June 1, 2010 ◆ Volume 81, Number 11?
American Family Physician 1339
Treatment of Breast Cancer
University of Virginia School of Medicine, Charlottesville, Virginia
ments? continue? to? evolve,? and? although?
family? physicians? do? not? generally? make?
primary? decisions? about? these? therapies,?
Breast? cancer? prognosis? and? treatment?
histologic? grade,? hormone? receptor? status,?
pausal? status? and? age? are? also? important?
reast? cancer? is? the? second? most?
factors.? Table 2? outlines? typical? treatment?
Stage 0: In Situ
Lobular? carcinoma? in? situ? is? an? inciden-
not? progress? to,? but? increases? the? risk? of,?
breast? by? approximately? 7? percent? over? ?
not? indicated,? but? affected? women? should?
The? National? Comprehensive? Cancer? Net-
work? recommends? annual? mammography?
and? clinical? breast? examination? every? six?
Understanding breast cancer treatment options can help family physicians care for their patients during and after
cancer treatment. This article reviews typical treatments based on stage, histology, and biomarkers. Lobular carci-
noma in situ does not require treatment. Ductal carcinoma in situ can progress to invasive cancer and is treated with
breast-conserving surgery and radiation therapy without further lymph node exploration or systemic therapy. Stages
I and II breast cancers are usually treated with breast-conserving surgery and radiation therapy. Radiation therapy
following breast-conserving surgery decreases mortality and recurrence. Sentinel lymph node biopsy is considered for
most breast cancers with clinically negative axillary lymph nodes, and it does not have the adverse effects of arm swell-
ing and pain that are associated with axillary lymph node dissection. Choice of adjuvant systemic therapy depends
on lymph node involvement, hormone receptor status, ERBB2 (formerly HER2 or HER2/neu) overexpression, and
patient age and menopausal status. In general, node-positive breast
cancer is treated systemically with chemotherapy, endocrine therapy
(for hormone receptor–positive cancer), and trastuzumab (for can-
cer overexpressing ERBB2). Anthracycline- and taxane-containing
chemotherapeutic regimens are active against breast cancer. Stage III
breast cancer typically requires induction chemotherapy to down-
size the tumor to facilitate breast-conserving surgery. Inflammatory
breast cancer, although considered stage III, is aggressive and requires
induction chemotherapy followed by mastectomy, rather than breast-
conserving surgery, as well as axillary lymph node dissection and
chest wall radiation. Prognosis is poor in women with recurrent or
metastatic (stage IV) breast cancer, and treatment options must bal-
ance benefits in length of life and reduced pain against harms from
treatment. (Am Fam Physician. 2010;81(11):1339-1346. Copyright ©
2010 American Academy of Family Physicians.)
▲ See related editorial
on page 1330.
▲ Patient information:
A handout on breast can-
cer treatment, written by
the authors of this article,
is provided on page 1347.
ILLUSTRATION BY ScOTT BOdeLL
1340 American Family Physician
Volume 81, Number 11 ◆ June 1, 2010
evaluation? is? not? usually? performed? because? nodal?
Stages I and II: Early-Stage Invasive
Modified? radical? mastectomy? has? traditionally? been?
cers.? However,? breast-conserving? surgery? has? been?
favored? more? recently.? This? therapy? involves? remov-
thetically? acceptable? to? the? patient? than? the? outcome?
from? radical? mastectomy.? Radiation? therapy? follow-
ing? breast-conserving? surgery? decreases? local? recur-
rence? and? improves? cancer-specific? survival? rates? to?
rates? equivalent? to? those? with? mastectomy.8? Breast-?
qualifications? for? consideration? of? breast-conserving?
EVALUATION OF REGIONAL LYMPH NODES
the? need? for? radiation? therapy? and? adjuvant? systemic?
numbness,? swelling,? and? decreased? mobility? in? the?
a? negative? intraoperative? sentinel? lymph? node? (SLN)?
SORT: KEY RECOMMENDATIONS FOR PRACTICE
Breast-conserving surgery should be followed by radiation therapy in women with early-stage invasive or
locally advanced breast cancer.
Sentinel lymph node biopsy results in fewer arm complications compared with axillary lymph node
dissection in the treatment of breast cancer.
Axillary lymph node dissection should be performed in women who have breast cancer with clinically
palpable lymph nodes.
Aromatase inhibitors, with or without tamoxifen, should be offered to all postmenopausal women with
hormone receptor–positive breast cancer.
Chemotherapy should be offered to all women who have breast cancer with positive lymph nodes.
Trastuzumab (Herceptin) should be offered to all women with breast cancer that is overexpressing ERBB2.
Preoperative chemotherapy for locally advanced breast cancer increases the success of breast-conserving surgery.
A 9-11, 20
A 12, 38, 40,
A = consistent, good-quality patient-oriented evidence; B = inconsistent or limited-quality patient-oriented evidence; C = consensus, disease-oriented
evidence, usual practice, expert opinion, or case series. For information about the SORT evidence rating system, go to http://www.aafp.org/afpsort.xml.
Table 1. Breast Cancer Five-Year Survival
by Stage at Diagnosis
Cancer stage Classification
I, IIa, IIb
IIIa, IIIb, IIIc
noTE: Definitions for classifying breast cancers by tumor-node-
metastasis stage are available at http://www.cancer.gov/cancertopics/
*—Data were collected through 2006 and reported using classifica-
tions of in situ, localized, regional, and distant. Current language uses
classifications of in situ, early invasive, locally advanced, and meta-
static. Interpretation of survival data must take into consideration that
treatment and terminology have changed over time.
†—Inflammatory breast cancer may be stage IIIb, IIIc, or IV.
Information from references 3 and 4.
June 1, 2010 ◆ Volume 81, Number 11?
American Family Physician 1341
a? negative? predictive? value? of? 98? percent.29,30? A? pro-
with? patients? who? have? a? negative? ALN? dissection.31?
Table 2. Typical Treatment Options for Breast Cancer by Stage
and type Primary treatment Node evaluation
Stage 0: in situ
no treatment or
(consider mastectomy if
extensive or multifocal)
and radiation therapy
Stages I and II: early-
surgery 7 and radiation
Stage III: locally advanced
noninflammatory Induction chemo-
Inflammatory ALn dissection
Stage IV: metastatic
Initial or recurrent Address patient’s
radiation therapy or
with or without
Local after breast-
MastectomyALn dissection§ Chemotherapy||Chemotherapy
Wide excisionALn dissection**
Induction chemotherapyALn dissection
ALN = axillary lymph node; SLN = sentinel lymph node.
*—SLN biopsy if clinically negative nodes; otherwise, ALN dissection is recommended.
†—Except lowest risk (i.e., tumor ≤ 1 cm, node negative).
‡—Mastectomy may be considered if tumor does not sufficiently respond to induction chemotherapy.
§—If nodes are clinically negative and SLN biopsy is done initially, SLN biopsy can be repeated; if nodes are clinically positive, ALN dissection is needed.
||—Local recurrence is often associated with distant metastases; therefore, prophylactic chemotherapy theoretically may be of benefit and is currently
¶—Benefit of adjuvant therapy is uncertain and currently being studied; until results are available, chemotherapy is generally recommended.
**—May not need to explore axilla if ALN dissection is done initially and there are clinically negative nodes with recurrence.
Information from references 6 through 22.
1342 American Family Physician
Volume 81, Number 11 ◆ June 1, 2010
Typically,? whole-breast? radiation? is? per-
randomized? controlled? trials? (RCTs)? com-
addition? to? surgery? significantly? reduced?
the? five-year? local? recurrence? rate,? regard-
(7? versus? 26? percent;? number? needed? to?
the? 15-year? breast? cancer? mortality? risk? ?
a? major? effect? on? survival? or? recurrence?
ing? brachytherapy? and? compressed? sched-
ules? of? radiation;? however,? long-term? data?
ADJUVANT SYSTEMIC THERAPIES
receive? adjuvant? systemic? therapies.? Che-
motherapy,? endocrine? therapy,? and? tissue-
targeted? therapies? enhance? definitive? local?
substantially? decreasing? cancer? recurrence?
and? disease-specific? death.? Node-positive?
Table 4? outlines? the? medications? typically?
cancer? or? with? a? tumor? larger? than? 1? cm.?
mone? receptor–positive? disease.47? Factors?
such? as? age? and? comorbidities? also? influ-
with? anthracyclines? or? taxanes? over? other?
chemotherapies,12? particularly? in? women?
tematic? review? of? 12? studies? demonstrated? ?
Table 3. Qualifying Factors for Consideration of Breast-
Conserving Surgery in the Treatment of Breast Cancer
negative surgical margins
no diffuse (inflammatory) or multicentric cancer
no malignant-appearing mammographic abnormality after surgery
no previous radiation therapy to the breast or chest wall (precludes further
*—Large tumor size in small breast may preclude the benefit of breast-conserving
surgery (relative contraindication).
Information from reference 7.
Table 4. Medications Used in the Treatment of Breast Cancer
Therapy typeMedication Typical course of treatment
IV every 14 to 21 days for four to six cycles;
used in combination with a taxane
(docetaxel [Taxotere] or paclitaxel [Taxol]),
cyclophosphamide, and/or fluorouracil
IV day 1 or days 1 and 8, every 21 to
28 days for three to eight cycles; used
in combination with cyclophosphamide
Docetaxel IV every 21 days for three to four cycles;
used in combination with doxorubicin,
epirubicin, cyclophosphamide, and/or
IV every seven to 21 days for four to
12 cycles; used in combination with
doxorubicin and cyclophosphamide
oral tablet daily for five years; used alone
or in sequence with tamoxifen36,37
oral tablet daily for at least two to five
years; used alone or in sequence with
oral tablet daily for two to five years; used
alone or in sequence with tamoxifen40,41
Gonadotropin-releasing hormone agonist
(Zoladex)months for two years42,43
Selective estrogen receptor modulators
Tamoxifenoral tablet daily for two to five years;
used alone or in sequence with an
aromatase inhibitor 36
Subcutaneously every one to three
IV with first dose of chemotherapy
regimen and then every one or three
weeks to complete one year 44-46
IV = intravenously.
Information from references 24 and 36 through 46.
June 1, 2010 ◆ Volume 81, Number 11?
American Family Physician 1343
Endocrine Therapy. Endocrine? therapies,? such? as?
SERMs,? aromatase? inhibitors,? and? gonadotropin-?
estrogen-sensitive? tumor.? In? premenopausal? women,?
menopausal? women? with? hormone? receptor–positive?
disease-specific? survival? in? patients? who? were? node?
in? overall? survival? compared? with? tamoxifen.36,38,51-53?
Tissue-Targeted Therapy. Approximately?20?to?30?per-
These? cancers? generally? have? a? worse? prognosis.? A?
humanized? anti-ERBB2? monoclonal? antibody,? trastu-
high-risk,? node-negative? breast? cancers? overexpress-
ing? ERBB2.13,14? The? combination? of? trastuzumab? and? ?
anthracyclines? must? be? used? with? caution,? however,?
Stage III: Locally Advanced
ment,? direct? involvement? of? underlying? chest? wall? or?
metastases,? and? inflammatory? breast? cancer.? Induc-
INDUCTION SYSTEMIC THERAPIES
Induction Chemotherapy.? Patients? with? LABC? who?
stage? disease.15? Preoperative? chemotherapy? downsizes?
With? induction? chemotherapy,? 75? percent? of? patients?
Preoperative? chemotherapy? increases? breast? conserva-
be? the? best? option?
Induction Endocrine Therapy. Induction? endocrine?
tors)? is? less? effective? than? chemotherapy? and? may? be?
chemotherapy-related? toxicity.? Patients? with? hormone?
receptor–positive? LABC? are? generally? best? served? by?
Induction Tissue-Targeted Therapy. There?are?few?solid?
data? about? the? use? of? tissue-targeted? therapy? (trastu-
zumab? is? recommended? for? patients? who? have? LABC?
conserving? surgery),? radiation? therapy,? or? both.? Data?
from? uncontrolled? prospective? studies? indicate? that? ?
50? to? 90? percent? of? women? with? LABC? can? be? suc-
cessfully? treated? with? breast-conserving? surgery? after?
in locally advanced breast
cancer (stage III) downsizes
the local tumor, facilitating