, with a survival outcome comparable to that of radical procedures (1). Recently, increasing attention has been focused on oncoplastic procedures because the reconstructive techniques provide a wider local excision while still achieving the goals of a better breast form (216). Introduced by Audretsch et al. (17,18) in 1998, oncoplastic surgery is a relatively new but increasingly used procedure. It combines principles of oncologic and plastic surgery techniques to obtain oncologically sound and aesthetically pleasing results (2). Despite the acceptance that most BCS can be managed with primary closure, the aesthetic result may be unpredictable and occasionally can be complex to reconstruct (37,9). Thus, by means of customized techniques the surgeon ensures that oncologic principles are not jeopardized while meeting the needs of the patient from an aesthetic point of view. In general, these techniques involve volume displacement or replacement techniques and sometimes include contralateral breast surgery (7). Among the procedures available, local aps, latissimus dorsi myocutaneous ap, and reduction mammaplasty/mastopexy techniques are the most commonly employed (3,4,69). Regardless of the fact that there is no consensus concerning the best approach, the decisive criteria are determined by the surgeons experience and the size of the defect in relation to the size of the remaining breast (69). The main advantages of the technique utilized should include reproducibility, low interference with the oncologic treatment and long-term results. Probably, all these goals are not achieved by any single procedure, and each technique has advantages and limitations (8).

Alexandre Mendona Munhoz

Oncoplastic Surgery: Managing Common and Challenging Problems


(3,57,9). Some studies advocate that the ideal treatment should be preventive by performing immediate reconstruction before radiotherapy (37,9,18,19). Papp et al. (19) observed that the aesthetic results showed a higher success rate in the immediate group when compared with delayed reconstruction patients. Similarly, Kronowitz et al. (6) observed that immediate repair is preferable to delayed repair because of a decreased incidence of complications (Fig. 11.1). In terms of oncologic advantages, immediate reconstruction can be benecial. Some studies have observed that patients with macromastia present more radiation-related complications than patients with normal-volume breasts (16,20,21). In addition, some authors suggested that there is an increased fat content in large breasts, and the fatty tissue results in more brosis after radiotherapy than glandular tissue (22) (Fig. 11.2). Gray et al. (21), in a series of 257 patients, found that there was more retraction and asymmetry in the large-breasted versus the small-breasted group. Thus, breast reduction can increase the eligibility of large-breasted patients for BCS since it can reduce the difculty of providing radiation therapy (7,9,16,20,21). Another aspect is the possibility of accomplishing negative resection margin. In fact, the immediate reconstruction allows for wider local tumor excision, potentially reducing the incidence of margin involvement (3,7,23). Kaur et al. (23) compared patients submitted to oncoplastic procedures and to BCS. The oncoplastic approaches permitted larger resections, with a superior mean volume of the specimen and negative margins. Another positive aspect is the opportunity of examining the opposite breast. Despite the low incidence of occult malignancy observed in aesthetic breast reductions, the risk undoubtedly increases in patients with previous breast cancer (3,7,8,12,24). In our previous study (24), 4.3% of the patients submitted to opposite mammaplasty were diagnosed with breast cancer. Despite the benets, the immediate reconstruction presents limitations. The surgical time can be lengthened, and potential complications can unfavorably affect the aesthetic outcome. It can be time consuming, technically demanding, and require specialist training to learn and properly apply these procedures (2,3,7). Despite these limitations, the immediate approach can reduce deformities, favor the oncologic treatment, and optimize the aesthetic outcome in most early-stage cancer patients.

MANAGING COMMON PROBLEMS


TIMING OF RECONSTRUCTION Oncoplastic reconstruction may begin at the time of BCS (immediate), weeks later (delayed-immediate), or months to years afterward (delayed). Surgical planning and timing of reconstruction should include breast volume, tumor location, and the extent of glandular tissue resected, enabling each patient to receive an individual custom-made reconstruction (8).

Delayed Reconstruction
Some patients are so distressed by their cancer diagnosis that they are not capable of significantly participating in reconstructive considerations, and delayed reconstruction defers decisions about it. Another important point is related to postoperative radiation, which may adversely affect the aesthetic outcome of an immediate BCS reconstruction. One might

Immediate Reconstruction
With immediate reconstruction, the surgical process is smooth because both procedures can be associated in one operative setting. In addition, because there is no scar tissue, breast reshaping is easier, and the cosmetic results are improved

123

Figure 11.1. A, B: A 41-year-old patient with invasive ductal carcinoma (1.9 cm) of the left breast.
C, D: The patient underwent a left superior-lateral quadrantectomy and total axillary dissection, immediately followed by a bilateral superior-medial pedicle reduction mammaplasty reconstruction; a total of 245 g was removed from the left breast and 215 g from the right breast. E, F: Two-month postoperative appearance during radiotherapy. The left breast is more retracted and higher than the right breast. G, H: Eight-month postoperative appearance after the radiotherapy with a very good outcome.

124

Figure 11.2. A, B: A 59-year-old patient with invasive ductal carcinoma (3.9 cm) of the left breast. C, D: The
patient underwent a left superior quadrantectomy and total axillary dissection through the mammaplasty incision, immediately followed by a bilateral inferior pedicle reduction mammaplasty reconstruction; a total of 925 g was removed from the left breast and 1.015 g from the right breast. E, F: Three-month postoperative appearance during the radiotherapy. The left breast is more retracted and higher than the right breast. G, H: Two-year postoperative appearance after the radiotherapy with a very good outcome.

125

126

Section I Oncology and Oncoplastic Surgery

Figure 11.3. A, B: A 51-year-old patient with severe breast asymmetry. Five years previously, the patient
underwent a left superior-lateral quadrantectomy and radiotherapy without reconstruction. C, D: Due to the presence of severe breast asymmetry, the presence of scar tissue, and radiotherapy skin effects, the patient underwent a delayed reconstruction with superior pedicle bilateral reduction mammaplasty. E, F: Two-year postoperative appearance with a very good outcome. A total of 225 g was removed from the left breast and 875 g from the right breast.

Chapter 11 Oncoplastic Surgery

127

surmise that the final contour of the breast cannot be predicted at the time of the BCS. It is well accepted that radiation usually involves some degree of brosis and shrinkage. Some authors observed that although the aesthetic outcome can be satisfactory, the appearance of the radiated breast is occasionally less pleasing than that of the nonradiated one (36,9,12,15,25). Thus, in delayed reconstruction the plastic surgeon waits until the postoperative changes in the deformed breast stabilize (9) (Fig. 11.3). Concerning the delayed reconstruction management, Clough et al. (4) proposed a classication based on response to the type of reconstruction. Patients with a type I breast defect have a normal breast with no deformity. However, there is asymmetry between the contralateral breasts. These patients were reconstructed with contralateral breast surgery (see Fig. 11.3). Type II patients have clearly deformed breasts, and the defect is repaired with ipsilateral breast surgery or ap reconstruction. Type III patients have major deformity and were treated with mastectomy and reconstruction (Fig. 11.4). Another controversy is related to the postoperative recovery. In theory, some complications of the immediate reconstructions can unfavorably defer the adjuvant therapy. With the delayed approach, operative time is shortened and the surgical process is less extensive than in the immediate approach. However, our previous experience (8,1013,24) and that of others (5,26) has shown that immediate reconstruction does not compromise the start of radiotherapy and chemotherapy in the overall treatment of breast cancer.

trends in types of breast defects and to develop an algorithm for immediate BCS reconstruction on the basis of the initial breast volume, the extent/location of glandular tissue resection, and the remaining available breast tissue (8).

Partial Breast Defects Classication

Type I. Defects include tissue resection in smaller breast without ptosis. Type IA defects involve minimal defects that do not cause volume alteration/distortion in the breast shape and the tissue resected is less than 10% to 15% percent of the total breast volume. Initial tumor exposure is achieved through a periareolar approach in cases where the tumor is located deeply. In patients where the tumor is located close to the skin, a separate incision is planned directly over the region to be resected. Type IB defects involve moderate defects that do originate moderate volume alteration/distortion in the breast shape or symmetry and the tissue resected is between 15% and 40% of the total volume. Usually, the skin above the tumor is resected with the tumor. Type IC defects involve large defects that do cause signicant volume distortion and the tissue resected is more than 40% of the total breast volume.

Type II. This group includes tissue resection in medium-sized


breasts with or without ptosis. Type IIA defects are small defects that do not cause enough volume distortion in the breast shape. Type IIB defects are moderate defects that cause minor to moderate volume alteration in the breast shape. Type IIC defects are large defects that cause moderate to large volume variations in the breast shape and symmetry.

Delayed-Immediate Reconstruction
By denition, two-stage procedures can be delayed-immediate, with initial wide local excision and then oncoplastic reconstruction with appropriate technique at that time when the histologic margin assessment has been performed (7,9,27,28). In this approach, it is possible to postpone reconstruction until after the review of the nal pathology report and the denitive surgical margins (Fig. 11.5). If partial breast reconstruction is done at the time of BCS and the patient is found postoperatively to have surgical margin involvement, reexploration can be troublesome. Therefore, the advantage of two-stage procedures relate to the possibility of accurate location of the original tumor site in the cases where positive margins are observed in the permanent pathology (27). However, the delayed-immediate approach can present some limitations. There are some technical difculties in operating on a previously treated breast, for example, recent scar tissue and brosis. The procedure can be time consuming and demands additional costs, which may have additional resource implications for community hospitals (27). INDICATIONS: CLASSIFICATION AND CHOICE OF THE RECONSTRUCTIVE METHOD Partial breast defects represent an anatomic variety that ranges from small defects that may be repaired with primary closure to large defects that involve a signicant amount of breast tissue. Each defect has its special reconstructive necessities and varying expectations for aesthetic outcome. The decision is usually determined by the surgeons preferences and the size of the defect in relation to the size of the remaining breast. On the basis of our 9 years of experience, it is possible to identify

Type III. This group includes tissue resection in large-sized breasts with ptosis. Type IIIA defects are small defects that do not cause signicant aesthetic deformity. Type IIIB defects are moderate defects that originate minor to moderate volume alterations in the breast shape or symmetry. Type IIIC defects are large defects that cause signicant volume alteration in the breast (Fig. 11.6).
Reconstructive Procedures for Classication System of Breast Conservation Surgery Defects
The majority of reconstruction techniques are performed with one of six surgical options: breast tissue advancement flaps (BAF), lateral thoracodorsal flap (LTDF), bilateral mastopexy (BM), bilateral reduction mammaplasty (BRM), latissimus dorsi myocutaneous ap (LDMF), and abdominal aps (Fig. 11.7).

Types IA, IIA, and IIIA. Defects are reconstructed with BAF in which the defect created is usually spherical or rectangular. The breast tissue is advanced along the chest wall or beneath the breast skin ap to ll the tumor defect. In these patients, no contralateral breast procedure is performed (Fig. 11.8). Type IB. In patients with lateral defects, the LTDF is performed. This local ap is planned as a wedge-shaped triangle located entirely on the lateral aspect of the thorax and then rotated to the lateral breast defect. The defect margins are sutured to the margins of the ap, and the donor site is closed

Figure 11.4. A, B: A 44-year-old patient with moderate breast asymmetry. Three years previously, the
patient underwent a left superior quadrantectomy and radiotherapy without reconstruction. C, D: Due to the presence of scar tissue and severe radiotherapy skin effects, the patient underwent a delayed reconstruction with free contralateral latissimus dorsi myocutaneous ap. In addition, due to the presence of major deformity and severe brosis, a total mastectomy was performed. E, F: Six-month postoperative appearance. G, H: Two-year postoperative appearance after the contralateral breast surgery and nipple-areola reconstruction with a very good outcome.

128

Chapter 11 Oncoplastic Surgery

129

Figure 11.5. Two-stage procedures can be delayed-immediate with initial wide local excision and then
oncoplastic reconstruction with appropriate technique at that time when the histologic margin assessment has been performed. In this approach, it is possible to postpone reconstruction until after the review of the nal pathology report and the denitive surgical margins.

130

Section I Oncology and Oncoplastic Surgery

BREAST DEFECT

Bra cup size A/B

II

Bra cup size C

III

Bra cup size D

Small defects (no distortion)

Small defects (no distortion)

Small defects (no distortion)

Moderate defects (moderate distortion)

Moderate defects (minor/moderate distortion)

Moderate defects (minor distortion)

Large defects (severe distortion)

Large defects (moderate/large distortion)

Large defects (moderate/large distortion)

Figure 11.6. Algorithm for


immediate conservative breast surgery reconstruction based on the type of breast and extent of defect.

primarily in layers (11) (see Figs. 11.5 and 11.9). In patients with central and medial tumors, the LDMF can be utilized. The ap is designed into a horizontal position, and the width of the paddle is measured according to the skin previously resected. The inferior and superior ap extensions are subjectively estimated to match the volume of glandular tissue removed (10). Local aps and especially the LTDF are useful techniques for upper outer or lower outer defects. Using tissue next to defect will provide matching color and texture to the breast. The technique provides wide access to the axilla

when the ap incision is made in continuity with that of axillary incision. Comparing the LTDF with LDMF, local aps are easy to perform, are less time consuming, require no special positioning, and involve no loss of muscle function (29). In addition, LTDF when used as alternative to LDMF will spare the muscle as a potential reserve for future use in case of local recurrence (30).

Type IC. Defects are converted to a skin-sparing mastectomy


(SSM) and reconstructed with an appropriate technique. In

RECONSTRUCTION

Bra cup size A/B

II

Bra cup size C

III

Bra cup size D

A
BAF

A
BAF

BAF

SSM mastectomy Total reconstruction

BM

BRM

Favorable

Unfavorable Favorable SSM mastectomy BRM Unfavorable SSM mastectomy

Lateral defects

Figure 11.7. Algorithm for


immediate conservative breast surgery reconstruction based on the breast type, tumor location, and reconstructive options. BAF, breast tissue advancement; BM, bilateral mastopexy; BRM, bilateral reduction mammaplasty, LTDF, lateral thoracodorsal ap; LDMF, latissimus dorsi myocutaneous ap; SSM, skin-sparing mastectomy.

LTDF

Central/Medial defects

Lateral defects

Central/Medial defects LDMF Extended LTDF Extended LDMF Total reconstruction

Figure 11.8. A, B: A 45-year-old patient with invasive ductal carcinoma (0.9 cm) of the right breast.
C, D: The patient underwent a right superior lumpectomy and sentinel lymph node biopsy, immediately followed by breast advancement glandular ap reconstruction (the breast tissue is advanced along the chest wall or beneath the breast skin ap to ll the tumor defect). In this patient, no contralateral breast procedure was performed; a total of 45 g was removed from the right breast. E, F: Two-month postoperative appearance during the radiotherapy. The right breast is more retracted than the left breast. G, H: Four-year postoperative appearance after the radiotherapy with a very good outcome.

131

132

Section I Oncology and Oncoplastic Surgery

C
primarily in layers.

Figure 11.9. The defect margins are sutured to the margins of the ap, and the donor site is closed

patients with enough abdominal tissue, an abdominal flap (pedicled/free transverse rectus abdominus myocutaneous or deep inferior epigastric perforator flap) can be an option according to the surgeons preference. In patients without an adequate abdomen, a LDMF associated with an implant can be performed.

time, consequently reducing the operative time. When performing symmetrization, the surgeon can use this opportunity to resect any suspicious breast lesion that may have been revealed by preoperative exams.

Type IIB. Defects are frequently reconstructed with BM techniques when there is sufficient breast tissue to perform the reconstruction (12,13). For tumors located in the lower region, the tumor resection can be incorporated into the sector of breast tissue removed as part of a superior pedicle mammaplasty (12). For upper region tumors, the lower breast tissue may be moved into the defect as a glandular ap and an inferior pedicle mammaplasty can be utilized (14). For inner and outer region tumors, the reduction pattern can be rotated and a superior-lateral or a superior-medial pedicle mammaplasty can be done (13) (see Fig. 11.1). The opposite-breast surgery is usually performed to match the appropriate symmetry, particularly in breasts with severe ptosis. With a well-trained surgical team, the procedure can be conducted on both sides at the same

Type IIC. Defects are analyzed individually according to the size of the breast defect in relation to the remaining breast tissue available. For this purpose, the patient is positioned upright to assess the amount of the remaining glandular tissue. Thus, type IIC defects can be subclassied into favorable and unfavorable defects. If there is enough tissue to perform an adequate breast mound shaping, the defect is classified as favorable. For the lateral defects, the extended LTDF is most commonly employed, where the inferior and superior limits are designed more obliquely with curved borders to incorporate a large amount of subcutaneous tissue from the lateral and posterior region of the thorax (11) (Figs. 11.10 to 11.12). In patients with central and medial defects, the extended LDMF can be utilized (10). Conversely, if not enough breast tissue remains, the breast defect is classied as unfavorable, and a SSM and total reconstruction is indicated (see Fig. 11.11).

Figure 11.10. A, B: A 52-year-old patient with invasive ductal carcinoma (2.9 cm) of the left breast.
C, D: The patient underwent a left superior-lateral quadrantectomy and sentinel lymph node biopsy, immediately followed by left lateral thoracodorsal ap. In this patient, no contralateral breast procedure was performed; a total of 245 g was removed from the left breast. E, F: Two-month postoperative appearance during the radiotherapy. G, H: Three-year postoperative appearance after the radiotherapy with a very good outcome.

133

Figure 11.11. A, B: A 46-year-old patient with invasive ductal carcinoma (2.5 cm) of the left breast.
C, D: The patient underwent a central-superior quadrantectomy and sentinel lymph node biopsy. Due to intraoperative positive margins and the situation of not enough breast tissue to perform the reconstruction, the breast defect was classied as unfavorable and a skin-sparing mastectomy and total reconstruction was indicated. E, F: The patient underwent reconstruction with pedicle latissimus dorsi myocutaneous ap and implant. In this patient, no contralateral breast procedure was performed. G, H: One-year postoperative appearance with a very good outcome.

134

Figure 11.12. A, B: A 38-year-old patient with invasive ductal carcinoma (2.7 cm) of the right breast.
C, D: The patient underwent a right central-superior quadrantectomy and sentinel lymph node biopsy, immediately followed by a bilateral inferior pedicle reduction mammaplasty reconstruction. On the right breast, the remaining lower breast tissue was moved into the defect as a skin-glandular ap; a total of 315 g was removed from the left breast and 385 g from the right breast. E, F: Four-month postoperative appearance during the radiotherapy. The right breast is more retracted than the left breast. G, H: Six-year postoperative appearance after the radiotherapy and the nipple-areola reconstruction with a very good outcome.

135

136

Section I Oncology and Oncoplastic Surgery

Type IIIB. Defects are frequently reconstructed with BRM techniques when the patient presents large-volume breasts and there is a sufcient amount of breast tissue (see Fig. 11.2). The most favorable tumor location is in the lower breast pole, where a conventional superior pedicle technique can be utilized (12). In patients with central tumors, an inferior pedicle is used to carry parenchyma and skin into the central defect (14) (see Fig. 11.12). Type IIIC. Breast defects are analyzed individually. When the
defect is favorable the deficiency is most frequently reconstructed with BRM. A marked reshaping of the breast with available tissue and a similar contralateral breast reduction is then performed. In patients in which the relation is not favorable, a skin-sparing mastectomy and total breast reconstruction with an appropriate technique can be indicated.

OUTCOME OF ONCOPLASTIC BREAST SURGERY


Following the recognition of BCS as an option for early breast cancer, concerns of aesthetic result and oncologic safety after oncoplastic procedures became subjects of debate. There is limited evidence in the literature on the oncologic safety and aesthetic outcome of the oncoplastic procedures (6,7,22,26,31). It has been our impression that these series are retrospective studies, generally based on a limited number of patients and sometimes only a single surgeons experience (Table 11.1). In addition, there is a small amount of data on its impact on local recurrences, distant metastasis, and overall survival (7,23). Clough et al. (22) reported 101 patients with a median followup of 46 months who were underwent BCS and oncoplastic reconstruction. Local recurrence developed in 11 cases (5-year local recurrence rate was 9.4%). Thirteen patients developed metastases, and 8 died of their disease (5-year metastasis-free survival of 82.8% and overall survival rate of 95.7%). Kronowitz et al. (6) in a review of 69 patients observed local recurrence in 2% of immediate oncoplastic reconstructions and in 16% of delayed reconstructions (p 0.06). The difference observed between the two groups can be explained by the advanced tumor stage for the patients who had a delayed reconstruction (34). Recently, Rietgens et al. (26) reported the long-term oncologic results of oncoplastic reconstruction in a series of 148 patients. With a median follow-up of 74 months, 3% developed an

ipsilateral breast cancer recurrence and 13% developed distant metastasis. According to the authors the rate of local recurrence after 5 years was low in their series when compared with 14.3% of cumulative incidence in the National Surgical Adjuvant Breast and Bowel Project trial, 9.4% after 5 years in the Institut Curie study, and 0.5% after 5 years in the Milan I trial (26). Consequently, the oncoplastic approach associated with BCS can be considered as safe as mastectomy in tumors less than 2 cm and possibly safer than the BCS. Concerning the aesthetic outcome, there is limited evidence on the oncoplastic procedures. In addition, the methods of aesthetic evaluation vary signicantly (7). Some authors reported that the amount of glandular and skin tissue resection is directly associated with the aesthetic outcome (3537). Olivotto et al. (35) and Mills et al. (36) documented that excision of a volume greater than 70 cm3 in medium-size breasts often leads to unsatisfactory aesthetic results. Clough et al. (22) used a panel of three to assess cosmetic results at 2 and 5 years. At 2 years 88% and at 5 years 82% of patients had a fair to excellent outcome. A signicantly worse cosmetic outcome was noted in the 13 patients who received preoperative radiotherapy compared to the remainder, who were given radiotherapy postoperatively (poor outcome 42.9% vs. 12.7%, p 0.02). Gendy et al. (29) retrospectively compared the aesthetic outcomes of 106 patients. Although the panel scored the cosmetic outcome quite high, the cosmetic failure rate was 18% on breast retraction assessments. The authors demonstrated an advantage for the BCS reconstruction with regard to the incidence of complications (8% vs. 14%), additional surgery (12% vs. 79%), and restricted activities (54% vs. 73%). In conclusion, BCS reconstruction appears reasonable in properly selected patients. Recognizing that there is a small risk for local recurrence and based on published experience, we believe that oncoplastic techniques could be a reasonable and safe option for earlybreast cancer patients who desire BCS. However, further studies in large series and longer follow-up may still be warranted.

MANAGING CHALLENGING PROBLEMS


CENTRALLY LOCATED BREAST CANCER Centrally located breast cancer can represent a difcult task for plastic surgeons. Despite the increasing number of studies, few reports of techniques that deal with reconstruction after central

TABLE 11.1

Oncoplastic Surgery/Reduction Mammaplasty Reconstruction


Number of Patients
20 10 11 37 69 14 28 74

Study
Clough et al. (4) Papp et al. (19) Spear et al. (15) Chang et al. (16) Petit et al. (32) Losken et al. (25) Newman et al. (33) Munhoz et al. (12) NS, not specied.

Follow-up (mo)
54 52 24 NS 21 23 24 22

Tumor Size (cm)


NS NS NS 0.65.2 NS 1.5 (0.63) 1.5 (0.15) 1.9 (0.63.9)

Positive Margins (%)


0 0 0 2.7 NS 28.6 7 9.5

Local Recurrence (%)


5 5 0 0 NS 0 0 0

Chapter 11 Oncoplastic Surgery

137

lumpectomy are available (14,18,31). In theory, several techniques for central defect reconstruction with various grades of difculty can be employed. In our experience (14), a central and superior breast defect can be better repaired with a reduction mammaplasty or mastopexy techniques. However, without adequate planning, incorporating a reduction mammoplasty with central defects secondary to BCS can be a complex procedure. For the tumors located in the upper and central region, the superior pedicle is frequently injured by the tumor resection. Thus, the remaining lower breast tissue may be moved into the defect as a dermoglandular ap, and an inferior pedicle mammaplasty technique can be utilized (14) (see Fig. 11.12). The inferior pedicle receives its blood supply directly from the fourth to sixth intercostal perforating vessels (38,39). This characteristic permits a suitable pedicle vascularization and minimizes vascular pedicle complications. In our previous study, this technique was indicated in patients with medium- or large-volume breasts with ptosis (14). All tumors were located in the upper/central breast pole and the patients presented small to moderate defects where there was enough breast tissue to perform the reconstruction. In addition, a careful evaluation of the residual breast tissue after tumor resection and the presence of the intercostal perforators should be performed. In the presence of insufcient breast tissue and an extensive undermining in the lower pole, this technique should be contraindicated. POSTOPERATIVE RADIATION AND BOOST THERAPY PLANNING All immediate techniques that involve rearrangement of glandular tissue may jeopardize the boost radiation dose delivery because the target area for the radiation is dened as the site of the tumor (3,8,1214). For this reason, coordinated planning with the multidisciplinary team, especially with the radiotherapy group, is crucial since some oncoplastic techniques alter the normal architecture of the breast (12). To locate the original tumor area we recommend orienting the tumor site by skin markings and also placing surgical clips at the tumor margins. It has been our impression, similar that observed by other authors (4042), that identication of the original tumor bed based only on physical exam, without precise imaging information, can result in missing the primary tumor bed in a substantial percentage of patients. In our experience (1214), surgical clips have not interfered with mammography and actually have helped to recognize areas at risk for recurrence. In addition, clips have not been mentioned as interfering with physical examination or cosmesis or to have added to any morbidity related to the reconstructive procedure (40). Another important issue is related to delayed reconstruction following radiotherapy. Previous studies observed that radiotherapy has a negative impact on aesthetic outcome (36,9,1215,25). Frequently, the appearance of the radiated breast is less pleasing than that of the nonradiated one, and total dose, the boost therapy, and the number of radiation elds may be involved (16,21,25,26). Losken et al. (25) emphasized that when radiation is expected, the possibility of brosis/atrophy should be taken into account in an attempt to preserve symmetry. They suggested less aggressive reductions on the ipsilateral breast to accommodate for any additional size distortion. In addition, some authors stated that oncoplastic reconstruction with radiation is best achieved using autologous, nonirradiated aps (4,6,9).

INTRAOPERATIVE FINAL MARGINS ASSESSMENT AND RECONSTRUCTION Intraoperative assessment of surgical margins requires multidisciplinary cooperation among oncologic and plastic surgeons and pathologists. Diverse techniques have been described, depending on the tumor type and size, the conservative breast surgery (CBS) technique, and whether the tumor is palpable (4345). Some methods are available, including macroscopic evaluation (46), specimen slice radiography, intraoperative ultrasonography (47), and pathologic assessment with frozen section analysis (4345). Unfortunately, all techniques can present some limitations, and, as with any other test, there is an inherent false-negative rate (43). Final margin status is determined by the use of permanent parafn-embedded sections and is considered the gold standard for margin assessment (43,45). Despite the advantages, this process is time consuming, and the results are not available until some days after the initial CBS (4345). Studies have investigated the risk factors for identifying patients with a high probability of having positive margins following CBS (27,28,45, 48,49). Younger age (27,28,48,49), histopathologic characteristics (in situ carcinoma) (27,44,48,49), and larger tumor size (28,49) have all been associated with positive margins. Our results were comparable to those of the previous studies, with young patients and larger tumor size being more likely to be associated with positive margins (28). Our data suggest that patients with those characteristics require more meticulous intraoperative margins evaluation to avoid the need for reoperation. Losken et al. (27) advocate that all patients should be informed preoperatively on the potential need for a delayed-immediate approach. In addition, these high-risk patients are better managed by staged procedures and conrmation of negative margins prior to CBS reconstruction (27,28).

POSITIVE MARGINS AND SURGICAL MANAGEMENT Techniques that involve rearrangement of glandular tissue make reexcision difcult in cases where close or positive margins are observed (28). This fact could make it difcult to locate the residual tumor and to perform margin reexcision. In our previous studies (8,1014,28), intraoperative margin evaluation was assessed by pathologic monitoring, which is based on radiologic, macroscopic, and histologic examination of frozen sections. Positive margins discovered on permanent pathology in a patient with previously negative margins were observed in 5.5% (28) (see Fig. 11.6). According to Olson et al. (45), 11.3% of patients submitted to CBS require second operations to achieve negative margins. Weinberg et al. (50) observed that 6.2% had later reexcisions, and Cendn et al. (51) reported that 19.6% of patients required additional operations to clear surgical margins. Despite these aspects, the positive margins can be effectively managed with either reexcision with/without reconstruction or with skin-sparing mastectomy and total reconstruction, depending on the extension of tissue resection, preference, and pathology. The decision to reoperate depends on the extent of tumor involvement, whether the dissection had already been extended to the chest wall or skin, and whether the patient had opted to proceed with a total reconstruction. It has been our impression that reoperation was not a disadvantage in these patients, and the negative aspect of a more extensive surgery is negligible. However, it is important that the patient should be

138

Section I Oncology and Oncoplastic Surgery

appropriately informed about the risk of further positive margins and the requirement of an additional surgery (28).

EDITORIAL COMMENTS This well-written chapter provides the South American perspective on oncoplastic surgery, which reects similar observations to those from Europe and the United States. Key points include that the goals of breast conservation should expand to include not just preserving the breast, but also taking active steps to ensure that it is not deformed as a result of the excision and radiation. Beyond that, it should challenge surgeons to consider improving the womans appearance and quality of life by actively considering whether reduction, mastopexy, or other procedures might wisely be added to the treatment plan. Munhoz also gives us a reminder that certain procedures are likely to produce unsatisfactory results from breast conservation therapy alone and therefore should involve plans for oncoplastic repair. A key principle here is that as the specimen size increases, some reconstruction becomes more and more important. We are offered a classication system that divides the possibilities based on breast size and volume discrepancies. This system, like others published elsewhere, is a useful guide to how to evaluate and plan the reconstruction. Reading this chapter is a reminder of how much more complicated oncoplastic surgery is than plastic surgery of the breast where cancer is not present. Surgeons performing oncoplastic surgery need to be versatile and creative in order to deal with the many different presentations in these patients. At the same time, a high level of judgment is required regarding timing, coordinating with other oncologists, and knowing when to alter the plan in favor of mastectomy and reconstruction. This chapter illustrates several different techniques for correcting a variety of challenging defects. All these methods are valuable tools that have specic application for certain defects. I particularly like the lateral thoracodorsal ap. In an ideal world, there will come a time when all women with breast cancer are offered and encouraged to avail themselves of plastic surgery and oncoplastic surgery consultation. This effort to improve the cosmetic results of breast cancer treatment should parallel the efforts at curing the disease and prolonging survival. S.L.S. The concept of oncoplastic surgery has generated much enthusiasm among surgeons who operate on the breast, both oncologic surgeons and plastic surgeons. Indeed, all breast surgery should be oncoplastic surgery, if we use Dr. Munhoz denition that oncoplastic surgery combines principles of oncologic and plastic surgery techniques to obtain oncologically sound and aesthetically pleasing results. Dr. Munhoz has given us a classication of breast type and suitability for different types of oncoplastic procedures that is very helpful, not only for the planning of surgery for an individual patient, but also for giving professionals a lexicon for communicating with each other and disseminating information.

Oncoplastic operations are designer operations. No two are the same. Breast size, degree of ptosis, location of tumor, prior surgery on the breast, prior radiation, and depth of tumor all impact the planning for the operation and the outcome. The oncologic surgeon and the plastic surgeon must work together as a team, with the knowledge of the location of the tumor, the expected extent of the tumor, and the potential for adjuvant therapy, to plan an operation that gives excellent results preferably as a onestage procedure. The goal is to not burn any bridges should nal histology, staging, or patient preference change the plan after the rst operation. It is challenging to communicate the vision of the best outcome to the patient and the steps needed to get there. She is usually most interested in having the cancer removed from her breast and less interested in having multiple operations. There are inherent difculties in oncoplastic surgery. Finding a positive margin on permanent histology can be a disappointment to the clinicians and the patient. Properly marking the location of the margins with clips, especially if there is signicant tissue rearrangement, is mandatory. Marking all tissue removed for orientation is also essential. It will be interesting to see the interplay of oncoplastic surgery and partial breast irradiation in the future. S.C.W.

REFERENCES
1. Veronesi U, Cascinelli N, Mariani L, et al. Twenty-year follow-up of a randomized study comparing breast-conserving surgery with radical mastectomy for early breast cancer. N Engl J Med 2002;347:12271235. 2. Munhoz AM, Aldrighi C, Ferreira MC. Paradigms in oncoplastic breast surgery: A careful assessment of the oncological need and aesthetic objective. Breast J 2007;13:326327. 3. Slavin SA, Halperin T. Reconstruction of the breast conservation deformity. Semin Plast Surg. 2004;18:89100. 4. Clough K, Kroll S, Audretsch W. An approach to the repair of partial mastectomy defects. Plast Reconstr Surg 1999;104(2):409420. 5. Clough KB, Thomas SS, Fitoussi AD, et al. Reconstruction after conservative treatment for breast cancer: cosmetic sequelae classication revisited. Plast Reconstr Surg 2004;114: 17431750. 6. Kronowitz SJ, Feledy JA, Hunt KK, et al. Determining the optimal approach to breast reconstruction after partial mastectomy. Plast Reconstr Surg 2006;117:111. 7. Asgeirsson KS, Rasheed T, McCulley SJ, et al. Oncological and cosmetic outcomes of oncoplastic breast conserving surgery. Eur J Surg Oncol 2005;31:817827. 8. Munhoz AM, Montag E, Arruda E, et al. Assessment of immediate conservative breast surgery reconstruction: a classication system of defects revisited and an algorithm for selecting the appropriate technique. Plast Reconstr Surg 2008;121:716727. 9. Hamdi M, Woli J, Van Landuyt K. Partial mastectomy reconstruction. Clin Plast Surg 2007;34:5162. 10. Munhoz AM, Montag E, Arruda E, et al. Outcome analysis of breast-conservation surgery and immediate latissimus dorsi ap reconstruction in patients with T1 to T2 breast cancer. Plast Reconstr Surg 2005;116:741750. 11. Munhoz AM, Montag E, Arruda E, et al. The role of the lateral thoracodorsal fasciocutaneous ap in immediate conservative breast surgery reconstruction. Plast Reconstr Surg 2006;117:16991709. 12. Munhoz AM, Montag E, Arruda E, et al. Critical analysis of reduction mammaplasty techniques in combination with conservative breast surgery for early breast cancer treatment. Plast Reconstr Surg 2006;117:10911103. 13. Munhoz AM, Montag E, Arruda E, et al. Superior-medial dermoglandular pedicle reduction mammaplasty for immediate conservative breast surgery reconstruction. Ann Plast Surg 2006;57:502511. 14. Munhoz AM, Montag E, Arruda E, et al. Reliability of inferior dermoglandular pedicle reduction mammaplasty in reconstruction of partial mastectomy defects: surgical planning and outcome. Breast 2007;16:577589. 15. Spear SL, Pelletiere CV, Wolfe AJ, et al. Experience with reduction mammaplasty combined with breast conservation therapy in breast cancer. Plast Reconstr Surg 2003;111: 11021110. 16. Chang E, Johnson N, Webber B, et al. Bilateral reduction mammoplasty in combination with lumpectomy for treatment of breast cancer in patients. Am J Surg 2004;187:647655. 17. Audretsch W, Rezai M, Kolotas C, et al. Tumor-specic immediate reconstruction in breast cancer patients. Perspect Plast Surg 1998;11:7179.

Chapter 11 Oncoplastic Surgery


18. Huemer GM, Schrenk P, Moser F, et al. Oncoplastic techniques allow breast-conserving treatment in centrally located breast cancers. Plast Reconstr Surg 2007;120:390398. 19. Papp C, Wechselberger G, Schoeller T. Autologous breast reconstruction after breast-conserving cancer surgery. Plast Reconstr Surg 1998;102:19321939. 20. Brierley JD, Paterson IC, Lallemand RC, et al. The inuence of breast size on late radiation reaction following excision and radiotherapy for early breast cancer. Clin Oncol 1991; 3:612. 21. Gray JR, McCormick B, Cox L, et al. Primary breast irradiation in large-breasted or heavy women: analysis of cosmetic outcome. Int J Radiat Oncol Biol Phys 1991;21:347356. 22. Clough KB, Lewis JS, Couturaud B, et al. Oncoplastic techniques allow extensive resection for breast-conserving therapy of breast carcinomas. Ann Surg 2003;237:2634. 23. Kaur N, Petit JY, Rietjens M, et al. Comparative study of surgical margins in oncoplastic surgery and quadrantectomy in breast cancer. Ann Surg Oncol 2005;12:539549. 24. Ricci MD, Munhoz AM, Geribela A, et al. The inuence of reduction mammaplasty techniques in synchronous breast cancer diagnosis and metachronous breast cancer prevention. Ann Plast Surg 2006;57:125136. 25. Losken A, Elwood ET, Styblo TM, et al. The role of reduction mammaplasty in reconstructing partial mastectomy defects. Plast Reconstr Surg 2002;109:968976. 26. Rietjens M, Urban CA, Rey PC, et al. Long-term oncological results of breast conservative treatment with oncoplastic surgery. Breast 2007;16:387395. 27. Losken A, Styblo TM, Carlson GW, et al. Management algorithm and outcome evaluation of partial mastectomy defects using reduction or mastopexy techniques. Ann Plast Surg 2007;59:235242. 28. Munhoz AM, Montag E, Arruda E, et al. Immediate reconstruction following breast-conserving surgery: management of the positive surgical margins and inuence on secondary reconstruction. Breast 2009;18:4754. 29. Gendy RK, Able JA, Rainsbury RM. Impact of skin-sparing mastectomy with immediate reconstruction and breast-sparing reconstruction with miniaps on the outcomes of oncoplastic breast surgery. Br J Surg 2003;90:433439. 30. Almasad JK, Salah B. Breast reconstruction by local aps after conserving surgery for breast cancer: an added asset to oncoplastic techniques. Breast J 2008;14:340344. 31. Fitzal F, Mittlboeck M, Trischler H. Breast-conserving therapy for centrally located breast cancer. Ann Surg 2008;247:470476. 32. Petit JY, Rietjens M, Garusi C. Breast reconstructive techniques in cancer patients: which one, when to apply, which immediate and long term risks? Crit Rev Oncol Hematol 2001;38:231239. 33. Newman LA, Kuerer HM, McNeese MD, et al. Reduction mammoplasty improves breast conservation therapy in patients with macromastia. Am J Surg 2001;181:215221.

139

34. Nahabedian M. Determining the optimal approach to breast reconstruction after partial mastectomy (discussion). Plast Reconstr Surg 2006;117:1214. 35. Olivotto IA, Rose MA, Osteen RT, et al. Late cosmetic outcome after conservative surgery and radiotherapy: analysis of causes of cosmetic failure. Int J Radiat Oncol Biol Phys 1989;17:74753. 36. Mills JM, Schultz DJ, Solin LJ. Preservation of cosmesis with low complication risk after conservative surgery and radiotherapy for ductal carcinoma in situ of the breast. Int J Radiat Oncol Biol Phys 1997;39:637641. 37. Cochrane R, Valasiadou P, Wilson A, et al. Cosmesis and satisfaction after breast-conserving surgery correlates with the percentage of breast volume excised. Br J Surg 2003;90:15051509. 38. Ribeiro L. A new technique for reduction mammaplasty. Plast Reconstr Surg 1975;55:330341. 39. Courtiss EH, Goldwyn RM. Reduction mammaplasty by the inferior pedicle technique. Plast Reconstr Surg 1977;59:500511. 40. Solin L, Danoff B, Schwartz G, et al. A practical technique for the localization of the tumor volume in denitive irradiation of the breast. Int J Radiat Oncol Biol Phys 1985;11:12151220. 41. Solin L, Chu J, Larsen R, et al. Determination of depth for electron breast boosts. Int J Radiat Oncol Biol Phys 1987;13:19151919. 42. Regine W, Ayyangar K, Komarnickv L, et al. Computer-CT planning of the electron boost in denitive breast irradiation. Int J Radiat Oncol Biol Phys 1991;20:121125. 43. Laucirica R. Intraoperative assessment of the breast: guidelines and potential pitfalls. Arch Pathol Lab Med 2005;129:15651583. 44. Cabioglu N, Hunt KK, Sahin AA, et al. Role for intraoperative margin assessment in patients undergoing breast-conserving surgery. Ann Surg Oncol 2007;14:14581467. 45. Olson TP, Harter J, Muoz A, et al. Frozen section analysis for intraoperative margin assessment during breast-conserving surgery results in low rates of re-excision and local recurrence. Ann Surg Oncol 2007;14(10):29532960. 46. Balch GC, Mithani SK, Simpson JF, et al. Accuracy of intraoperative examination of surgical margin status in women undergoing partial mastectomy for breast malignancy. Am Surg 2005;71:2231. 47. Singletary SE. Surgical margins in patients with early-stage breast cancer treated with breast conservation therapy. Am J Surg 2002;184:383390. 48. Obedian E, Haffty BG. Negative margin status improves local control in conservatively managed breast cancer patients. Cancer J Sci Am 2000;6:2837. 49. Tartter PI, Kaplan J, Bleiweiss I, et al. Lumpectomy margins, re-excision, and local recurrence of breast cancer. Am J Surg 2000;179:8190. 50. Weinberg E, Cox C, Dupont E, et al. Local recurrence in lumpectomy patients after imprint cytology margin evaluation. Am J Surg 2004;188:349357. 51. Cendn JC, Coco D, Copeland EM. Accuracy of intraoperative frozen-section analysis of breast cancer lumpectomy margins. J Am Coll Surg 2005;201:194203.

CHAPTER

12
Reconstruction of Partial Mastectomy Defects: Classications and Methods
INTRODUCTION
Reconstructive breast surgery is unique in its demand for ongoing refinement and continued restructuring to further improve outcome and patient satisfaction. Partial breast reconstruction is one of those areas where exciting new trends have been developed that have the potential to signicantly change our practice strategies and the way we manage women with breast cancer. Although originally used to improve the cosmetic results by reconstructing breast conservation defects following radiation therapy, the shift now focuses more on recognizing the potentially unfavorable partial mastectomy defect and reconstructing this defect in an attempt to prevent the deformity. This combination allows removal of larger amounts of breast tissue with safer margins without compromising the cosmetic outcome. Women with breast cancer no longer need to accept significant deformities in order to preserve their breasts. This oncoplastic concept applies the principles of surgical oncology with those of plastic surgery, which in this chapter will be focused on those women undergoing breast conservation therapy (BCT). Werner Audretsch is credited for his pioneering work in the eld of oncoplastic breast surgery, an approach that was initially more popular in Europe and the United Kingdom but has recently gained acceptance and popularity worldwide (1). The oncoplastic terminology will be used in this chapter as it applies to the immediate reconstruction of the partial mastectomy defect. This field has clearly been driven by both patient demands and the development of combined surgical techniques made possible through greater interaction between specialties.

Albert Losken

Resection of 15% to 20% breast parenchyma in small breasts and 30% in large breasts Tumors located in aesthetically sensitive areas: central, medial, inferior Defect involving skin retracting down to the underlying chest wall Nipple-areolar malposition Breast size and degree of ptosis Higher body mass index (BMI) Need for reexcision for margin control Radiation therapy Traditionally, women with large breasts have been deemed poor candidates for breast conservation surgery because of reduced effectiveness, increased complications, and worse cosmetic outcome. The postradiation sequela in women with macromastia is signicantly worse, leading to poor long-term symmetry. Radiation-induced brosis is thought to be greater in women with larger breasts, given the dosing inhomogeneity (5,6). Late-radiation brosis occurs 36% of the time in patients with larger breasts, compared to 3.6% for patients with smaller breasts. Higher doses of radiation therapy are often necessary in women with larger breasts, contributing to morbidity and adversely affecting the appearance. The cosmetic results following breast-conserving therapy in women with large breasts are also reduced. Clark et al. showed excellent results in 100% of women with A cup breasts following BCT, compared to 50% in women with D cup breasts (7). Women with central or lower quadrant tumors have also been shown to have a worse cosmetic outcome because of tumor location, especially when a signicant amount of skin is removed as well. Lower quadrant tumors give twice as poor cosmetic results as lumpectomies in other quadrants. Central breast tumors close to the areolar have in the past been a contraindication to BCT. The tumor-tobreast ratio is one of the most important factors when predicting the potential for a poor outcome. In general, when more than 20% of the breast is excised with partial mastectomy, the cosmetic result is likely to be unfavorable. Younger patient age and elevated BMI have also been shown to be predictors of asymmetry after BCT (8).

UNDERSTANDING THE DEFECT


The primary goals of BCT are to adequately treat the breast cancer and minimize local recurrence while preserving breast shape and symmetry. However, there remains an innate conict between the goals of oncology and cosmesis, with the former being to eliminate all locoregional disease and the latter relying on preservation of as much breast tissue as possible for optimal aesthetic outcome. The wider the margin of resection, the lower is the risk of local recurrence (2,3), and it often becomes a dilemma for the surgeon to meet both these endpoints (Fig. 12.1). Up to 30% of women will have a residual deformity that may require surgical correction (4). There are numerous factors that contribute to poor cosmetic results following BCT. They essentially are related to (a) the amount of tissue resected in relation to the breast tissue preserved and (b) the deleterious long-term effects of radiation therapy. Factors contributing to poor cosmesis after BCT include the following:

CLASSIFYING THE PARTIAL MASTECTOMY DEFECT


Numerous classications systems have been developed for the late BCT deformity in terms of types 1 to 3 with increasing amount of distortion (4,9,10) and have been used to determined reconstructive options. The data are limited when it comes to describing partial mastectomy defects. We recently expanded on some of the BCT classications in an attempt to objectively describe the defect at the time of resection and the

140

Chapter 12 Reconstruction of Partial Mastectomy Defects

141

the breast incisions and parenchymal resection. Neoadjuvant chemotherapy will also downsize the tumor and reduce the required amount of parenchyma resection. Limiting the volume of resection will minimize the incidence of poor cosmetic results. Attention to simple defect closure, including breast advancement aps and full-thickness closures, is now commonly given by most breast surgeons, and these are ways to improve results. The more complex defects with potential for poor cosmesis will often benet from partial breast reconstruction.

INDICATIONS FOR PARTIAL BREAST RECONSTRUCTION


Figure 12.1. Dilemma: clash of interests. (Modied from
Donegan WL, Spratt JS. Cancer of the Breast. 4th ed. Philadelphia, PA: Saunders; 1995.)

various reconstructive techniques that might prevent the deformity (11) (Table 12.1). An important part of any classication system will be the extent of the defect, how much skin is removed, how much tissue is left behind, and where it is in relation to the nipple-areolar complex.

PREVENTING THE PARTIAL MASTECTOMY DEFECT


Although the adverse effects of radiation therapy are often unavoidable, there are principles that can be applied to the resection with or without reconstructive techniques that can be used to minimize the incidence of poor cosmetic results. The oncoplastic approach applies the principles of plastic surgery to the resection as well. A deformity can often be avoided by correctly orienting

The two main reasons to reconstruct partial mastectomy defects are to (a) increase the indications for BCT, making breast conservation practical in patients who otherwise might require a mastectomy, and (b) to minimize the potential for a poor aesthetic result (Table 12.2). The decision is typically based on tumor characteristics and breast shape and size. Based on these factors contributing to a poor aesthetic outcome, the oncoplastic approach is indicated whenever the potential for a poor cosmetic result exists or patients have tumors in whom a standard lumpectomy would lead to breast deformity or gross asymmetry. In particular, this includes women with large tumors, large breasts, lower quadrant tumors, central mound tumors, or a high expected tumor-to-breast ratio. Factors in addition to cosmetic reasons as an indication for this approach include oncologic issues. Important indications include situations where the surgeon is concerned about the potential for negative margins with standard resection and, based on initial pathology or breast imaging studies, needs to perform a wider excision in order for the patient to be a candidate for breast-conserving surgery. The oncoplastic approach broadens the indications for BCT, as these patients might otherwise

TABLE 12.1

Classication of the Partial Mastectomy Defect With Potential Outcome and Treatment Options
Potential Outcome
Breast shape is preserved with acceptable symmetry Size and shape deciency with noticeable distortion and asymmetry Volume replacement procedures Volume replacement technique

Description
Type 1 (favorable) Small, peripheral defect Large or small breasts Medium to large defect Central defects Small breasts, with or without ptosis Medium to large breasts, with or without ptosis

Treatment
Primary closure, breast tissue advancement ap

Type 2 (unfavorable) Type 2a Type 2b

Type 3 (unfavorable)

Extensive resection with little remaining breast tissue Large or small breasts

Quadrantectomy defect outside standard Wise pattern Any lumpectomy defect Quadrantectomy defect within standard Wise pattern Major deciency

Volume displacement techniques Mastectomy and reconstruction

From Losken A, Hamdi M. Partial breast reconstruction: current perspectives. Plast Reconstr Surg 2009;124(3):722736.

142

Section I Oncology and Oncoplastic Surgery

TABLE 12.2
Cosmetic Reasons
High tumor-to-breast ratio (20%) Tumor location: central, inferior, medial Macromastia Large tumor Patient desires smaller breasts Signicant ptosis, or breast asymmetry

Indications for Immediate Partial Mastectomy Reconstruction


Oncologic Reasons
Concern about clear margins Wide excision required Poor candidate for mastectomy and reconstruction (i.e., age, breast size) Patient desires breast conservation therapy

sue remains following partial resection, tissue is recruited from outside the breast mound using ap techniques. When aps are required to reconstruct the partial mastectomy defect, this has been referred to as volume replacement of flap reconstruction. These also range in complexity from local rotational aps from the axilla, lateral chest wall, and abdomen, to local myocutaneous aps, to free aps and perforator aps (1721).

TREATMENT ALGORITHM
Different algorithms have been described in an attempt to simplify the reconstructive process. There is unfortunately a lack of standardization when it comes to partial breast reconstruction, which makes comparative studies difcult. The decision as to which procedure is more appropriate is multifactorial; however, it is ultimately determined by breast size, tumor size, and tumor location (Fig. 12.3). Other factors are also important, including patient risks and desires, tumor biology, and surgeon comfort level with the various techniques. Another way of looking at this is to evaluate the amount of breast tissue that remains following completion of the partial mastectomy and where that tissue is in relation to the nipple-areolar complex since this will dictate the most appropriate reconstruction option for that particular case. Not unlike the reconstruction of Mohs defects, these oncoplastic reconstructions can be both challenging and rewarding. Adhering to strict algorithms is difcult since every case is different. Being familiar with the various reconstructive tools will allow reconstruction of almost any partial mastectomy defect. It is important to keep in mind that when the defect is extensive with little remaining breast tissue, completion mastectomy and immediate reconstruction is often the more appropriate option. Some simple rules of thumb exist for reconstructing partial mastectomy defects. Large or moderate-sized breasts or ptotic breasts with sufcient parenchyma remaining following resection are amenable to volume displacement or reshaping procedures (Fig. 12.4). Quadrantectomy-type resections are possible when they are within the standard Wise pattern markings. In smaller or nonptotic breasts, when additional volume is required to match the opposite breast or when skin is required to replace a resection that included parenchyma and skin, volume

have required a mastectomy, the reconstruction of which (i.e., macromastia) often being more challenging with less favorable cosmetic results. Additional indications include women who desire breast conservation despite potential adverse conditions, as well as older women with large, ptotic breasts in whom mastectomy and reconstruction would be difcult.

CLASSIFICATION OF THE RECONSTRUCTIVE TECHNIQUES


Partial breast reconstruction uses many of the same familiar principles and techniques used for total breast reconstruction following mastectomy. However, additional techniques have been described that are useful following breast preservation, using the remaining breast tissue and local tissue to repair partial defects. In general, reconstructive techniques involve either using breast tissue to reshape the breast or using aps as volume replacement (Fig. 12.2). The form of partial reconstruction using residual breast tissue has been referred to as volume displacement, parenchymal remodeling, or simply breast reshaping. These techniques range in complexity from simple advancement aps (12) to simple glandular aps to mastopexy and reduction techniques (1316). When insufcient breast tis-

Figure 12.2. Reconstructive techniques


based on breast and tumor size.

Chapter 12 Reconstruction of Partial Mastectomy Defects

143

Figure 12.3. Treatment algorithm


for the partial mastectomy defect.

replacement procedures, including volume and skin, are required (Fig. 12.5). Quadrantectomy-type resections in small breasts and in the upper or outer quadrant invariably require a ap reconstruction to preserve shape. See Table 12.3. VOLUME DISPLACEMENT TECHNIQUES The breast-reshaping procedures all essentially rely on advancement, rotation, or transposition of a large area of breast to ll a small or moderate-sized defect. This absorbs the volume loss over a larger area. In its simplest form, it entails mobilizing the breastplate from the area immediately around the defect in a breast ap advancement technique (12). The dissection is over the pectoralis muscle and essentially involves a full-thickness segment of breast fibroglandular tissue advanced to fill the dead space. These procedures are indicated in the type 1 deformities for small to medium-sized breasts where the resection does not lead to any signicant volume alteration that might cause breast asymmetry. A contralateral symmetry procedure is typically not required.

TABLE 12.3
Volume Displacement Techniques

Partial Mastectomy Reconstruction Techniques


Volume Replacement Techniques
Adjacent or distant tissue transfer, volume preserving Implant augmentation: rare Local aps Fasciocutaneous Perforator aps Latissimus dorsi musculocutaneous ap Distant aps Other Stem cells, fat injections Omentum

Parenchymal remodeling, volume shrinkage Primary closure Mirror biopsy/excision Batwing mastopexy Breast ap advancement technique Nipple-areolar centralization Reduction mastopexy techniques

Figure 12.4. A: A 33-year old woman with stage III breast cancer who had an excellent response to preoperative chemotherapy desired breast conservation. B: She had a wire-guided lumpectomy (100 g) from the upper medial quadrant, leaving a moderate-sized defect. In order to minimize the potential for a poor cosmetic result, she underwent a simultaneous bilateral breast reduction (total volumes 250 g left and 150 g right). C: The nipple was moved on an inferiorly based dermatoglandular pedicle with the central attachments intact and used in part to ll the upper pole volume void. D: Her result is shown at 1 year following completion of right breast radiation therapy. (From Losken A and Bostwick J III. Breast reconstruction. In: Wood WC, Staley CA, and Skandalakis JE, eds. The Anatomic Basis of Tumor Surgery. Springer, New York; 2010:166194.)

A,B

Figure 12.5. Presurgery and postsurgery in latissimus dorsi myocutaneous ap reconstruction. Threedimensional replacement of the upper pole after partial mastectomy, including radiated skin of the tumor bed, was performed to achieve sufcient clearance in the third dimension. There was satisfactory rearrangement of the bilateral breast shape and size reduction with the positive side effect of orthopedic relief and appearance improvement. Shown are early and late results of postradiation reconstruction by means of the latissimus dorsi ap.

144

Chapter 12 Reconstruction of Partial Mastectomy Defects

145

Perhaps the most popular and versatile breast-reshaping options are the mastopexy or reduction techniques. The ideal patient is one in whom the tumor can be excised within the expected breast reduction specimen in medium to large or ptotic breasts where sufcient breast parenchyma remains following resection to reshape the mound (type 2b defects) (Fig. 12.6). Masetti et al. described a four-step design for oncoplastic operations: (a) planning skin incisions and parenchymal excisions following reduction/mastopexy templates, (b) providing parenchymal reshaping following excision, (c) repositioning the nipple, and (d) correcting the contralateral breast for symmetry (14). Any moderate to large breast can be reconstructed using these techniques unless a skin deformity exists beyond the standard Wise pattern (type 2a defect).

Plastic surgeons are familiar with these techniques, making the incorporation of this approach into their reconstructive practice an easy addition. There has been an exponential increase in reports over the last few years describing these techniques showing generous resections, acceptable morbidity, and good outcomes. In women with large or ptotic breasts, the numerous reduction patterns or pedicle designs will invariably allow remodeling of a defect in any location and any size, as long as sufcient breast tissue and skin is available. Creative mammaplasty designs can be made for complete removal of the lesion and reshaping of the mound for both lumpectomy- and quadrantectomy-type defects (Figs. 12.7 and 12.8). Preoperative markings are important, and a decision is made on pedicle design depending on tumor location. Typically, if the pedicle

A B

C D

Figure 12.6. A, B: A 49-year-old woman with macromastia


and right-sided breast cancer. C: She is marked preoperatively with standard Wise pattern markings. D: Her defect is shown following lumpectomy with positive margins superiorly. E: She was taken to the operating room in a delayed-immediate fashion, and additional tissue was resected, ensuring negative margins. (continued )

146

Section I Oncology and Oncoplastic Surgery

Figure 12.6. (Continued ) F: An inferior pedicle was deepithelialized. G, H: However, given the potential
for volume void above the nipple-areolar reconstruction, the breast parenchyma was plicated above the nipple to create volume and ll the defect. J, K: Her result is shown 1 year following completion of radiation therapy.

points to or can be rotated into the defect, it can be used. The Wise pattern markings are more versatile, allowing tumor resection in any breast quadrant. Once the resection is performed, the cavity is inspected, paying attention to the defect location in relation to the nipple, as well as the remaining breast tissue. The reconstructive goals include (a) preservation of nipple viability,

(b) reshaping of breast mound, and (c) closure of dead space. The nipple and dermatoglandular pedicle is dissected, and remaining tissue is resected if necessary for completion of the reduction. Occasionally, additional dermatoglandular or glandular pedicles can be created from tissue that might otherwise have been resected, and they can be rotated to autoaugment the defect

Chapter 12 Reconstruction of Partial Mastectomy Defects

147

Figure 12.7. A, B: A 50-year-old woman with a right medial breast cancer. C, D: She underwent a 100-g
partial mastectomy from above the nipple. Margin conrmation was cleared, and she was taken back to the operating room for reconstruction 2 weeks later. E, F: An extended superolateral pedicle was used to rotate into the defect and ll the volume void in this cosmetically sensitive area. No additional tissue was removed. A contralateral mastopexy was performed for symmetry. (continued )

148

Section I Oncology and Oncoplastic Surgery

Figure 12.7. (Continued ) G, H: Her shape and symmetry are reasonable at 9 months following completion
of radiation therapy to the right breast.

Figure 12.8. Medial defect with quadrantectomy resection. A, B: Presurgery. Small, symmetric breasts with bilateral mirror lesions. C, D: Postsurgery. (continued )

Chapter 12 Reconstruction of Partial Mastectomy Defects

149

Figure 12.8. (Continued ) E: Bilateral surgery without a visible reduction scar after radiation on the right
and a visible scar on the nonradiated left side.

(Fig. 12.9). The contralateral procedure is performed using a similar technique. The ipsilateral side is typically kept about 10% larger to allow for radiation brosis. Additional tissue sampling from the ipsilateral or contralateral breast is also possible using this technique (Fig. 12.10).

Lower quadrant tumors in women with larger breasts are ideally suited for the oncoplastic approach (15). Quadrantectomytype resections are possible, removing skin and parenchyma from this location and reshaping the breast using a superior or superomedial pedicle. Lower pole tumors in moderate-sized

Figure 12.9. A: A 53-year-old woman had a history of right upper outer ductal carcinoma in situ.
B, C: She underwent a 235-g partial mastectomy and axillary node dissection through the Wise pattern markings. D: A superomedial pedicle was chosen for nipple viability. Her defect was reconstructed with an inferiorly based deepithelialized ap that was rotated superiorly to ll the dead space. (continued )

150

Section I Oncology and Oncoplastic Surgery

Figure 12.9. (Continued ) E: A total of 395 g was removed from the right breast and 390 g from the left
breast. F: Her result is shown after completion of radiation therapy.

breasts can be excised along with skin as needed in the usual vertical pattern utilizing a superior pedicle followed by plication of the vertical pillars and vertical reduction on the contralateral side. Upper quadrant tumors can be lled as long as the defect is under the skin (lumpectomy type). Autoaugmentation techniques have become popular to ll the dead space and maintain shape. Inferior or medial pedicles allow for safe excisions in the

upper half of the breast without impairing nipple viability, and parenchyma is often rearranged when insufcient tissue remains in the upper pole to maintain the desired fullness (13) (Fig. 12.11). When skin is resected in the upper half of the breast, such remodeling techniques are not possible. Lateral or upper outer quadrant defects allow parenchymal remodeling using the superomedial pedicle. These types of reconstructions become

Figure 12.10. A: A 53-year-old woman had a history of right-sided breast cancer and some suspicious
areas on the left breast. BD: Her preoperative markings were made following completion of wire placement and mammographic localization was demonstrated. (continued )

Figure 12.10. (Continued ) E: She underwent a right lateral


partial mastectomy (200 g) and an additional 80 g with her reduction specimen. F: Cavity samples were sent prior to the reconstruction. Her left biopsy was negative for carcinoma, with the specimen weight 90 g, and an additional 250 g was removed from that side. G: She is shown just prior to radiation therapy on the right breast. (From: Kuerer HM. Kuerers Breast Surgical Oncology. McGraw-Hill, 2010, with permission.)

Figure 12.11. AC: A 59-year-old woman with inltrating ductal carcinoma in the upper quadrant.
D: Preoperative markings demonstrate the standard Wise pattern. (continued )

151

152

Section I Oncology and Oncoplastic Surgery

Figure 12.11. (Continued ) E: Her defect demonstrates volume loss above the nipple-areola complex, following a 124-g partial mastectomy. F: An extended superomedial pedicle was deepithelialized and used to preserve nipple viability and (G) rotated superiorly to ll the defect above the nipple in the upper pole. H: An additional 200 g was removed from the lower pole, and her result demonstrates good contour. A contralateral reduction was performed, removing 387 g. IK: She is shown 6 months postoperative with preservation of upper pole shape.

Chapter 12 Reconstruction of Partial Mastectomy Defects

153

difcult when skin is resected with the specimen and are better suited for the lumpectomy-type defects. In women with mediumsized ptotic breasts, the superomedial pedicle can be extended down to the inframammary fold as an autoaugmentated pedicle. This can then be rotated to ll a lateral volume void. The vertical pillars are then plicated in the usual fashion to maintain shape. If tissue is removed from above the Wise pattern markings, a ap is often required. In women with macromastia, a reduction can still be performed utilizing the inferior pedicle skin to replace missing breast skin even when above the Wise markings (Fig. 12.12). Central tumors have in the past been considered relative contraindications to BCT; however, with the oncoplastic

approach in women with macromastia the tumor and nipple-areolar complex can be widely excised and reconstructed using a variety of techniques (2224). The mound can be remodeled in the inverted-T closure pattern, similar to breast amputation reduction techniques (Fig. 12.13). The nipple is then reconstructed later using the reconstruction technique of choice. Another option if the tumor is located more superiorly or laterally is to perform a central elliptical excision of skin, nipple, and parenchyma and mirror image contralateral reduction for symmetry. A third option includes creation of a skin island on a dermatoglandular pedicle to rotate into the central defect to allow for shape preservation and nipple reconstruction. The breast is marked preoperatively for an inverted T or a vertical

Figure 12.12. A, B: A 40-year-old woman with inltrating


ductal cancer and ductal carcinoma in situ on the lateral aspect of her right breast. She has macromastia and was scheduled for an oncoplastic reduction with partial mastectomy. C: Location of the tumor and margin status necessitated resection of parenchyma and skin from above the proposed Wise markings. The weight of the specimen was 500 g. D, E: An inferior pedicle was created leaving skin laterally on the pedicle to replace the resected breast skin. A total of 1,290 g of breast tissue was removed from the right, and a contralateral reduction was performed, removing 1,650 g. (continued )

154

Section I Oncology and Oncoplastic Surgery

Figure 12.12. (Continued ) F, G: She is shown at completion of radiation therapy to the right breast with
reasonable shape and symmetry.

Figure 12.13. A: A 49-year-old woman had a right-sided subareolar invasive ductal carcinoma. B: She
underwent a 100-g resection that included the nipple-areolar complex followed by breast amputation of 815 g on the right and 1,215 g on the contralateral side. C: Results at 2 years following radiation therapy. D: Results after completion of nipple-areolar reconstruction on the right.

Chapter 12 Reconstruction of Partial Mastectomy Defects

155

Figure 12.14. A, B: Presurgery. Ptosis and anisomasty in favor of the left breast. Tumor location in the lateral pole of the left breast. C: Postsurgery. Bilateral surgery in a quadrantectomy, axillary dissection, and radiation therapy case, horizontal reduction mammoplasty. D: Long-term result after radiation therapy, no visible scar.
approach, depending on breast size, and the skin island is brought in from inferior or medial. Additional mastopexy options exist for oncoplastic breast conservation (12). The donut mastopexy allows a breast segment to be removed through a periareolar incision and is useful for segmentally distributed cancers in the upper or lateral potion of the breast. The batwing mastopexy involves a full-thickness excision of lesions deep within the breast centrally or adjacent to the nipple-areolar complex (Fig. 12.14). The two similar half-circle incisions with angled wings on either side of the areolar allow advancement of the broglandular tissue to close the defect. Since this removes sufcient breast tissue and skin to alter the size of the breast and nipple position, a similar contralateral lift is occasionally required to achieve symmetry. In addition, if the patient is a candidate for BCT and has multiple areas that need to be resected, as long as sufcient tissue remains, remodeling techniques can be used in a similar fashion (Fig. 12.15). VOLUME REPLACEMENT TECHNIQUES Partial mastectomy defects in women with small to mediumsized breasts are often difcult to reconstruct (9,10). Women with large tumor-to-breast ratios and women with small to moderate breasts who have insufcient residual breast tissue for rearrangement require partial reconstruction using nonbreast local or distant aps. This is now well accepted in the evolution of breast cancer surgery and provides breast symmetry without remodeling the contralateral breast (25). Local aps are often indicated in small or moderate-volume breasts with insufcient tissue remains following resection for volume displacement techniques (Fig. 12.16). The usual techniques included (a) rhomboid ap, (b) subaxillary ap, (c) superiorbased lateral thoracodorsal ap, (d) inferior-based lateral thoracodorsal ap, and (e) extended lateral thoracodorsal ap. Small lateral defects (less than 10% of breast size) can be closed with local aps. Clough et al. (9) described using the subaxillary area as a transposition ap, and Munhoz et al. more recently demonstrated how the lateral thoracodorsal ap is ideal for lateral defects, especially in obese patients (20). These aps essentially rotate or transfer skin and subaxillary fat or skin and breast parenchyma into the defect. The same principles can be applied to local aps taken from outside the breast as described previously or even from within the breast (volume displacement techniques). Attention to ap design is important to ensure ap

156

Section I Oncology and Oncoplastic Surgery

Figure 12.15. A, B: A 63-year-old woman with right inltrating cancer laterally and a suspicious lesion medially. C: Preoperative markings were made after placement of the stereotactic wires. D: She underwent two wire-guided biopsies, leaving a lateral defect after removing a 250-g specimen that was inltrating ductal carcinoma. E: The medial defect was smaller ,with the 50-g specimen being benign. The resections were both performed through the standard Wise pattern margins. In order to preserve shape, she underwent an inferior pedicle breast reduction, removing an additional 50 g, and a similar contralateral breast reduction, removing 500 g from the left breast. F, G: She has preservation of shape and symmetry at 1 year following completion of radiation therapy.

Chapter 12 Reconstruction of Partial Mastectomy Defects

157

Figure 12.16. Thoracoepigastric ap. A: Presurgery. Front view illustrating direct access to the tumor bed, quadrantectomy including skin, and skin rotation ap based on the epigastric perforators. B: Postsurgery. Result after radiation on the right breast. The scar of the donor site disappears under the inframammary fold after advancement of upper abdominal skin. C: The natural breast shape is maintained.

survival, cosmesis, and appropriate conversion to a completion mastectomy if necessary. The latissimus dorsi (LD) musculocutaneous ap is a common local option for lateral, central, inferior, and even medial defects (Figs. 12.17 and 12.18) (19,26,27). It has excellent blood supply and provides both muscle for lling of glandular defects and skin for cutaneous deciencies. Avoiding a scar on the back can be achieved by harvesting the LD without skin through the lateral breast incision. The use of an endoscope can assist in raising the muscle (Fig. 12.19) (26). A deinnervated and radiated LD will undergo postoperative atrophy. To compensate for the expected loss in muscle volume, a ap much larger than the defect should be harvested, possibly preserving subscarpal fat on the muscle. A similar skin island to the classical LD musculocutaneous ap can be raised as a pedicled perforator ap either from the thoracodorsal or intercostal vessels. By sparing the underlying muscles or using perforator aps the donor-site morbidity has been reduced to the mini-

mum, with no seroma formation at the donor site (21,28). The thoracodorsal artery perforator (TDAP) ap can easily reach defects in the lateral, superolateral, and central regions of the breast. If no suitable perforators are found, the ap is easily converted to a muscle-sparing TDAP or muscle-sparing LD ap. The lateral intercostal artery perforator ap is another alternative to the TDAP ap for lateral and inferior breast defects. The lateral intercostal artery perforators are found at 2.7 to 3.5 cm from the anterior border of the LD muscle (29). The anterior intercostal artery perforator (AICAP) ap is similar to the random-designed thoracoepigastric skin ap. The skin paddle can be harvested as an AICAP ap. The AICAP is based on perforators originating from the intercostal vessels through the rectus abdominis or the external oblique muscles. Since it has a short pedicle, the AICAP ap is suitable to cover close defects that extend over the inferior or medial quadrants of the breast (35). The superior epigastric artery perforator (SEAP) ap is based

158

Section I Oncology and Oncoplastic Surgery

Figure 12.17. A, B: A 67-year-old woman with a history of stage


IV breast cancer previously underwent a right mastectomy with a transverse rectus abdominis myocutaneous ap reconstruction and a left breast amputation. Three years later she developed cutaneous metastasis in the left upper outer quadrant. C: Unable to complete chemotherapy, a wide excision and latissimus dorsi ap reconstruction was planned. D: The defect was in the upper outer quadrant. E: It was covered with a latissimus dorsi myocutaneous ap.

on perforators arising from the superior epigastric artery or its supercial branch (30). It has the same indications as the AICAP ap; however, the SEAP ap has longer pedicled and therefore it can cover more remote defects in the breast. Large medial defects are more difcult to reconstruct. The supercial inferior epigastric artery free ap has been described for this location (31,32). In situations such as

this one, or when the partial mastectomy defect is signicant with minimal residual breast tissue, a decision needs to be made whether to complete the mastectomy and perform total breast reconstruction for both cosmetic and oncologic reasons. Various other techniques have been described to ll partial mastectomy defects; however, these are currently less common.

Figure 12.18. AC: A 61-year-old female who previously had a breast reduction underwent partial mastectomy and radiation therapy for a lower pole breast cancer on the right side. D, E: The scar tissue was marked, and a latissimus dorsi skin island was drawn preoperatively. The deformity was resected, removing the involved retracted scar and covered with a latissimus dorsi myocutaneous ap. FH: The skin replacement improved the contour in the lower pole, and a contralateral mastopexy was performed for symmetry.

159

160

Section I Oncology and Oncoplastic Surgery

Figure 12.19. A, B: A 34-year-old woman who had previously


had a breast reduction and subsequent required a partial mastectomy in the upper quadrant. Initial margins were positive, and she was taken back for reexcision. CE: Once conrmation of negative margins was obtained following the second resection she already had a signicant contour deformity. F, G: In order to ll the volume void, a latissimus dorsi myofascial ap was harvested through a minimally invasive approach and transferred into the defect. (continued )

Chapter 12 Reconstruction of Partial Mastectomy Defects

161

Figure 12.19. (Continued ) H, I: Her shape and symmetry are preserved 6 months postoperatively. (From:
Partial Breast Reconstruction: Techniques in Oncoplastic Surgery, Eds. A. Losken, M. Hamdi, QMP, 2009.)

They include abdominal adipofascial aps, omental aps, and autologous fat injections (3335).

TIMING OF PARTIAL BREAST RECONSTRUCTION


Partial breast reconstruction can be performed at the time of mastectomy (immediate reconstruction), a few weeks following resection and before irradiation therapy (delayed-immediate reconstruction), or years after radiation therapy (delayed reconstruction). IMMEDIATE RECONSTRUCTION When partial breast reconstruction is indicated for any of the aforementioned reasons, then it is our preference to perform the reconstruction prior to breast irradiation. It is easier to perform volume displacement techniques to reshape a partial defect in a breast that is not contracted or brosed as is often the case following radiation therapy. Complication rates are lower when performing these parenchymal reshaping procedures prior to radiation therapy (17). The main disadvantage with immediate reconstruction is the potential for positive margins. Most series report a positive margin rate of 5% to 10% following oncoplastic resection, and rather than defer the reconstruction in every patient, it is preferable to select those patients at increased risk of positive margins and conrm margin status. DELAYED-IMMEDIATE RECONSTRUCTION Reconstruction is deferred for a few days until nal margin status has been conrmed. This was essentially proposed to alleviate the concerns of potential positive margins in some patients while still maintaining the benets of reconstruction prior to radiation therapy. The delayed-immediate approach is useful in patients with an increased potential for positive margins in whom reconstruction is desired or in patients where intraoperative concern exists. Such women at increased risk of positive margins included those of younger age ( 40 years old) or with extensive ductal carcinoma in situ, high grade, history of neoadjuvant chemother-

apy, inltrating lobular carcinoma, or Her2/neu positivity (13,36,37). The main disadvantage is the need for a secondary procedure, which might be unnecessary in the majority of cases. When a ap reconstruction is required, we prefer to conrm nal margin status prior to partial breast reconstruction. DELAYED RECONSTRUCTION The initial literature on partial breast reconstruction discussed the repair of BCT deformities in women years after irradiation (38). Although delayed reconstruction has the benets of clear margins and a time of recurrence-free status, the major disadvantage is that operating on a surgically scarred and already irradiated breast increases the risk of complications. Similar techniques are employed as in delayed reconstruction; however, they are associated with higher complication rates (42% vs. 26%) and worse cosmetic outcome (17). Parenchymal remodeling and reduction techniques following radiation therapy result in higher complication rates, and the need for ap reconstruction becomes more common.

MANAGEMENT OF MARGINS
The importance of negative margins in BCT cannot be overstated and has been associated as a factor for increased local recurrence, especially in younger patients (39). Oncologic principles should be applied with equal stringency. This becomes even more critical when reconstructive procedures have been performed since positive margins on final pathology are potentially complicated by altered architecture or elimination of a potential reconstructive option. Careful attention to patient selection and margin status should be performed, and every attempt should be made to ensure negative margins. Preoperative breast imaging (magnetic resonance imaging [MRI], ultrasound, or mammography) is helpful in determining the extent of the disease and guiding the necessary resection and should be employed judiciously when indicated. An imaging study showed that tumor size was underestimated 14% by mammography and 18% by ultrasound, whereas MRI showed no difference when compared to the

162

Section I Oncology and Oncoplastic Surgery

pathologic specimen (40). Wire identication and bracketing wires placed preoperatively will localize the extent of resection (41). Intraoperative margin assessment requires multidisciplinary coordination among the surgeons, the pathologist, and the radiologist. Multicolored inking kits have proven to be more accurate than traditional stitch markings (42), especially for the more complex designed oncoplastic specimens. Additional intraoperative conrmatory procedures include gross examination, radiography of the specimen, intraoperative frozen sections for invasive cancer, and touch cytology. Separate cavity margins set at the time of lumpectomy signicantly reduce the need for reexcision. Cao et al. demonstrated that nal margin status was negative in 60% of patients with positive margins on initial resection (43). Rainsbury established a one-stage approach in which bed biopsies are taken from the cavity and subareolar region and sent for frozen section. The entire cavity is then inked and sent as a shave specimen for formal histology (27). If tumor is still present in the second set of biopsies, then a mastectomy is indicated. Although data are limited, some researchers have proposed that the positive margin rate following oncoplastic resections should be lower, given the ability to perform a generous resection. Oncoplastic resections in some series have been greater than 200 g, compared to institutional norms of about 40 to 50 g using lumpectomy alone (13,44). This does not include the additional glandular excisions necessary to achieve symmetry with the reduced contralateral breast in patients with macromastia. Kaur et al. demonstrated an oncologic benet in a comparative study in which positive margins were identied in 16% of breast cancer patients who had the oncoplastic approach versus 43% in patients with quadrantectomy (45). Comparisons in the literature are difcult, given the varying institutional denitions of what constitutes a positive margin; however, positive margin rates in most oncoplastic series range from 5% to 10% (13,17,45) compared to the larger BCT series of 10% to 15% (46,47). Placement of titanium perimeter clips to outline the lumpectomy cavity will guide the radiation therapy with postoperative tumor boost volume during teletherapy (external beam radiation). Communication is necessary between the oncologist and the surgeons especially when glandular remodeling has been performed. These clips will also assist in postoperative surveillance.

BCT alone (48). Although the qualitative mammographic ndings were similar in the two groups over the average 6-year follow-up, there was a slight trend toward longer times to mammographic stability in the oncoplastic reduction group (25.6 months vs. 21.2 months in the BCT alone group). This means that it might take the oncoplastic reduction patients slightly longer to reach the point where any change in mammographic ndings might be suspicious for malignancy. An accurate interpretation requires familiarity with these temporal changes, and mammograms should be compared over time. These data need to be taken into consideration when designing the most appropriate surveillance programs for these patients. Mammographic ndings following myocutaneous ap reconstructions have also been evaluated and will typically show areas of radiolucency consistent with a brofatty component in most aps (38,49). Microcalcications and areas of fat necrosis are easily identied, and no interference in postoperative surveillance has been demonstrated. Other imaging techniques, such as ultrasound and MRI, will likely become more popular as technology improves. Although routine tissue sampling is not recommended for screening, any clinical concern necessitates ne needle aspiration, core needle biopsy, or surgical biopsy to rule out malignancy. Patients who undergo partial breast reconstruction are expected to have an increase in the amount of tissue sampling requirements, as demonstrated in our series (53% in the oncoplastic group compared to 18% in the BCT-alone group over an average of 7 years). Although these are typically benign, additional scarring from the reconstruction might raise clinical suspicion, which is why more biopsies are expected in patients who undergo partial breast reconstruction.

COMPLICATIONS AND OUTCOMES


It is important that complications resulting from oncoplastic techniques do not interfere with the initiation of adjuvant therapy. Careful selection of surgical technique, appropriate patient selection, and meticulous execution will minimize the incidence of postoperative complications. Additional procedures will invariably increase complications; however, most of these are minor. Some larger series with volume displacement techniques report complications such as delayed wound healing (3% to 15%), fat necrosis (3% to 10%), and infection (1% to 5%) (13,17,16). Overall complications following volume replacement techniques are slightly higher (range 2% to 77%), and this is likely due to the addition of donor-site complications and potential ap loss issues (19,26,27). Delayed complications with the oncoplastic approach include breast brosis and asymmetry. Although the goal of partial breast reconstruction is to prevent an unfavorable cosmetic result, this approach cannot prevent or reverse the effects of radiation therapy. Since these effects will persist, the assessment of shape and symmetry needs to be made in the context of long-term considerations. However, with partial reconstruction shape is typically preserved and it is easier to adjust the contralateral side secondarily if necessary than reconstruct a radiated BCT deformity. Asgeirsson et al. reviewed numerous series with intermediate follow-up and demonstrated cosmetic failure rates of 0% to 18% (50). Local recurrence is another important outcome that needs to be evaluated in the oncoplastic patient. Most reviews in the literature are of intermediate follow-up (up to 4.5 years), with local recurrence rates varying from 0% to 1.8% per year (50).

SURVEILLANCE
One main concern with partial breast reconstruction is that it might impair the ability to screen and detect recurrent breast cancer. Some fear that glandular rearrangement, additional scarring, and the disruption of architecture might alter the potential patterns of local recurrence of the ability to screen and detect these lesions. Although this is a valid concern, adherence to appropriate surveillance and cross-specialty communication will reduce this as an issue. The three main tools when it comes to postoperative surveillance include the physical examination, radiologic imaging, and tissue sampling. It is important that all members of the team are aware of the various surgical components since differences in presentation might exist, depending on the type and technique of reconstruction. We recently demonstrated that mammography following partial breast reconstruction using reduction techniques was just as sensitive as a screening tool when compared to patients with

Chapter 12 Reconstruction of Partial Mastectomy Defects

163

Actuarial 5-year local recurrence rates range from 8.5% to 9.4% (41). Longer-term studies are required.

CONCLUSION
The details differ depending on whether one is dealing with lumpectomy or quadrantectomy defects or whether a two-team or single-surgeon approach is used; however, the principles are the same. A simplied reconstruction outline is proposed (see Fig. 12.9). The benets of using the oncoplastic approach with breast conservation therapy have been well demonstrated and will continue to gain popularity and acceptance in the future. The options for women with breast cancer are numerous, and this approach provides an additional, often favorable one. We need to critically evaluate results, measuring functional, oncologic, and aesthetic outcomes in an attempt to establish safe and effective practice guidelines to maximize oncologic safety. EDITORIAL COMMENTS Dr. Losken provides us with an updated look at the subject of oncoplastic surgery for reconstruction and optimization of partial mastectomy procedures for the treatment of breast cancer coupled with radiation therapy. This is a relatively young eld, and successive publications on these procedures continue to describe new and more options. In addition, the evidence continues to accumulate that these procedures have value in terms of producing improved cosmetic outcomes without increasing the risk of local breast cancer recurrence. If anything, the availability of oncoplastic options expands the number of patients who might be candidates for breast conservation therapy and also increases the possible margins and quantity of tissue that might be resected. It is our opinion that, as the options expand and the complexity of techniques becomes more sophisticated, the arguments for a collaborative approach become more powerful. Dr. Losken describes multiple techniques, including subtle variations. The techniques described here are more complex than most plastic surgeons employ in their standard plastic surgery breast practice. Being able to provide state-of-the-art solutions to the great number of presentations after tumorectomy is increasingly going to require the skills of a surgeon or team of surgeons who are committed to staying on top of this subject. In our medical center, the philosophy of employing oncoplastic techniques has increasingly caught hold, leading to improved aesthetic and oncologic outcomes for women with breast cancer. S.L.S. Dr. Losken addresses one of the most talked about concepts in oncoplastic surgery: reconstruction of the partial mastectomy defect. This approach was rst popularized in Europe and has been slowly gaining acceptance in the United States. By classifying the defect and the reconstruction choices, he is able to devise an algorithm for these types of reconstructions. These operations are designer operations since every one must be unique to account for the myriad factors

that can affect outcome. It is quite clear that the best results will arise out of a thorough understanding of the breast cancer (location, size, prior therapy), attention to aesthetic principles, and consideration of the individuals body habitus and preferences. The surgeons caring for the patient must have a vision of what may be necessary oncologically and what may be possible aesthetically and communicate that to the patient. I appreciate many of the concepts Dr. Losken highlights in this chapter. First and foremost is attaining clear margins. There is nothing more disappointing than having a beautiful cosmetic result after an oncoplastic procedure, only to nd that a margin is positive. To this end, all strategies to decrease the positive margin rate should be employed. Preoperative magnetic resonance imaging, two-view specimen radiography, six-color ink marking of the specimen by the surgeon, intraoperative margin reexcision and perimeter clips are all valuable adjuncts. There will be ongoing attention given to oncoplastic surgery in the future and more developments as we incorporate new concepts, such as partial breast irradiation and intraoperative radiation, into the algorithm. S.C.W.

REFERENCES
1. Audretsch WP. Reconstruction of the partial mastectomy defect: classication and method. In: Spear SL, Willey SC, Robb GL, Hammond DC, Nahabedian MY, eds. Surgery of the Breast: Principles and Art. Philadelphia, PA: Lippincott Williams & Wilkins; 2006:179216. 2. Silverstein MJ, Lagios MD, Groshen S, et al. The inuence of margin width on local control of ductal carcinoma in situ of the breast. N Engl J Med 1999;340:14551461. 3. Veronesi U, Volteranni F, Luini A, et al. Quadrantectomy versus lumpectomy for small size breast cancer. Eur J Cancer 1990;26:671673. 4. Clough KB, Cuminet J, Fitoussi A, et al. Cosmetic sequelae after conservative treatment for breast cancer: classication and results of surgical correction. Ann Plast Surg 1998;41: 471481. 5. Brierly JD, Paterson IC, Lallemand RC, et al. The inuence of breast size on late radiation reaction following excision and radiotherapy for early breast cancer. Clin Oncol 1991;3:69. 6. Zierhut D, Flentje M, Frank C, et al. Conservative treatment of breast cancer: modied irradiation technique for women with large breasts. Radiother Oncol 1994;31:256261. 7. Clark K, Le MG, Sarrazin D, et al. Analysis of locoregional relapse in patients with early breast cancer treated by excision and radiotherapy: experience of the Institute GustaveRoussy. Int J Radiat Oncol Biol Phys 1985;11:137145. 8. Waljee JF, Hu ES, Newman LA, et al. Predictors of breast asymmetry after breast-conserving operation for breast cancer. Am Coll Surg 2008;206:274280. 9. Clough KB, Kroll SS, Audretsch W. An approach to the repair of partial mastectomy defects. Plast Reconstr Surg 1999;104(2):409. 10. Berrino P, Campora E, Santi P. Postquadrantectomy breast deformities: classication and techniques of surgical correction. Plast Reconstr Surg 1987;79(4):567572. 11. Losken A, Hamdi M, Partial breast reconstruction: current perspectives. Plast Reconstr Surg 2009;124(3):722736. 12. Anderson BO, Masetti R, Silverstein MJ. Oncoplastic approaches to partial mastectomy: an overview of volume replacement techniques. Lancet Oncol 2005;6(3):145157. 13. Losken A, Styblo TM, Carlson GW, et al. Management algorithm and outcome evaluation of partial mastectomy defects treated using reduction or mastopexy techniques. Ann Plast Surg 2007;59(3):235242. 14. Masetti R, Pirullo PG, Mango S, et al. Oncoplastic techniques in the conservative treatment of breast cancer. Breast Cancer 2000;7:276280. 15. Clough KB, Nos C, Salmon RJ, et al. Conservative treatment of breast cancer by mammaplasty and irradiation: a new approach to lower quadrant tumors. Plast Recon Surg 1995;96(2):363370. 16. Munhoz AM, Montag E, Arruda EG, et al. Critical analysis of reduction mammaplasty techniques in combination with conservative breast surgery for early breast cancer treatment. Plast Reconstr Surg 2006;117(4):10911107. 17. Kronowitz SJ, Feledy JA, Hunt KK, et al. Determining the optimal approach to breast reconstruction after partial mastectomy. Plast Reconstr Surg 2006;117(1):111. 18. Kronowitz SJ, Kuerer HM, Buchholz TA. A management algorithm and practical oncoplastic surgical techniques for repairing partial mastectomy defects. Plast Reconstr Surg 2009;122:16311647. 19. Munhoz A, Montag E, Fels KW, et al. Outcome analysis of breast-conservation surgery and immediate latissimus dorsi ap reconstruction in patients with T1 to T2 breast cancer. Plast Reconstr Surg 2005;116(3):741752.

164

Section I Oncology and Oncoplastic Surgery


37. Song HM, Styblo TM, Carlson GW, et al. The use of oncoplastic reduction techniques to reconstruct partial mastectomy defects in women with ductal carcinoma in situ. Breast J 2010;Jan 19 [Epub ahead of print]. 38. Slavin SA, Love SM, Sandowsky NL. Reconstruction of the radiated partial mastectomy defect with autologous tissues. Plast Reconstr Surg 1992;90:854. 39. Leong C, Boyages J, Jayasinghe UW, et al. Effect of margins on ipsilateral breast tumor recurrence after breast conservation therapy for lymph node-negative breast carcinoma. Cancer 2004;200(9):18231832. 40. Boetes C, Mus RD, Holland R, et al. Breast tumors: comparative accuracy of MR imaging relative to mammography and US for demonstrating extent. Radiology 1995;197: 743747. 41. Liberman L, Kaplan J, Van Zee KJ, et al. Bracketing wires for preoperative breast needle localization. AJR Am J Roentgenol 2001;177:565572. 42. Neuschatz AC, DiPetrillo T, Steinhoff M, et al. The value of lumpectomy margin assessment as a predictor of residual tumor burden in ductal carcinoma in situ of the breast. Cancer 2002;94:19171924. 43. Cao, D, Lin C, Woo SH, et al. Separate cavity margin sampling at the time of initial breast lumpectomy signicantly reduces the need for re-excision. Am J Surg Pathol 2005;29(12): 16251632. 44. Clough KB, Lewis JS, Couturaud B, et al. Oncoplastic techniques allow extensive resections for breast-conserving therapy of breast cancer. Ann Surg 2003;237(1):2634. 45. Kaur N, Petit JY, Rietjens M, et al. Comparative study of surgical margins in oncoplastic surgery and quadrantectomy in breast cancer. Ann Surg Oncol 2005;12(7):539545. 46. Fisher B, Anderson S, Bryant J, et al. Twenty-year follow up: a randomized trial comparing total mastectomy, lumpectomy, and lumpectomy plus irradiation of the treatment of invasive breast cancer. N Engl J Med 2002;347:12331241. 47. Veronesi U, Casinelly N, Mariani L, et al. Twenty-year follow-up of a randomized study comparing breast conserving surgery with radical mastectomy for early breast cancer. N Engl J Med 2002;347:12271232. 48. Losken A, Schaefer TG, Newell M, et al. The impact of partial breast reconstruction using reduction techniques on post-operative cancer surveillance. Plast Reconstr Surg 2009; 124(1):917. 49. Monticciolo DL, Ross D, Bostwick J III, et al. Autologous breast reconstruction with endoscopic latissimus dorsi musculosubcutaneous aps in patients choosing breast-conserving therapy: mammographic appearance. Am J Roentgenol 1997;167(2):385389. 50. Asgeirsson KS, Rasheed T, McCulley SJ, et al. Oncological and cosmetic outcomes of oncoplastic breast conserving surgery. Eur J Surg Oncol 2005;31(8):817823.

20. Munhoz AM, Montag E, Arruda EG, et al. The role of the lateral thoracodorsal fasciocutaneous ap in immediate conservative breast surgery reconstruction. Plast Reconstr Surg 2006;117:1699. 21. Hamdi M, Van Landuyt, Monstrey S, et al. Pedicled perforator aps in breast reconstruction: a new concept. Br J Plast Surg 2004;57(6):531539. 22. Chung TL, Schnaper L, Silverman R, et al. A novel reconstructive technique following central lumpectomy. Plast Reconstr Surg 2006;118(1):2327. 23. McCulley SJ, Dourani P, Macmillan RD. Therapeutic mammaplasty for centrally located breast tumors. Plast Reconstr Surg 2006;117(2):366373. 24. Schoeller T, Huemer GM. Immediate reconstruction of the nipple/areolar complex in oncoplastic surgery after central lumpectomy. Ann Plast Surg 2006;57(6):611615. 25. Petit JY, De Lorenzi F, Rietjens M, et al. Technical tricks to improve the cosmetic results of breast-conserving treatment. Breast 2007;16(1):1316. 26. Losken A, Schaefer T, Carlson GW, et al. Immediate endoscopic latissimus dorsi ap: risk or benet in reconstructing partial mastectomy defects. Ann Plast Surg 2004;53(1):15. 27. Rainsbury RM. Breast sparing reconstruction with latissimus dorsi miniaps. Eur J Surg Oncol 2002;28:891895. 28. Hamdi M, Van Landuyt K, de Frene B, et al. The versatility of the inter-costal artery perforator (ICAP) aps. J Plast Reconstr Aesthet Surg 2006;59(6):644652. 29. Hamdi M, Spano A, Van Landuyt K, et al. The lateral intercostal artery perforators: an anatomical study and functional application in breast surgery. Plast Reconstr Surg 2008;121(2):389396. 30. Hamdi M, Van Landuyt K, Ulens S, et al. Clinical applications of the superior epigastric artery perforator (SEAP) ap: anatomical studies and preoperative perforator mapping with multidetector CT. J Plast Reconstr Aesthet Surg 2009;62(9):11271134. 31. Rizzuto RP, Allen RJ. Reconstruction of a partial mastectomy defect with the supercial inferior epigastric artery (SIEA) ap. J Reconstr Microsurg 2004;20(6):441445. 32. Spiegel AJ, Khan FN. An intraoperative algorithm of use of the SIEA ap for breast reconstruction. Plast Reconstr Surg 2007;120(6):14501459. 33. Zaha H, Inamine S, Naito T, et al. Laparoscopically harvested omental ap for immediate breast reconstruction. Am J Surg 2007;192:789791. 34. Ogawa T, Hanamura N, Yamashita M, et al. Usefulness of breast volume replacement using an inframammary adipofascial ap after breast conservation therapy. Am J Surg 2007;193:514518. 35. Kitamura K, Kajitani K, Hedrick M, et al. Stem cell augmented reconstruction: a new hope for reconstruction after breast conservation therapy. Breast Cancer Res Treat 2007;106(suppl 1):238. 36. Miller AR, Brandao G, Prihoda TJ, et al. Positive margins following surgical resection of breast carcinoma: analysis of pathologic correlates. Am J Surg 2004;187(5):647650.

CHAPTER

13
Special Problems in the Treatment and Reconstruction of Breast Cancer
INTRODUCTION
The management of women with breast cancer continues to evolve, and along with that reconstructive standards and expectations are increasing. Newer techniques and newer technology have become essential to reduce potential morbidities and improve cosmetic results. We are now seeing a greater diversity of potential candidates for reconstruction and are subsequently reconstructing more patients with the entire spectrum of breast size, shape, and body habitus. Women with very small, ptotic, or very large breasts pose unique challenges throughout the treatment process from initial workup and diagnosis of the breast cancer to the completion of the reconstructive process. The treatment and reconstruction of breast cancer in these situations will be discussed in this chapter.

Albert Losken

THIN PATIENTS
SMALL BREASTS Breast reconstruction in thin women with small breasts poses unique challenges in that the available autologous donor tissue is often limited, and matching a contralateral small breast is difficult. These patients are typically younger and have active lifestyles. As part of the preoperative discussion it is important to address the patients desires for her ideal breast size prior to discussing the reconstructive procedure since an augmented contralateral breast would increase the reconstructive options.

Autologous Tissue Reconstruction


In patients who wish to match a small contralateral breast, limitations exist in terms of donor sites. If a small lower abdominal panniculus exists, free tissue transfer from the abdomen becomes an option. Generally 200 to 300 g of tissue can be harvested from a relatively thin abdomen, which is often enough to match the opposite side. Preoperative marking of the inframammary fold is critical, as this is often obscured in women with small breasts, especially following mastectomy. The upper transverse rectus abdominus myocutaneous (TRAM) ap incision is extended laterally, and ap dissection is beveled away from the ap to incorporate adjacent subcutaneous tissue for added bulk. In an attempt to preserve as much volume as possible, more zones (I to IV) might be recruited, stressing the importance of maximizing blood ow and selecting those patients without additional morbidities such as abdominal scars and smoking effects. Attempted closure should always be performed in the semi-Fowler position prior to committing on ap size. Making the ap too wide in an attempt to

adequately ll the pocket without considering tension on the donor-site closure will cause unnecessary problems with donor morbidity. Implants can always be added at a later stage rather than attempting to remove too much tissue (Fig. 13.1). The extended free TRAM recruits the lateral extensions, which even in thin patients can provide sufcient volume and projection for bilateral reconstructions (1). The free muscle-sparing TRAM is often the procedure of choice in these patients with small breasts, given the superior ap perfusion, as well the preservation of the inframammary fold. Pedicled TRAM aps are not ideal, in that disruption of the inframammary fold (IMF) in women with small breasts often leads to lack of lower pole denition. Tunneling a pedicled ap either ipsilateral or contralateral into a small breast pocket will often obscure the inframammary fold. Secondary recontouring of the IMF at the time of nipple reconstruction is difcult. Supercial inferior epigastric artery aps provide minimal donor morbidity and are an excellent option when the vessels are large enough (2). When the abdominal tissue is in position, the edges can be folded in a transverse orientation to autoaugment breast size, especially in the smaller mastectomy pocket. If the pocket is wide (i.e., following axillary node sampling), shaping sutures are often necessary to close the pocket or appropriately position the ap for maximal shape and projection. In women who have very tall, slender, and narrow chests, longitudinal or oblique orientation of the ap will provide better shape without loss of superior fullness. Even thin patients occasionally have sufcient back tissue to be candidates for an extended autologous latissimus dorsi ap reconstruction (Fig. 13.2). There can be some fatty deposits over the trapezius muscle and above the iliac crest that provide bulk to the ap. The skin island is dissected down to Scarpas fascia, and subfascial fat is kept on the muscle for added volume. Preservation of the subdermal plexus (with 1 cm of layer of fat) is important to provide blood supply to the remaining skin once the perforating vasculature of the latissimus has been removed. In thin patients, the muscle pedicle is often noticeable, making the breast appear wide. The humeral insertion is taken down, and sub-Scarpa fat is not preserved in the axilla to prevent axillary fullness. Attempts to minimize seroma formation in thin patients include using 10-mm Blake drains for 2 to 3 weeks, using resorbable quilting sutures from the skin aps to the chest wall, and possibly spraying the cavity with Tisseel spray prior to closure. This has reduced the postoperative drainage in patients at our institution. Autologous fat injections can augment the breast minimally at the second stage if necessary (see Fig. 13.2). The superior gluteal ap, although technically more difcult and less forgiving, is a reasonable alternative in thin patients who are not TRAM ap candidates. It can provide descent volume and projection (3). The transverse myocutaneous gracilis

165

166

Section I Oncology and Oncoplastic Surgery

Figure 13.1. A: Preoperative view of a 39-year-old woman with right-sided breast cancer who desired transverse rectus abdominus myocutaneous (TRAM) ap breast reconstruction. B: Following bilateral skin-sparing mastectomy and immediate TRAM ap breast reconstruction, she had inadequate ll-in the upper pole. C: Size and shape were restored by the placement of bilateral subpectoral smooth saline implants at the time of nipple reconstruction.

Chapter 13 Special Problems in the Treatment and Reconstruction of Breast Cancer

167

Figure 13.2. A, B: A 36-year-old woman with left breast cancer


who did not desire implants and had insufcient abdominal tissue to match her right breast. C: She underwent a skin-sparing mastectomy with immediate autologous latissimus dorsi ap reconstruction. D, E: Her secondary procedures included nipple reconstruction and injection of 40 cc of fat into the outer quadrant for symmetry in contour and shape. She is shown 1 year following nipple-areolar tattoo.

muscle ap is another option in women without sufcient abdominal fat that has been successfully used for postmastectomy breast reconstruction (4). Bilateral mastectomies in thin patients with small breasts are often more difcult to reconstruct using abdominal aps, given lack of sufcient tissue, especially in those patients with a relatively wide chest wall and some breast ptosis. Bilateral gluteal aps or autologous latissimus dorsi aps can be used when donor tissue is available.

Implant Reconstruction
Implant reconstruction is possible as a single-stage procedure if the patients breasts are small (A or small B cup), round, or in bilateral reconstructions. It is important to mark the inframammary fold bilaterally as this will assist with positioning of the implant. Fold asymmetry in the small, nonptotic breast will be noticeable postoperatively. Although round implants, when relatively small, will often provide decent shape, anatomic

168

Section I Oncology and Oncoplastic Surgery

implants can provide more lower pole fullness if this is required to match the opposite side (5). The submuscular pocket is created from the lateral border of the pectoralis major muscle. The serratus anterior is also elevated for better implant coverage and prevention of lateral displacement if an axillary dissection is performed or if the mastectomy defect extends laterally. The pectoralis muscle is released inferiorly to allow lower pole projection of the implant. An acellular dermal matrix is sutured to the IMF inferiorly and the pectoralis muscle superiorly for more lower pole coverage and better projection. The skin is then closed in layers over a drain either horizontally or in a purse-string fashion. A contralateral procedure is not necessary in breasts with minimal ptosis and if the patient has no desire to have larger breasts. In women with small breasts and moderate ptosis (greater than 2 cm), a contralateral mastopexy or mastopexy/augmentation is often required to ensure symmetry. A two-staged expander reconstruction is also an excellent option using a similar technique as mentioned previously and is often preferred in patients with small breasts where skin tension is a concern postoperatively. This will allow controlled postoperative expansion to the desired size, with secondary implant placement. Textured anatomic expanders with integrated valves have demonstrated less capsular contracture and valve dysfunction and provide lower pole expansion. An initial amount of saline is added to the expanders intraoperatively depending on the status of the skin aps and muscle tension. Expansion is then started in the ofce 2 weeks postoperatively and progressed as tolerated. Implant exchange with a round or contoured silicone implant is performed secondarily.

Autologous Fat Transfer


Although under investigation, breast reconstruction using autologous fat injections might prove to be very useful in women with small breasts where only a limited amount of fat would be required to match the opposite side. It has been a very useful option as an adjunct to other reconstructions, especially in thin patients, where ap volume is often limited.

required to augment the breast size. This can be placed beneath the abdominal ap or the latissimus dorsi ap (9). The implant contributes less to the overall size and shape of the breast with TRAM ap coverage. The subcutaneous fat on the TRAM closely resembles that of native breast tissue and will not atrophy with time; instead, it uctuates in size and shape with the patients weight and opposite breast. Flap compromise following free TRAM ap coverage of implants has not been demonstrated; however, seroma cavities can occur (10,11). Coverage of the implant with a latissimus dorsi myocutaneous ap will rely more on the implant for size and shape as muscle atrophy generally occurs. Implants can be placed beneath the pectoralis muscle for better muscular coverage, especially in thin patients with thin skin. Overzealous size augmentation following SSM is fraught with difculties related to wound dehiscence and native breast skin ap necrosis. If moderate enlargements were desired, it would be safer to use tissue expanders and or increase the size of the skin island. Placement of the implant can also be performed secondarily if radiation therapy is anticipated or if the contralateral procedure is delayed. Management of the contralateral breast in the unilateral reconstructions for thin patients desiring larger breasts will typically require implant augmentation with or without mastopexy. This can be performed at the time of reconstruction or as a secondary procedure, depending on personal preference. I prefer to perform the symmetry procedures at the time of reconstruction, as it is easier to match the adjusted opposite breast with the reconstruction than vice versa unless radiation therapy is required. In thin patients who already have large breasts, the aforementioned techniques are also applicable. Implants can be added to autologous tissue if size maintenance is desired; otherwise contralateral breast reduction will allow the reconstruction of a smaller breast, which might make pure autologous tissue reconstruction possible.

Implant Reconstruction
Implant reconstruction is possible if the opposite breast is augmented or round and full with minimal ptosis. It is more difcult to match a large, ptotic contralateral breast with implants alone. Even following breast reduction procedures, symmetry with implants alone in thin patients with large breasts is difcult to obtain, especially long term, as the breasts will age differently.

Breast Conservation Therapy


Breast preservation in women with small breasts who require a resection over 20% of their breast volume will often result in unfavorable cosmesis. Options include local ap reconstruction using oncoplastic techniques if breast conservation therapy (BCT) is desired (6,7) or skin-sparing mastectomy (SSM) and immediate reconstruction. Reconstructing the lumpectomy defect using autologous fat grafting, which is processed to create a mixture of concentrated fat cells and stem cells, is a technique that is under investigation (8). LARGE BREASTS The reconstructive options in thin patients with small breasts who desire larger breasts or thin patients with large breasts involve the addition of implants and the need for a contralateral procedure in unilateral reconstructions.

OBESE PATIENTS
Obesity increases the risk of breast cancer and is associated with advanced-stage breast cancer and poorer prognosis (12,13). We are subsequently seeing more obese women requesting reconstruction. Reconstructive options in obese patients are limited not by available tissue but rather by the inherent risks associated with surgical complications. Mastectomy with axillary node dissection alone in the obese patient is associated with increased risk of seroma formation and wound infection (14). It is important that the surgeon discuss the risks and benets of the surgery preoperatively. Obese patients have an increased incidence of pulmonary, thrombotic, anesthetic, infectious, and metabolic perioperative complications (15) and are often considered poor candidates for breast reconstruction. These patients are often disappointed with their overall appearance and subsequently dissatised with their results. Patient expectations, limitations of the

Autologous Reconstruction
The same autologous options do exist with the aforementioned limitations. However, the addition of an implant is often

Chapter 13 Special Problems in the Treatment and Reconstruction of Breast Cancer

169

surgery, and the need for additional procedures should all be discussed. Given the presence of one risk factor already, stringent patient selection and evaluation of additional risk factors are important to minimize postoperative complications. SMALL BREASTS Obese patients with small breasts who desire reconstruction are best managed with the standard periareolar skin-sparing mastectomy incision. Lateral extension can increase exposure if required, especially in women with wide breasts.

Autologous Reconstruction
Autologous reconstruction in obese patients is not limited by the amount of available tissue but by the risk of donor-site and breast-related complications. The extended latissimus dorsi ap is often one of the safer procedures and is ideal for obese patients with small breasts (Fig. 13.3). The additional fat beneath Scarpas fascia will provide enough bulk for a totally autologous reconstruction (16). This technique is best suited for obese patients with additional risk factors, for whom the TRAM ap is

not a good choice, and those with greater than 2 cm of back fat by pinch test. (17,18). An elliptical, crescent, or eur-de-lis skin island pattern is drawn on top of the latissimus dorsi muscle centered over the fat roll of the back. We typically use a crescent shape that corresponds to the amount of skin required and the size of the breast to be reconstructed. The dissection is then carried above Scarpas fascia leaving subfascial bulk on top of the latissimus muscle. From 200 to 300 cc volume equivalent can be added, depending on the body habitus of the patient. The ap is then transferred into the pocket and position to provide optimal shape. The majority of the skin island is deepithelialized and placed inferiorly to emphasize lower pole fullness and the ptotic shape of the breast. The ap can be shaped as a U shape to ensure lower pole fullness. The donor site is closed as described previously. The main disadvantage is the donor-site morbidity with the risk of seroma and prolonged drainage. The abdominal ap techniques can also provide sufcient volume to match a small breast; however, the potential for donor-site morbidity is not insignicant in obese patients (19). Hartrampf in 1988 concluded that in certain high-risk patients, specically obese and overweight patients, the complication rates with the TRAM ap were unacceptably high (20). In a recent

Figure 13.3. A, B: A 63-year-old woman with a body mass index of 31 who had signicant breast asymmetry following breast biopsy many years ago from the left side. C: She underwent a right mastectomy through a generous elliptical incision, followed by an extended autologous latissimus dorsi breast reconstruction. SubScarpa fat was included for volume. D: At the time of nipple reconstruction, she had 85 cc of fat injected into the upper pole for further volume augmentation and shape improvement.

170

Section I Oncology and Oncoplastic Surgery

series of pedicled TRAM aps, the complication rates were signicantly higher in obese patients that the authors cautioned against the use of TRAM aps in patients whose body mass index (BMI) is greater than 30 (21). Although the actual ap tends to be relatively reliable since only a small portion (zone 1) is typically required, the abdominal tissue is often not a rst choice when only a small amount of tissue is required. Caution should be taken in obese patients with intraabdominal girth since the actual amount of subcutaneous tissue above the rectus muscle is minimal and morbidity is increased. Numerous authors have demonstrated obesity as a signicant risk factor for complications following TRAM ap reconstructions (19,22,23). Obesity has been associated with increased fat necrosis, partial ap loss, and infection. Guidelines exist based on ideal body weight or BMI. Kroll and Netscher demonstrated a linear correlation between complication rate and BMI (19). As a rule, patients with BMI over 50 are not considered candidates for pedicled TRAM ap procedures. Obese patients with multiple additional morbidities are poor TRAM ap candidates. However, obesity alone should not prevent the surgeon from offering pedicled or free TRAM ap reconstruction. Careful use of these procedures can produce reproducible results with an acceptable rate of postoperative complications. The perfusion or reliability of the TRAM ap can be improved by free TRAM ap or surgical delay. The free TRAM aps enhanced vascular supply has allowed the liberal use of this ap in obese patients. However, even free TRAMs in obese patients have a signicantly higher total ap loss, hematoma, seroma, infection, and hernia rate than those in nonobese patients (17). The DIEP ap is considered preferable over the pedicled TRAM and the free TRAM in overweight and obese patients, given a reduced incidence of abdominal bulge (24). Abdominal wall perforators are usually large in obese patients, allowing the use of perforator aps such as the DIEP ap to be used as an alternative choice.

The Wise pattern will assist with reshaping the large breast and preventing the more box-type look if closed in a horizontal fashion. However, wound healing problems are not infrequent on the mastectomy side, as the skin aps are often thin, leading to necrosis at the T junction (25). Deepithelializing the lower mastectomy skin aps at the inframammary fold rather than excising skin will augment the blood ow to the skin and minimize wound healing issues. This allows secondary healing even in the face of mastectomy ap skin necrosis, especially when implant reconstruction is performed.

Autologous Reconstruction
Although obesity is considered a relative contraindication for some autologous tissue reconstructions, this is usually the most reliable way to match the often soft and ptotic opposite breast. Obesity is a strong predictor of complications in any type of autologous reconstruction (26). Use of the latissimus dorsi flap is often safer from a donor-site point of view. An implant is often required for added volume even with the extended autologous ap and a moderate reduction on the contralateral side. Abdominal aps are associated with some donor-site morbidity as discussed previously; however, they are often required, given the amount of tissue that is required to match even a reduced contralateral breast. Various techniques have been suggested to increase the reliability of these aps to accommodate volume requirements and minimize morbidity in obese patients. Some have advocated vascular delay of the TRAM ap in obese patients as a way of improving reliability and safety of the procedure in these patients in centers where microvascular expertise is not readily available (27). The midabdominal pedicled TRAM ap is another option that is felt to increases the reliability of the skin island and allows a larger area to be used to match a larger contralateral breast. Since the rectus muscle is divided above the arcuate line, the donor morbidity is minimized with this technique, making it a reasonable option even in morbidly obese patients (28). Supercharging the TRAM ap has been described to improve the vascularity of the TRAM ap and minimize breast complications in the obese population; however, donor-site morbidity remains (29). If a smaller, yet more reliable ap is the only option, then the breast should be shaped appropriately with the available volume with the plan to augment the breast at a later stage using an implant. The fat in obese patients is poorly vascularized and is at risk for developing fat necrosis, especially below Scarpas fascia. During elevation of the abdominal skin to the costal margin, lateral dissection should be minimized to ensure lateral perforators. This, along with resection of sub-Scarpas fascia on the abdominal wall, will minimize donor-site fat necrosis and improve wound healing. Abdominal tissue in obese patients is often thick and noncompliant, which interferes with the shaping process. Generous resection of the sub-Scarpa fat on the actual TRAM ap will preserve vascularity, help minimize fat necrosis, and improve shape by making breast contours more natural (Fig. 13.5). Thinning of the ap should be performed prior to tunneling, to minimize the size of the IMF tunnel. If the tunnel is too large, it will drop the IMF, affecting nal symmetry. Closure of the rectus fascia is important, given the higher incidence of abdominal bulge or hernias. Inlay Prolene mesh should be used if closure is too tight. Drains are typically left in for 2 to 3 weeks to minimize seroma formation.

Implant Reconstruction
Obese patients with small breasts often have a moderate amount of ptosis and relatively wide breasts. Implant reconstruction is reasonable in bilateral reconstructions or if the patient is old or has multiple risk factors that make autologous reconstruction contraindicated. It is important that the patient realize that the goal is to provide some balance in a brassiere and that the reconstructed breast is often at and symmetry with a small, wide, and ptotic contralateral breast is difficult to achieve. Whether performed as a one- or a twostage reconstruction, it is important to control the pocket and dene the breast laterally with either allograft placement or elevation of the serratus muscle; otherwise the potential for implant malposition is high. LARGE BREASTS Obese patients with large, ptotic breasts pose several additional challenges. Reconstructing a breast that is smaller, whether with an implant or a ap, in a larger breast pocket is challenging. A contralateral procedure is invariably required in unilateral reconstructions, with reduction of skin and or breast parenchyma on both sides (Fig. 13.4). This is often done through a Wise keyhole, inverted T, or a vertical pattern. In order to ensure symmetry in unilateral reconstructions, it is tempting to perform the identical skin takeout on both sides.

Chapter 13 Special Problems in the Treatment and Reconstruction of Breast Cancer

171

Figure 13.4. A: A 59-year-old woman (weight 184 pounds, height 5 foot, 1 inch) with a left-sided lobular
carcinoma, moderate build with bilateral macromastia, and grade IV ptosis. B: Wise pattern reduction markings are drawn preoperatively on both breasts. The contralateral reduction is typically done initially for symmetry. The reduction technique selected will depend on breast size, skin thickness, and surgeon preference/ comfort level. The skin-sparing mastectomy should be performed in the standard fashion and not through the reduction markings This will allow more versatility and durability of skin aps when it comes to shaping the breast. C: A total of 700 g was removed from the left breast. Zone 1 of her ipsilateral unipedicled transverse rectus abdominus myocutaneous ap was used for shaping of the breast mound. A skin island was included for symmetry with the opposite breast and for nipple reconstruction.

172

Section I Oncology and Oncoplastic Surgery

Figure 13.5. A: A 36-year-old obese woman with ductal carcinoma who underwent right mastectomy with immediate transverse rectus abdominus myocutaneous ap reconstruction. She desired large breasts for proportion with her body habitus. B: Periareolar skin takeout was performed on the right at the time of her mastectomy to improve overall breast shape. C: Contralateral mastopexy was performed for symmetry.

Implant Reconstruction
Expander/implant reconstruction will eliminate donor-site morbidity and is a reasonable option for bilateral reconstructions. Immediate implant reconstruction in large, ptotic breasts can be used in patients who are not candidates for autologous tissue reconstruction (30). In patients with very large breasts, one option is to perform a generous elliptical mastectomy and use dual-plane expander reconstruction with allograft and horizontal skin closure. This is reasonable in a bilateral reconstruction; however, shape is often poor and difcult to revise. Another option that provides better shape and symmetry is to use a Wise closure pattern. Preoperative Wise pattern or vertical breast reduction markings are drawn depending on skin quality, breast size, and surgeon comfort level with the various reduction procedures. The mastectomy is performed in the standard skin-sparing fashion if possible through a periareolar incision, not through the reduction markings. This will endure safer tension-free closure with more variability to adjust size

and shape in conjunction with the opposite side. Our preference is to use the lower mastectomy skin aps as a deepithelialized sling to cover the lower pole of the expander and sutured superiorly to the pectoralis muscle (Fig. 13.6). The skin aps are then closed using the Wise pattern, and if skin necrosis occurs at the T junction, this will heal secondarily without the risk of expander extrusion. Aggressive use of postoperative drains, is required given the risk of seroma formation.

PTOSIS
The reconstruction of ptotic breasts is becoming more common as the age and body habitus of women seeking breast reconstruction continue to increase. Volume loss is evident with stretch marks, descent of the nipple-areolar complex, and very thin skin. As the size of the breast or the degree of ptosis increases, so does the complexity of the reconstructive process. Skin quality, degree of ptosis, the patients wishes regarding

Chapter 13 Special Problems in the Treatment and Reconstruction of Breast Cancer

173

Figure 13.6. A: A 54-year-old obese woman (body mass index, 47) with macromastia and right breast cancer who underwent a skin-sparing mastectomy through an elliptical periareolar incision. A contralateral breast reduction was performed, removing 1,058 g. B, C: The right breast was reconstructed using a deepithelialized fasciocutaneous ap from the lower pole mastectomy skin, which was sutured to the pectoralis muscle, providing complete coverage of the expander with vascularized skin. D: She is shown 1 year following replacement of the tissue expander with a 550-cc smooth, round moderate prole gel implant.

shape and size of the opposite breast, and reconstructive options need to be addressed initially in consultation. The various reconstructive options have been discussed previously in this chapter and elsewhere for women with ptosis. I focus here on the different approaches to managing the skin envelope in women with ptosis, as this is important and often a difcult part of these reconstructions (Fig. 13.7). Reproducing a ptotic breast following skin-sparing mastectomy is possible with autologous tissue if the patient has minimal to moderate ptosis and wishes to maintain the degree of ptosis on the opposite side. However, a contralateral procedure with mastopexy, mastopexy/augmentation, or reduction will often improve overall breast shape as well as ease of reconstruction and the available reconstructive options. The type of mastopexy pattern, whether periareolar, vertical, or Wise pattern, will depend on breast size, degree of ptosis, skin quality, and amount of excess skin. Similar patterned skin removal on both sides will ensure the best symmetry; however, appropriate precautions should be taken on the mastectomy side to minimize wound healing issues as discussed earlier. Mastectomy skin aps will not tolerate the same closure

tensions seen in reduction mammaplasties. Ways to avoid this include performing skin takeout only after the regular skinsparing mastectomy has been performed or deepithelializing the skin aps inferiorly at the inframammary fold rather than excising the skin. This is more critical when implant coverage is required especially inferiorly, where skin ap necrosis will invariable lead to implant exposure. Numerous types of skin takeout patterns exist, which are essentially variants of Carlsons type V skin-sparing mastectomy pattern (Fig. 13.8). The safest method is probably to excise skin in a periareolar fashion and cinch the mastectomy skin aps around the autologous ap skin island or over an implant. This will often provide the necessary lift without the need for further skin envelope removal that might jeopardize the viability of the skin aps. The cinched skin will atten with time. This method is used in patients with minimal ptosis who undergo contralateral periareolar mastopexy for symmetry. Patients with moderate ptosis and excess thin skin require more skin to be removed for shape preservation. This is performed through the vertical or Wise skin takeout pattern. When a mastopexy augmentation is required on the

174

Section I Oncology and Oncoplastic Surgery

Figure 13.7. A reconstructive algorithm for thin and obese patients.

opposite side for the best shape, then a latissimus dorsi ap with implant and similar mastopexy pattern will ensure symmetry. It cannot be overstated that the mastectomy aps need to be treated with caution and respect, especially if skin takeout is going to be performed. If the aps appear thin and the viability is in question, use uorescein, debride questionable segments, and use more autologous skin island if possible. The closure patterns need to be adjusted for safety rather than trying to replicate the opposite side. In large breasts or those with signicant ptosis, another option is to delay the reconstruction to when the breast pocket and skin envelope can be determined at that time.

OTHER OPTIONS FOR WOMEN WITH MACROMASTIA


SSM and reconstruction in women with macromastia is challenging. Breast conservation therapy in the past was considered a relative contraindication in women with macromastia, given unfavorable cosmetic results and radiation dosing inhomogeneity (31). The use of reduction techniques in addition to partial mastectomy has been a good solution to some of these issues since it increases the indications for BCT in patients with macromastia and minimizes the risk of poor

Chapter 13 Special Problems in the Treatment and Reconstruction of Breast Cancer

175

No skin takeout

Peri-areolar skin takeout

Wise pattern skin takeout

Vertical pattern skin takeout

Figure 13.8. The skin takeout techniques will


vary, depending on breast size, shape, and skin quality. Deepithelialization as in approaches 5 and 6 will provide coverage and maximize the viability of skin aps.

De-epithelialized dermis

cosmetic results, in addition to the other benets discussed previously. We have recently shown that for women with macromastia requiring a contralateral reduction of greater than 300 g, the oncoplastic reduction (n 51) approach is preferred over SSM and reconstruction (n 30). The results demonstrated that in the oncoplastic group, the overall complication rate was less (22% vs. 50%), the breast complication rate was lower (22% vs. 47%), there were no donor-site issues, fewer operative procedures were required (2.4 vs. 5.9), and the overall patient satisfaction was slightly higher (32). Although the oncoplastic approach is considered the denitive surgery, if completion mastectomy is required, reconstruction is often easier since the breast is now smaller, the skin envelope has already been reduced, the contralateral

procedure has been performed, and no reconstructive option had been utilized.

CONCLUSION
Breast reconstruction in women with the extremes of body habitus and breast shapes can be challenging. Numerous options now exist to further improve cosmetic results while minimizing morbidity. These patients are often considered less-than-ideal candidates for breast reconstruction; however, attending to detail, strictly adhering to general principles, adapting the more traditional approaches, and offering appropriate preoperative counseling will maximize patient satisfaction in this population.

176

Section I Oncology and Oncoplastic Surgery

REFERENCES
EDITORIAL COMMENTS Patients expect a perfect outcome after reconstruction, even when their beginning body habitus is less than perfect. It is important that during the initial discussion about reconstruction the patient be given an honest, but not brutal, appraisal of the possible limitations her body habitus may have on her reconstruction options. There is a perception that plastic surgeons can work magic, and although that is often true, there is a starting palette, the patients body, that is the plastic surgeons resource. Many women turn the negative of a breast cancer diagnosis into a positivean opportunity to alter their breast size or contour. This chapter outlines the special problems presented to the plastic surgeon by the very heavy or thin woman or by the woman with ptotic breasts. These challenges are particularly difcult in the woman having a unilateral mastectomy who wants to attain symmetry without a contralateral procedure. We have all heard the phrase that you can never be too rich or too thin. Although the former may be true, in the breast reconstruction world, the latter is denitely not true. Although patients like to hear that they are thin, it is imperative that they understand the limits of autologous tissue transfer and the size of breast that can be reconstructed. This is especially true if bilateral reconstruction is desired with autologous tissue. When autologous tissue along with an expander is necessary to get the best cosmetic result, the patient must deal with the disadvantages of both and has fewer options if postmastectomy radiation is required. Patients who are obese invariably think that this is their golden opportunity to get a tummy tuck covered by insurance, and it seems that a TRAM ap is what they rst think of during a discussion about reconstruction. Obtaining a satisfactory cosmetic result for both the reconstructed breast and the donor site if autologous tissue is used is very difcult. In addition, fat necrosis is common, thus raising the concern of recurrence and often requiring diagnostic procedures to denitively rule out malignancy. In contrast, a mastectomy without reconstruction in a large-breasted woman results in areas of redundant skin at the posterior axillary line and/or at the edge of the sternum and imbalance if the mastectomy is unilateral. Clearly, the assessment for and execution of reconstruction in this challenging group of women is complex. Many women requiring a mastectomy for a new diagnosis of breast cancer focus their attention on the decision making about reconstruction rather than on their cancer. It is one decision over which they have control. Unfortunately, however, it is difcult to predict how their reconstruction will look and feel and how satised they will be with it. The reconstructive surgeon can help with patient satisfaction by counseling her about what to expect postoperatively, honoring her desired ideal breast size, and giving her some sense of what will happen to her reconstructed breast with weight loss or gain and with aging. S.C.W.
1. Kroll SS. Bilateral breast reconstruction in very thin patients with extended free TRAM aps. Br J Plast Surg 1998;51(7):535537. 2. Spiegel AJ, Khan FN. An intraoperative algorithm of use of the SIEA ap for breast reconstruction. Plast Reconstr Surg 2007;120(6):14501459. 3. Shaw WW. Superior gluteal free ap breast reconstruction. Clin Plast Surg 1998;25(2): 267274. 4. Fansa H, Schirmer S, Warnecke IC, et al. The transverse myocutaneous gracilis muscle ap: a fast and reliable method for breast reconstruction. Plast Reconstr Surg 2008;112(5): 13261333. 5. Spear SL, Spittler CJ. Breast reconstruction with implants and expanders. Plast Reconstr Surg 2001;107(1):177187. 6. Kronowitz SJ, Kuerer HM, Buchholz TA, et al. A management algorithm and practical oncoplastic surgical techniques for repairing partial mastectomy defects. Plast Reconstr Surg 2008;122(6):1632. 7. Losken A, Hamdi M. 2009. Partial Breast Reconstruction