The Breast

Chapter 17. Schwartz 10th edition 2015

Roberto B. Acuña, MD, FPCS, FPSGS, FPALES, FPBCS
FEU-NRMF Department of Surgery
Topics
• Embryology and functional anatomy
• Congenital anomalies

• Physiology

• Common benign disorders & infectious diseases

• Breast cancer
Congenital breast lesions

EMBRYOLOGY AND
FUNCTIONAL ANATOMY
Polymastia
Accessory Breast
The “Milk Line”
Polymastia
Excision → MRM
Axillary Nerves (4) + 4 muscles
• Intercostobrachial nerve
• Sensory to the axilla and medial arm

• Lateral pectoral nerve

• Pectoralis major and minor m.

• Thoraco-dorsal nerve
• Latissimus dorsi m.

• Long thoracic nerve

• Serratus anterior m.
Venous & Lymphatic Drainage
Lymphatic Drainage
Physiology
Sweat Gland Mammary Gland
Lobular and Ductal Distribution
Ductography

TERMINAL DUCTULE OR
ACINUS
Fibroadenoma
Fibrocystic Change vs. Breast Cyst
Galactocele
Gynecomastia
Tuberculosis of the breast

BENIGN BREAST MASSES

Fibroadenoma
Breast Cyst
Breast Cyst

CYST WITH SOLID COMPONENT EXCISED

Fibrocystic Change

Magnetic Resonance Imaging

Galactocele
Gynecomastia
Adolescent Gynecomastia Senescent Gynecomastia
Gynecomastia
Prepubertal
Breast Tuberculosis
A. Risk factors
B. Epidemiology
C. Natural History
D. In situ versus Invasive Breast Cancer
E. Diagnosis
F. Staging and Biomarkers
G. Surgical Techniques in Breast Cancer Surgery
H. Breast Cancer Treatment by Stage
I. Special Clinical Situations

BREAST CANCER
A. Risk Factors
• Risk
• Chance for an event to occur
• Absolute Risk (AR)
• An individual’s likelihood of developing breast cancer

Source: Breastcancer.org 2014

• 12% chance over an 80 year lifespan
• 20 y/o 0.06%
• 30 y/o 0.44%
• 40 y/o 1.45%
• 50 y/o 2.31%
• 60 y/o 3.49%
• 70 y/o 3.84%

• Relative Risk (RR)

• Compares risk of one group with exposure vs. general population
• Example: Alcoholics = 1.5x RR of breast cancer = 18%
Risk Factors
Hormonal Non-hormonal
• Exposure to estrogen • Radiation exposure
• Increased risk • 75x ↑
• Early menarche • Alcohol intake
• Nulliparity • 1.5x ↑
• Late menopause • High fat diet
• Decreased risk
• 1st degree relative with
• Moderate exercise
breast cancer
• Prolonged lactation
• 2-3x ↑
• Obesity • BRCA1 & BRCA2 mutation
• 85% lifetime risk (AR)
B. Epidemiology
• Most common site-specific cancer in women

• Most common cause of mortality in women 20-59 years old

• Environmental pollution, radiation

• Pampanga
• Highest breast cancer density in the Philippines
Incidence
Sporadic breast cancer 65 – 75 % 70

Familial breast cancer 20 - 30 % 25

Hereditary breast cancer 5 – 10 % 5
BRCA 1 45 %
BRCA 2 35 %
p53 (Li-Fraumeni syndrome) 1%
STK11/LKB1 (Peutz-Jeghers syndrome) <1%
PTEN (Cowden disease) <1%
MSH2/MLH1 (Muir-Torre syndrome) <1%

ATM (Ataxia-telangiectasia) <1%

Unknown 20 %
C. Natural History of Breast Cancer
• Untreated breast cancer
• Median survival of 2.7 years
• 18% 5YSR; 3.6% 10YSR
• Often with ulceration
Natural History of Breast Cancer
• Cooper’s ligaments
Fibrosis → Nipple Retraction
Peau d’orange
Ulceration
Satellite Nodules
D. In-situ versus Invasive Ca
• Benign

• Atypia

• In-situ

• Invasive
Table 17.8
Salient Characteristics of LCIS vs. DCIS
LCIS DCIS
Age (years) 44-47 (seen in women only) 54-58 (seen in both sexes)

Incidence 2-5% 5-10%

Clinical signs None Mass, pain, discharge
Mammogram signs None (only in neighboring tissues) Microcalcifications
Premenopausal 2/3 1/3
Incidence, invasive ca 5% 2-46%
Multicentricity 60-90% 40-80%
Bilaterality 50-70% 10-20%
Axillary mets 1% 1-2%
Subsequent carcinoma
Incidence 25-35% 25-70%
Laterality Bilateral Ipsilateral
Interval to diagnosis 15-20y 5-10y
Histologic type Ductal Ductal
Invasive Breast Cancer Types
• Invasive Ductal Carcinoma 80%
• Invasive Lobular Carcinoma 10%
• Medullary Carcinoma 4%
• Mucinous Carcinoma 2%
• Papillary Carcinoma 2%
• Tubular Carcinoma 2%
• Paget’s disease of the nipple
• Rare cancers
• Adenoid cystic carcinoma
• Squamous carcinoma
• Apocrine carcinoma
Invasive Ductal Carcinoma
• 80%

• Stellate

• Microcalcifications
Invasive Breast Cancer
Ductal Lobular Medullary Mucinous Papillary Tubular
Age in 40-60 Elderly Perimenop
years ausal
Gross Stellate, Soft, h’gic Bulky Small,
calcificatio Bulky <3cm
n Deep
LN (+) 60% 33% Low 10%
ER (+) 75% >90% <10% >90% 87% 94%
Bilateral Low High 20%
Long term 100%
survival
Microscopic (page522)

Invasive Ductal Cancer Invasive Lobular Cancer

Fibrosis “Indian file”

1. Clinical
2. Imaging
3. Biopsy

E. DIAGNOSIS OF BREAST CANCER

E1. Chief Complaints
• Mass in the breast and/or axilla
• Breast pain
• Nipple changes
• Erythema, scaling
• Retraction
• Nipple discharge
• Skin changes
• Erythema
• Ulceration
• Satellite nodules
Breast and/or Axillary Mass
Asymmetry, Painless Mass
Nipple Changes

Hidradenitis suppurativa INCISION BIOPSY

Mycosis
Paget’s Disease Paget’s Disease (IN SITU)
Nipple Retraction
Nipple Discharge
Ulceration, Erythema
Skin Changes
Peau d’ Orange Satellite Nodules
E2a. Mammography
E2b. Ductography
E2c. Ultrasound
E2d. Magnetic Resonance Imaging (MRI)

E2. BREAST IMAGING

E2a. Mammography
Cranio-Caudal (CC) view Medio-Lateral Oblique (MLO)
Indications for Mammography
• Screening Mammography
• Detect unexpected cancer in asymptomatic women

• Diagnostic Mammography
• Evaluate abnormal findings such as breast mass or nipple
discharge
CC view
Premenopausal Postmenopausal
MLO view
Premenopausal Postmenopausal
Benign Vs. Malignant
Mass Calcification

WELL CIRCUMSCRIBED MACRO, SCATTERED

1 SPICULATED/STELLATE 2 LINEAR/BRANCHING (clustered)

 (PAGE525)

ASYMMETRICAL THICKENING

3
Advantages of Mammography
• More sensitive than clinical examination
• 90% true positive rate
• In women 50-59 yo
• 25% decrease mortality
• NCCN 2014 guidelines for normal risk women
• ≥ 20yo CBE every 3 years
• ≥ 40yo annual mammogram
• Decreased accuracy due to dense breast
• Breast Tomosynthesis (3D) is better in <50 yo
E2b. Ductography for bloody nipple discharge

INTRADUCTAL PAPILLOMA
Intraductal Papilloma
E2c. Ultrasound
• To resolve equivocal mammographic features
• To define cystic masses
• To define the echogenic qualities of solid lesions
• To guide needle biopsy
• To image axillary nodes in patients with breast cancer
• Cortical thickening
• Loss of fatty hilum
• Change to a more circular shape
• Size more than 10mm
• Hypoechoic internal features
Ultrasound Benign
Simple Cyst Complex Cyst

BENIGN
Ultrasound Benign
Fibroadenoma Intraductal Papilloma
Ultrasound Malignant
Irregular with microcalcification Spiculated mass
Magnetic Resonance Imaging
• Used only if ultrasound and mammogram are not conclusive
• Possible applications
• Assess axillary mets without breast primary
• Assess result of neoadjuvant treatment
• Evaluate breast for tumor recurrence in BCS
Imaging Summary
< 40 years old, low risk > 40 years old
• CBE every 3 years • Mammogram
• Ultrasound • Ultrasound
• Breast Tomosynthesis • MRI?
Non palpable vs. palpable lesions

E3. BREAST BIOPSY

Breast biopsy not palpable page529

• With a mass
• Ultrasound-guided needle localization biopsy

• Without mass (architectural distortion or calcification only)

• Mammogram-guided needle localization biopsy
• Stereotactic
 EXCISION BIOPSY

SPECIMEN MAMMOGRAM
Breast biopsy palpable mass
Fine Needle Aspiration Cytology Core needle biopsy

CELLS TISSUE
Breast biopsy palpable mass
Excision Biopsy if ≤ 3cm Incision Biopsy if > 3cm
A. Risk factors
B. Epidemiology
C. Natural History
D. In situ versus Invasive Breast Cancer
E. Diagnosis
F. Staging and Biomarkers
G. Breast Cancer Treatment by Stage
H. Surgical Techniques in Breast Cancer Surgery
I. Special Clinical Situations

BREAST CANCER
T = Tumor size

N = Nodal Status

M = Metastasis (Distant)

BREAST CANCER STAGING PAGES531-534

T = Tumor Size
Negative correlation
Disease-free survival
Overall survival

Positive correlation
Axillary node mets
N =Axillary Nodal Status
• Negative correlation
• Disease-free survival
• Overall survival

• On recurrence
• Node negative = 30% recur
• Node positive = 75% recur
M = Distant Metastases page518

• Vertebral column
• Via Batson’s plexus
• Lung
• Via axillary vein and intercostal veins
• Pleura
• Soft tissues
• Liver
• Brain
• In triple receptor negative tumors

• 95% of breast cancer deaths

• Starts at 27th doubling (0.5cm)
Staging
N0 N1 N2 N3
Stage 0 T is
Stage I T1 *
Stage II A T2 T 0, T 1
II B T3 T2
Stage III A T3 T 0, T 1, T 2, T3
III B T4 T4 T4
III C Any T
Stage IV Any T, Any N, M1
Adapted from AJCC Cancer Staging Manual 7th Edition 2010
Biomarkers
• Risk factor biomarkers
• Familial clustering
• Inherited germline abnormalities BRCA 1, BRCA 2
• Proliferative breast disease with atypia
• Mammographic densities

• Exposure markers
• DNA adducts

• Surrogate endpoint markers

• Histologic changes
• Indices of proliferation
• Genetic alteration leading to cancer
Biomarkers
• Prognostic and Predictive Biomarkers
• Steroid hormone receptor pathway (ER / PR assay)
• Growth factors and growth factor
• Human epidermal growth factor receptor 2 (Her2/neu)
• Epidermal growth factor receptor (EGFR)
• Transforming growth factor
• Platelet-derived growth factor
• Insulin-like growth factor
• Indices of proliferation
• Proliferating cell nuclear antigen (PCNA), Ki-67
• Indices of angiogenesis
• Vascular endothelial growth factor (VEGF); angiogenesis index
• Mammalian target of rapamycin (mTOR)
• Tumor suppressor genes – p53
• The cell cycle, cyclins, cyclin-dependent kinases
• The proteosome
• COX-2 enzyme
• Peroxisome proliferator-activated receptors (PPARs)
• Indices of apoptosis and apoptosis moderators such as bcl-2 & bax:bcl-2 ratio
Coexpression of Biomarkers
• ER
• PR
• Her2/neu

• POSITIVE ER and PR > 50% response to HT

• POSITIVE ER or PR 33% response
• NEGATIVE ER and PR < 10% response

• Her-2/neu
• Positive Poor prognosis; Good response to Trastuzumab
• Negative Better prognosis; No response to Trastuzumab
Trastuzumab (Herceptin)
• Trastuzumab alone
• Now approved as 1st line for metastatic breast cancer

• Trastuzumab + Chemotherapy
• Now approved as 1st line for early breast cancer
• 50% reduction of Recurrence Risk
• 33% reduction in Mortality
Oncotype DX
• 21-gene assay
• Determines prognosis and treatment
• RECURRENCE SCORE

• If node negative and ER positive

• HIGH RECURRENCE SCORES → Chemotherapy
• LOW RECURRENCE SCORES → Hormonal (Endocrine Therapy)
• INTERMEDIATE SCORE
• Research is ongoing
MammaPrint test
• 70-gene assay
• In node negative and 1-3 node positive breast cancer

• Phase III trial

• MOLECULAR MARKERS VS. BIOMARKERS

A. Risk factors
B. Epidemiology
C. Natural History
D. In situ versus Invasive Breast Cancer
E. Diagnosis
F. Staging and Biomarkers
G. Surgical Techniques in Breast Cancer Surgery
H. Breast Cancer Treatment by Stage
I. Special Clinical Situations

BREAST CANCER
Surgical Techniques for Cancer
• Radical Mastectomy
• The whole breast
• Axillary lymph nodes levels I, II, III
• Pectoralis major and minor muscles
• Modified Radical Mastectomy
• The whole breast and lymph nodes levels I, II, III only
• Total Mastectomy
• The whole breast only
• Breast Conservation Surgery (BCS)
• Removes the involved part of the breast only + 1cm normal margin
• Lumpectomy, segmental/partial mastectomy,
wide excision, tylectomy
• Extended Radical Mastectomy
• Plus ribs, lungs
Lumpectomy
Lumpectomy
QuART
Modified Radical Mastectomy
Modified Radical Mastectomy
Radical Mastectomy
Skin-sparing Mastectomy
A. Risk factors
B. Epidemiology
C. Natural History
D. In situ versus Invasive Breast Cancer
E. Diagnosis
F. Staging and Biomarkers
G. Surgical Techniques in Breast Cancer Surgery
H. Breast Cancer Treatment by Stage
I. Special Clinical Situations

BREAST CANCER
Requirements Prior to Treatment
• Biopsy result

• Clinical Stage
• T
• N
• M
• METASTATIC SURVEY

• Biomarker assay ( Triple Receptor Assay )

• General Health Status of the Individual

Table 17-3
Diagnostic Studies for Breast Cancer (Adapted) page536

BREAST CANCER STAGE

0 I II III IV
Hx and PE ● ● ● ● ●
CBC ● ● ●
Liver Fx Tests, including ALP ● ● ●
ER / PR (Hormone Receptors) ● ● ● ● ●
HER-2/neu ● ● ● ●
Bone scan S S S ● ●
CXR ● ● ●
Abdominal CT scan or US S S S ● ●
Mammogram and/or US ● ● ● ● ●

S – required if symptomatic
Table 17-3
Diagnostic Studies for Breast Cancer (Adapted) page536

BREAST CANCER STAGE

0 I II III IV
Hx and PE ● ● ● ● ●
CBC M M ● ● ●
Liver Fx Tests, including ALP M M ● ● ●
ER / PR (Hormone Receptors) ● ● ● ● ●
HER-2/neu Ᵽ Ᵽ Ᵽ Ᵽ
Bone scan S S S ● ●
CXR M M ● ● ●
Abdominal CT scan or US S S S ● ●
Mammogram and/or US ● ● ● ● ●

M – MY PRACTICE
Ᵽ - IF THEY CAN AFFORD TRASTUZUMAB
Treatment of Stage 0 (In-situ)
LCIS
• Marker for increased risk,
rather than precursor of
invasive cancer
• 30% develop invasive cancer
• Treatment Options
• Observation after excision
• Chemoprevention
• Tamoxifen
• Bilateral total mastectomy
• Usually diffuse & bilateral
DCIS
• Precursor of invasive cancer
• Treatment Options
• Lumpectomy + RT
• for less extensive disease
• Mastectomy
• for extensive disease
• Sentinel Node Dissection
• Adjuvant Tamoxifen
• ER positive
• NO SINGLE CORRECT
TREATMENT (Page 538)
Early Invasive Breast Cancer
(Stage I, IIA, IIB)

• Lumpectomy +RT*
• Same DFS, DDFS, OS as Mastectomy
• For localized disease and no BRCA mutation
• Mastectomy
• BCS + ALND/ SLND + RT (QuART)
• Not for multicentric, lobular, BRCA mutation (+), prior RT
• MRM
• Reconstruction?
• Skin Sparing
• Nipple Areola-Sparing
• Chemotherapy
Sentinel Node for < 2 (+) LN only
Sentinel Node
Lymphedema in elderly & obese patients
GeneSearch Breast LN Assay
• Searches for mammoglobin and cytokeratin 19
• Same use as frozen section
• To see if lymph nodes harbor metastatic disease
Early Invasive Breast Cancer
(Stage I, IIA, IIB)

• Surgery (Lumpectomy +RT vs. BCS/MRM)

• Adjuvant Treatment
• Chemotherapy with Paclitaxel+AC or Docetaxel+Carboplatin if ER/PR (-)
• Node positive (T0,T1 N1)
• > 1cm tumor (T1b N0; T2 N0)
• < 0.5cm tumor & node (-) but with adverse prognostic factors
• ER/PR (-)
• Her-2/neu (+)
• Lymphovascular invasion
• High nuclear grade
• High histologic grade
• Hormonal Therapy if without adverse prognostic factors
• Tamoxifen vs. Aromatase Inhibitor (AI)
Hormonal Therapy
Tamoxifen Aromatase Inhibitor (AI)
• Competitive Inhibitor to estrogen • Inhibits the last step in estrogen
production

E T

ER

PR
Hormonal Therapy
Tamoxifen Aromatase Inhibitor (AI)
• Competitive Inhibitor to estrogen • Inhibits the last step in estrogen
production

E T

ER
Early Invasive Breast Cancer
(Stage I, IIA, IIB)

N0 N1 TREATMENT
Surgery CT / HT RT
Stage I A T1 ● -/+
(T1a, T1b)
IB T 0/T 1, ● ●
N 1mi
Stage II A T2 T 0, T 1 ● ●
II B T3 T2 ● ●
Advanced Local-Regional Breast Cancer
(Stage III A, III B)

N0 N1 N2 Treatment
Surgery CT / HT RT

Stage III A T3 T 0, T 1, ● ● ●
T 2, T3
III B T 4 T4 T4 ● ● ●
Radiotherapy

After MRM After BCS

Advanced Local-Regional Breast Cancer
(Stage III A, III B)

T4d – Inflammatory Carcinoma Matted Axillary Nodes, Skin (+)

Advanced Local-Regional Breast Cancer
(Stage III A, III B)

If ER/PR (-)
Neoadjuvant Chemotherapy
Neoadjuvant CTx
Neoadjuvant Chemotherapy
Primary Endocrine Therapy
• If ER/PR (+)

• Also given pre-op

• Followed by sequential HTx

• For locally advanced

Distant Metastases (Stage IV)
• Palliative only especially QoL
• HT + RT + bisphosphonates for bone mets
Distant Metastases (Stage IV)
• CTx for visceral mets

After 2 sessions After 6 sessions

Resectable Liver Mets + CT
Mets to Orbit
Stage IV Breast Cancer
• Multidisciplinary Approach
• Resective procedures improve survival
• Including Total Mastectomy
• Local therapy may be required
• Malignant pleural effusion
• Impending pathologic fracture
• Spinal cord compression
• Painful bone and soft tissue mets
• Brain mets
• Pericardial effusion
• Ureteral and biliary obstruction
Local-Regional Recurrence
Local-Regional Recurrence
After BCS After MRM

CT or HT CT or HT
Prognosis of Breast Cancer
Stage 5-YEAR SURVIVAL RATE
(SEER data 2003-2009)

Stage I 98.6%

Stage II 84.4%

Stage III > 50%

Stage IV 24%
Phyllodes Tumor
Male Breast Cancer
Inflammatory Cancer
Rare Cancers
Reconstruction after MRM

SPECIAL SITUATIONS
1. Phyllodes Tumor page555

• Confusion with benign PT, malignant PT and fibroadenoma

• Differentiated by molecular biology
• Fibroadenoma are monoclonal or polyclonal
• Phyllodes are always monoclonal
• Gross cut section
• Leaf-like pattern
• Subtypes
• Benign < 5 mitoses/HPF
• Borderline 5-10 mitoses/HPF
• Malignant >10 mitoses/HPF
• Treatment
• Wide excision to BCS to Total Mastectomy*
Phyllodes Tumor Benign Type
Phyllodes Tumor Borderline Type
2. Male Breast Cancer
• Asymmetrical
• Vs. gynecomastia

• 80% invasive ductal

cancer

• Mostly ER/PR (+)

• MRM + HT
3. Inflammatory Cancer
• ≥ one-third of the
breast diameter
4. Rare Cancers
• TYPES
• Squamous cell cancer
• No skin invasion
• Adenoid cystic carcinoma
• Same histology as the salivary gland
• Apocrine carcinoma
• Sarcoma
• Same treatment as Phyllodes Tumors
5. Reconstruction After MRM
Reconstruction After MRM
Topics
• Embryology and functional anatomy
• Congenital anomalies

• Physiology

• Common benign disorders infectious diseases

• Breast cancer
A. Risk factors
B. Epidemiology
C. Natural History
D. In situ versus Invasive Breast Cancer
E. Diagnosis
F. Staging and Biomarkers
G. Breast Cancer Treatment by Stage
H. Surgical Techniques in Breast Cancer Surgery
I. Special Clinical Situations

BREAST CANCER