Optimal Management of Primary
Breast Cancer
Atilla Soran, MD* and Victor G. Vogel, MD, MHS*
*University of Pittsburgh Cancer Institute/Magee-Womens Hospital, Pittsburgh, Pennsylvania
j Abstract: The diagnosis and treatment of breast cancer
have changed in response to not only new technologies but
also cultural and social aspects of the disease. While breast-
conserving surgery and adjuvant therapy are the preferred
treatments for many breast cancers, neoadjuvant therapy is
often used in advanced disease. In this review we examine the
treatment options that are influenced by pathologic and clini-
cal factors. Invasive breast cancer is a potentially curable dis-
ease if it is regarded and managed by a multidisciplinary ap-
proach from the outset. j
Key Words: breast cancer, management, primary, review
B reast cancer is one of the major cancer burdens
worldwide. The incidence has been increasing for
several decades and by the year 2000 breast cancer will
affect close to one million new women per year and
cause the death of over 400,000 women worldwide
(1,2). In this review we evaluate the therapeutic options
for the most common cause of cancer in women.
DUCTAL CARCINOMA IN SITU
While screening mammography has resulted in a sig-
nificant increase in the diagnosis of ductal carcinoma in
situ (DCIS), and information about size, nuclear grade,
and pathologic subtype aid in estimating the risk of re-
currence, the management of DCIS remains controver-
sial. The presence or absence of comedo necrosis, nu-
clear grade, size, extent of disease within the breast, and
Address correspondence and reprint requests to: Victor G. Vogel, MD,
Director, Comprehensive Breast Program, 802 Kaufman Building, 3471 Fifth
Ave., Pittsburgh, PA 15213-3221, U.S.A., or e-mail: vogelv@msx.upmc.edu
© 1999 Blackwell Science Inc., 1075-122X/99/$14.00/0
The Breast Journal, Volume 5, Number 2, 1999 81–93
the status of the resection margins are the most impor-
tant risk factors for local recurrence (3–11).
Mastectomy is a highly effective treatment for DCIS
(12), but it may be overtreatment in some women who
may not develop invasive carcinoma during their life-
times (3–5,11). Patients with mammograms showing
diffuse or multicentric, malignant-type microcalcifica-
tions and biopsy-proven DCIS are appropriate for mas-
tectomy (Fig. 1). Patients with tumors larger than 4 cm
in size, gross multicentric disease, positive margins, or
microinvasion despite reexcision also should be consid-
ered for mastectomy (3,8). Patients treated previously
with breast irradiation who then develop extensive areas
of recurrent DCIS are best treated with mastectomy.
Surgeons who prefer to do wide local excision alone
should keep in mind that the size of the tumor must be
less than 1 cm in diameter, it should be unicentric with-
out comedo necrosis and with clear margins, and have a
low nuclear grade (3,4,12–14). In addition, surgeons
should realize that although DCIS recurrences can be
successfully treated by reexcision alone, half the recur-
rences are invasive disease (4–6,9,12–16). Patients
treated previously with wide excision alone may be
treated with reexcision and radiation therapy (RT) at re-
currence if the lesion is both small and low grade (3).
The National Surgical Adjuvant Breast Project (NS-
ABP) B-17 trial of patients with DCIS showed that the
incidence of recurrent invasive carcinoma was decreased
from 10.5% to 2.9%, and incidence of recurrent nonin-
vasive disease decreased from 10.4% to 7.5% following
wide excision plus RT (12). Either high nuclear grade or
the presence of a close or positive margin was the most
important risk factors for development of local recur-
rence (5,6,10,17).
82 • soran and vogel

Figure 1. The treatment path-

ways of DCIS of the breast.
DCIS 5 ductal carcinoma in situ;
RT 5 radiation therapy; TM 5
total mastectomy; LND 5 lymph
node dissection; LNG 5 low nu-
clear grade; HNG 5 high nuclear
grade.

Patients with DCIS tumors larger than 1 cm in diame- is 0.0–22.9% (27–34) during 24 years following a diag-
ter who have either comedo necrosis or close margins nosis of LCIS.
can be treated with either mastectomy or wide excision Although 60–80% of LCIS is multicentric (35,36),
plus RT. Because recurrence rates are high in some series observation alone can be the preferred management ap-
following treatment by wide excision alone of DCIS that proach (37,38) (Fig. 2), because three of four women
is more than 1 cm in diameter, RT is required to lower with biopsy-proven LCIS will never develop invasive
breast recurrence rates (3,5,9,18–21).
Axillary lymph node metastases are found in less
than 1–2% of reported series of patients with DCIS (22–
25). Axillary dissection is not indicated as initial surgical
treatment for DCIS (4,18).
Very little information is available about the presence
of estrogen receptor (ER) expression and treatment suc-
cess with antiestrogens for DCIS. One study showed that
60% of lesions are positive for ER in DCIS (7), but the
data are limited. Long-term antiestrogen therapy may be
a treatment alternative for DCIS in the future, but there
are no data currently to recommend this approach.

LOBULAR CARCINOMA IN SITU

Lobular carcinoma in situ (LCIS) carries a significant
risk for development of subsequent invasive carcinoma.
LCIS is associated with an increased risk of approxi-
mately 7 to 10 times that of the general population
(25,26). The risk for development of breast cancer in the Figure 2. The treatment pathways of LCIS. LCIS 5 lobular carci-
biopsied breast is 4–29% and in the contralateral breast noma in situ; LND 5 lymph node dissection.

breast cancer (38). The policy of observation alone for
LCIS spares women from having mastectomy, and
mammographic or physical abnormalities that develop
in follow-up are likely to be detected at an early stage
when they are amenable to curative therapy (39). When
observation is elected, it must last for the patient’s life-
time because the risk of breast cancer is lifelong (39,40).
This abnormality is associated, however, with a risk of
invasive breast cancer that may be as high as 1% per
year of subsequent observation.
Unilateral simple mastectomy with contralateral bi-
opsy or wide surgical excision with or without RT are
inappropriate treatments for LCIS because LCIS carries
the risk of bilateral and multifocal breast cancer (41)
and is probably not the source of invasive lesions (38).
Because some patients insist that the risk of develop-
ing carcinoma must be totally excluded, surgeons may
elect bilateral mastectomy with or without reconstruc-
Optimal Management of Breast Cancer • 83
tion. Mastectomy is an alternative treatment for women
known to be at increased risk for breast cancer develop-
ment due to a positive family history or prior personal
history of breast cancer, or for those who are unwilling
to accept close follow-up. The subsequent mortality rate
from breast cancer is 0.9% when initial treatment of
LCIS is mastectomy (42).
LOCAL THERAPY OF EARLY STAGE BREAST
CANCER (STAGES I, IIa, IIb)
Recently there has been a trend toward patients pre-
senting with breast cancer at earlier stages (43), and sur-
vival of early stage breast cancer is excellent (44). Treat-
ment options have evolved from extensive surgical
approaches to conservative surgery in selected patients,
and conservative surgery and radiation represent an alter-
native that is equal to mastectomy (Figs. 3 and 4). For pa-
tients with disease confined to one quadrant, total mas-
Figure 3. Local therapy of early
stage unicentric breast cancer.
TM 5 total mastectomy; L 5
lumpectomy; I/II AD 5 level I/II
axillary lymph node dissection;
ALN 5 axillary lymph node; RT 5
radiation therapy.
84 • soran and vogel
Figure 4. Local therapy of early stage multicentric breast cancer.
TM 5 total mastectomy; I/II AD 5 level I/II axillary lymph node
dissection; RT 5 radiation therapy; CT 5 chemotherapy; ALN 5
axillary lymph node.
tectomy with level I/II axillary lymph node dissection is
equivalent to lumpectomy with level I/II axillary lymph
node dissection followed by radiation therapy when rates
of recurrence and survival are compared (45–50). Patient
selection may have the greatest impact on local-regional
recurrence rates. Although extension of invasive tumor to
the resection margin is not an independent risk factor for
recurrence, recurrence rates are lower when margins are
negative rather than positive or indeterminate (48,51,52).
It is generally accepted that an adequate wide local exci-
sion of breast cancer means a clearance of 20 mm, micro-
scopically proven by frozen section at surgery and con-
firmed by subsequent paraffin section (52).
Studies have demonstrated that patients with tumors
up to 5 cm may be treated conservatively with equivalent
outcomes to more aggressive therapies. There is a relation
between tumor size and local recurrence, and the risk of
recurrence is very high if the primary tumor is larger than
5 cm (53–59). In some series, an extensive intraductal
component on histologic examination was found to be a
significant factor for recurrence (60,61), but this finding
has not been confirmed. In addition, some authors em-
phasize that lymphatic vessel invasion or blood vessel in-
vasion modestly increases the risk of local failure follow-
ing conservative surgery and RT (62–66).
There are few contraindications to breast preserva-
tion. A preexisting history of collagen vascular disease,
pregnancy, diffuse malignant microcalcifications, multi-
centricity, or prior breast RT are absolute contraindica-
tions for RT (43,48,50), and a subareolar location, a
small breast with a large tumor, and focally positive
margins are relative contraindications. Age is not a con-
traindication for breast-conserving surgery (67–70).
When total mastectomy is the chosen initial treat-
ment for early stage of breast cancer, adjuvant chest
wall and nodal RT is indicated for patients with a posi-
tive resection margin, a tumor 5 cm or larger in greatest
diameter, for patients with four or more positive axil-
lary lymph nodes, or for patients with pathologic in-
volvement of the pectoralis fascia (71–73).
For patients undergoing lumpectomy, diagnostic
three-view mammography should be performed after
surgery (50,70,74). If there is evidence of gross residual
disease, reexcision should be performed (75,76). Pa-
tients with persistently positive pathologic margins after
reexcision should have total mastectomy (49,50,76). Pa-
tients with pathologic involvement of the chest wall or
involvement of four or more positive nodes after total
mastectomy are candidates for chest and nodal irradia-
tion. Patients who have negative diagnostic mammogra-
phy following lumpectomy or pathologically negative
margins following reexcision should receive breast irra-
diation following lumpectomy (75). Nodal irradiation
may be indicated for patients with four or more in-
volved axillary nodes (77).
LOCAL THERAPY OF LOCALLY ADVANCED
BREAST CANCER (STAGE IIIa,
NONINFLAMMATORY STAGE IIIb)
Despite the increase in early diagnosis of breast cancer
through the introduction of screening techniques, locally
advanced breast cancer remains a significant problem. Un-
fortunately, 10–35% of women with breast cancer still
have locally advanced disease at initial diagnosis (78,79).
Management of stage IIIa and noninflammatory
stage IIIb disease is divided into patients who are judged
to be inoperable and patients who are operable. Inoper-
able patients receive preoperative (neoadjuvant) chemo-
therapy because most patients achieve a response to
chemotherapy, resulting in downstaging of the tumor
(79–81) (Fig. 5). It may be desirable to include a skin tat-
too or other marker to indicate the pretherapy extent of
the measurable tumor. The number of preoperative che-

motherapy cycles is a matter of clinical judgment, but
usually three or four cycles are given. After chemotherapy
the patient is assessed to be either operable or inoperable.
Operable patients who are candidates for lumpectomy
may receive this procedure with treatment guidelines as
defined for local therapy of early stage breast cancer
(82,83) (Fig. 6). Patients who are not candidates for
lumpectomy should be treated with modified radical
mastectomy and receive postoperative chest wall and
nodal irradiation therapy (84). Patients who are judged
to be inoperable following neoadjuvant chemotherapy
should receive preoperative radiotherapy (85). Patients
who are judged to be responders to RT may then be con-
sidered for additional local or systemic therapy. Nonre-
sponders should complete radiotherapy to a high dose.
For patients with operable locally advanced breast can-
cer, administration of neoadjuvant chemotherapy is the
Optimal Management of Breast Cancer • 85
Figure 5. Local therapy for locally
advanced (stage IIIa/IIIb nonin-
flammatory) inoperable breast
cancer. RT 5 radiation therapy;
CT 5 chemotherapy; MRM 5
modified radical mastectomy.
preferred treatment choice (85–87). Patients who do not
respond or who respond poorly to neoadjuvant chemo-
therapy should be treated with a modified radical mastec-
tomy and level I/II axillary lymph node dissection (88).
These patients should then receive postoperative chest
wall and nodal radiation therapy. Significant improve-
ment has been reported in local-regional control and over-
all survival with the addition of radiation (89). Patients
with complete or partial response assessed both clinically
and mammographically who are amenable to lumpec-
tomy may receive this therapy as described above (88).
INFLAMMATORY (STAGE IIIb) BREAST CANCER
Inflammatory breast cancer (IBC) is a rare and ag-
gressive subtype of invasive breast cancer traditionally
associated with an extremely poor prognosis. Recently,
multimodality treatment regimens have resulted in a sig-
86 • soran and vogel
nificant improvement in local disease control and pro-
longed survival (90–98). Patients with classical physical
signs of inflammatory breast cancer are candidates for
neoadjuvant chemotherapy (Fig. 7). It has been empha-
sized that the majority of patients achieved a more than
50% decrease in their primary tumor mass, as assessed
by physical examination, and between 10% and 20% of
patients achieved a clinical complete remission (80). Pa-
tients with a complete pathologic response may be can-
didates for breast preservation (99,100). Inflammatory
tumors are often diffuse and poorly defined, and conser-
vative surgery and radiation are not practical options. In
addition, breast conservation for IBC requires higher
doses of radiation because residual tumor cannot be ad-
equately resected with less than a total mastectomy
(101). The local therapy of choice is modified radical
mastectomy with level I/II axillary lymph node dissec-
tion as well as postoperative chemotherapy and radia-
tion therapy (102–104). Patients with a partial response
Figure 6. Local therapy for lo-
cally advanced operable breast
cancer. MRM 5 modified radical
mastectomy; ALND 5 level I/II
axillary lymph node dissection;
RT 5 radiation therapy; CT 5 che-
motherapy; PR 5 partial response
(.50% decrease in measurable
tumor diameter); CR 5 complete
response—clinically and mam-
mographically; Poor response:
,50% decrease in measurable
tumor diameter.
who are judged inoperable or patients not responding to
preoperative chemotherapy should be treated with 45
GY radiation therapy (94,101). Patients who are opera-
ble following radiation therapy should undergo modi-
fied radical mastectomy with level I/II axillary lymph
node dissection and postoperative chemotherapy. Addi-
tional radiation therapy may be indicated for patients.
Patients remaining inoperable after initial radiation
therapy should receive additional chemotherapy fol-
lowed by 70 GY radiation to the breast and 50 GY to
the nodal region (105). Additional chemotherapy may
then be indicated depending on response.
ADJUVANT THERAPY
The aim of adjuvant systemic treatment is to avoid
relapses and to reduce mortality from breast cancer. Al-
though tumor involvement of the axillary lymph nodes
is the strongest predictor of recurrence after surgery,
rates of recurrence even in those women with no nodal

involvement can be as high as 30% at 5 years and 40%
at 10 years after surgery. Mortality rates can reach 22%
at 5 years and 35% at 10 years (106,107).
Optimal adjuvant therapy regimens including agents,
dosage, schedule, and total number of treatment cycles
remain to be completely defined. In general, patients may
be divided into various prognostic categories that are de-
pendent upon tumor size, nodal status, and hormone re-
ceptor status. Patients with negative axillary nodes and
tumors less than 1 cm may be appropriate candidates for
no additional therapy (108). Among node-negative pa-
tients, the World Consensus Conference meeting in St.
Galen, Switzerland, in 1995 (105) recommended stratifi-
cation into minimal/low-risk, good-risk, and high-risk
patients. Minimal risk means a primary tumor size less
than 1 cm, estrogen receptor (ER) positive, nuclear grade
1, and age greater than 35 years; good risk: tumor size 1–
2 cm, ER positive, nuclear grade 1–2; high risk (at least
one of the listed factors is present): tumor size greater
Optimal Management of Breast Cancer • 87
Figure 7. The treatment path-
way of inflammatory (stage IIIb)
breast cancer. MRM 5 modified
radical mastectomy; ALND 5
level I/II axillary lymph node dis-
section; RT 5 radiation therapy;
PR 5 partial response (.50%
decrease in measurable tumor
diameter); CR 5 complete re-
sponse—clinically and mammo-
graphically; Complete RT 5 70
GY to breast, 50 GY to regions;
Boost RT 5 postoperative RT
(10–20 GY to tumor bed).
than 2 cm, ER negative, nuclear grade 2–3. Therapy for
these patients is further described in Figure 8. The treat-
ment of choice depends upon risk group, menopausal sta-
tus, and ER status. Premenopausal patients in the good-
risk category who are ER positive may be treated with
tamoxifen as the treatment of choice (109). However,
evaluation of ovarian ablation, chemotherapy, and GnRH
analogs may be appropriate in clinical trials. Good-risk,
postmenopausal, ER-positive patients or the elderly should
be treated with tamoxifen (109).
The treatment of choice for high-risk, node-negative
patients is chemotherapy if the patient is premenopausal
(109). ER-positive, postmenopausal patients may be
treated with tamoxifen alone, as may elderly patients
(107,110,111). ER-negative postmenopausal patients
should receive chemotherapy. The addition of tamox-
ifen to chemotherapy regimens or the addition of che-
motherapy to adjuvant tamoxifen therapy is being eval-
uated in ongoing clinical trials.
88 • soran and vogel
Patients with four or more positive axillary lymph
nodes who are 50 years of age or older and who are ER
positive are candidates for 5 years of tamoxifen therapy
(112) (Fig. 9). Chemotherapy should be added to the
treatment of patients with four or more positive lymph
nodes who are younger than 50 or who are older than
50 with negative hormone receptors (113). In patients of
any age who receive adjuvant chemotherapy, the addi-
tion of tamoxifen therapy for 5 years is optional, but
may add additional benefit (114).
For patients with 10 or more positive lymph nodes,
participation in high-dose chemotherapy clinical trials
with stem cell support may be offered, if available (115).
Figure 8. Adjuvant treatment
for patients with node-nega-
tive breast cancer. M 5 minimal/
low risk; G 5 good risk; H 5
high risk; ER 5 estrogen recep-
tor status.
The use of high-dose therapy outside a clinical trial
should be avoided.
CONCLUSION
Patients should be evaluated closely before surgery,
and appropriate treatment options should be offered ac-
cording to breast cancer stage. Surgeons should keep in
mind that although removal of the tumor is the main lo-
cal treatment of breast cancer, improved disease-free in-
tervals can be obtained if multimodal therapy is used.
Conservative treatment is gaining popularity among both
physicians and patients. Breast cancer therapy should be
done by a team that is familiar with the disease, and local

management guidelines should be developed in collabo-
ration with surgeons, radiologists, pathologists, medical
oncologists, and radiation oncologists. With this collabo-
ration each institution can develop management path-
ways that are appropriate to their local resources and
their most commonly seen patient presentations.
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