REVIEW

CURRENT
OPINION Current management and treatment strategies for
breast cancer
John H. Howard a and Kirby I. Bland b

Purpose of review
Breast cancer is the most common malignancy in women in the United States and the second most common
cause of cancer death in women. This review will focus on the current and clinically relevant
recommendations for breast cancer diagnosis, staging, and treatment.
Recent findings
Screening for breast cancer is based on patient history, exam, mammography, and ultrasound. In select
patient populations, MRI adds additional detection benefit. Once pathology is found, nipple-sparing
mastectomy is felt to be an oncologically well tolerated procedure for both ductal carcinoma in situ and
invasive tumors in properly selected patients. Prophylactic mastectomy rates are increasing despite no clear
survival benefit. Sentinel lymph node biopsy continues to be the staging procedure of choice, but data are
available that completion axillary dissection for a positive sentinel node may not affect outcomes.
Summary
Strategies for caring for breast cancer patients continue to evolve. Multiple variables including genetic
predisposition, disease burden, tumor markers, receptor status, and patient preference are integral to the
decision making for each individual patient.
Keywords
axillary staging, breast cancer, nipple-sparing mastectomy, surgical treatment

INTRODUCTION despite no established guidelines [3]. Current

Breast cancer is the world’s leading cause of death in indications for adjunct breast MRI include axillary
women, but breast cancer mortality rates in the adenopathy and occult primary tumor, radiographi-
United States are decreasing [1]. Improved screening cally dense breast tissue, known BRCA mutations, a
plays a role in this decrease. National Comprehen- lifetime risk greater than 20%, chest radiation, and
sive Cancer Network (NCCN) recommendations for evaluation of chest wall involvement in locally
&

breast cancer include locoregional treatment with advanced breast cancers [2–4,5 ]. A prospective
surgery and radiation, plus systemic treatment with multicenter study has shown that addition of
chemotherapy, endocrine, and biologic therapies quality-assured MRI screening may potentially
[2]. These recommendations are subject to frequent double the probability of cancer detection in a
changes in screening, surgical, and systemic strat- high-risk population (20% lifetime risk) compared
&

egies. This review discusses the recent changes and to mammography and ultrasound alone [6 ]. When
advances in breast cancer screening, prophylactic MRI is used as a surveillance tool in patients
surgery, breast conservation, surgical staging, and with known BRCA1 or BRCA2 mutations, there is a
adjuvant therapies.
a
John Wayne Cancer Institute, Santa Monica, California and bDepart-
Screening MRI ment of Surgery, University of Alabama School of Medicine, Birmingham,
Alabama, USA
Clinical breast exam, mammography, and ultra- Correspondence to Kirby I. Bland, MD, University of Alabama School
sound are the standards for screening patients for of Medicine, Boshell Diabetes Building, 1808 7th Avenue South,
breast cancer. Use of mammography for women Birmingham, AL 35233, USA. Tel: +1 205 975 5000; e-mail: kirby.
aged 39–69 has reduced mortality in this group. bland@ccc.uab.edu
The use of MRI is becoming more common as an Curr Opin Obstet Gynecol 2012, 24:44–48
additional imaging modality for breast cancer DOI:10.1097/GCO.0b013e32834da4b1

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 Treatment strategies for breast cancer Howard and Bland

significant reduction in delayed (late-stage) diagnosis [18]. Fifteen-year outcomes for both NSABP B-17
&
[7 ]. Although MRI may increase detection in high- and NSABP B-24 have confirmed that radiation in
risk populations, its benefits for normal-risk patients addition to lumpectomy for DCIS decreases the local
are not obvious. False-positive results can lead recurrence rates by 52%; adding tamoxifen improves
&&
to unnecessary patient stress and intervention. the local recurrence by another 32% [19 ]. Data from
Patients receiving an MRI for staging of their breast a multicenter prospective trial conducted by the East-
cancer are more likely to have a contralateral pro- ern Cooperative Oncology Group suggest that in
&
phylactic mastectomy (CPM) [8 ]. This relationship certain populations of patients with DCIS, wide
is unclear but may be related to additional invasive local excision alone may be adequate treatment.
procedures, biopsies, and related patient anxiety In patients with nuclear grade 1 or 2 and no or
that the patient thinks will be eliminated by CPM limited necrosis, the 5-year local recurrence rate
[9]. The randomized, controlled, multiinstitutional was 6% without radiation. However, after 7 years
COMICE trial showed that MRI findings did not the recurrence rate increases to 10.5%. This
change the surgical management of the ipsilateral increase is concerning and longer follow-up is
breast in patients whose breast cancer had been needed as recommended by the authors [20].
evaluated and diagnosed through clinical and Radiation following BCT remains the standard of
radiographic exam. The two arms of this trial had care as recommended by NCCN guidelines [2].
no difference in reoperation rate (19%) or 1-year Although invasive breast cancer is identified
rate of local recurrence. Although MRI may improve operatively in approximately 15% of patients under-
the localization of a small breast cancer, it does not going excision of DCIS, routine sentinel lymph
decrease the reoperation rates to obtain patho- node biopsy (SLNB) is not recommended because
logically negative margins as shown by this large only about 1–2% of patients with DCIS will have
&& & &
randomized trial [10 ,11 ]. invasive cancer in a sentinel node [2,15 ]. These
patients tend to have a large or palpable lesion,
microinvasion on core biopsy, high grade, and/or
Ductal carcinoma in situ and breast comedo necrosis. SLNB is indicated for these find-
conservation therapy ings and also may be indicated if mastectomy is the
With the advent of breast conservation therapy treatment of choice, because mastectomy precludes
& &
(BCT), breast surgery has trended toward mini- SLNB [21 –23 ].
mally invasive procedures. To improve the pro-
bability of negative margins in BCT, some have
advocated systematic cavity shaving after lum- Nipple-sparing mastectomy
&
pectomy to reduce re-excision rates [12 ]. Unfortu- The point of contention for nipple-sparing mastec-
nately, there is no consensus on what constitutes a tomy (NSM) is the oncologic safety of leaving the
negative margin for excision of ductal carcinoma nipple–areolar complex (NAC) while treating inva-
in situ (DCIS). A review of outcomes for DCIS sive breast cancer. Despite the lack of a randomized
treated with BCT and radiation suggests that a controlled trial showing oncologic equivalency
minimal margin of 2 mm decreases the local recur- between NSM and traditional total or skin-sparing
rence rates [13]. The tumor must not be touching mastectomy, NAC preservation is considered
the inked margins for invasive cancer. Although acceptable for carefully selected women undergoing
the discontinuous growth pattern of DCIS favors prophylactic or therapeutic mastectomy by many
& & &&
slightly wider margins [14], increasing margin nationally recognized cancer centers [24 ,25 ,26 ].
width to 5 mm does not further decrease local The criteria for selection are being expanded, as
recurrence rate [13]. there is more experience and follow-up associated
As the incidence of DCIS increases, so does the with this procedure. Contraindications include
use of MRI for its evaluation. MRI appears to be more involvement of the skin, inflammatory breast can-
sensitive than mammography in detecting multi- cer, a clinically suspicious nipple, or a NAC patho-
centric disease, but its role is unclear. Routine use of logically involved with cancer by frozen or
& && &
MRI for DCIS may lead to over treatment, worsened permanent section [24 ,26 ,27 ].
cosmetic outcomes, and potentially more unnecess- Local recurrence at the nipple is a critical end-
& &
ary mastectomies [15 ,16 ]. point for patients undergoing NSM. In two recent
Breast conservation therapy is the most com- studies, there have been no nipple recurrences when
mon treatment of DCIS in the United States [17]. intraoperative frozen section and final pathology of
The NSABP B-17 trial showed that adding breast a subareolar biopsy are confirmed to be negative for
radiation after lumpectomy for DCIS decreased cancer. Jensen et al. have confirmed these results
the rate of recurrence of DCIS and invasive cancer with an average follow-up of over 5 years suggesting

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 Breast cancer

that NSM is a durable and well tolerated treatment contributing factors are tumor stage, histopatho-
& &&
for invasive breast cancer [24 ,26 ]. A subareolar logy, family history, improved reconstruction tech-
& &
biopsy to confirm that the nipple is not involved niques, and earlier detection with MRI [8 ,30 ,
& && &
must be performed during this procedure. If the 31 ,32 ,33 ]. Although prophylactic mastectomy
biopsy is positive on either frozen section or final reduces the incidence of breast cancer, its influence
pathology, the NAC must be resected. It is important on disease-specific survival is unclear, particularly in
& &&
to counsel the patient regarding this issue, as 10.7– average-risk patients [8 ]. Bedrosian et al. [36 ]
14.2% of nipples will have involvement and need to suggested that CPM may be associated with a small
&& &
be resected [26 ,28 ]. Frozen section is very specific improvement in the 5-year breast cancer survival of
&
for nipple involvement but not as sensitive [29 ]. If young women with early stage, estrogen receptor-
final pathology is positive for nipple involvement, negative breast cancer. Because of its relatively short
then a second procedure for NAC removal is needed. median follow-up (47 months) and the expected
Tumor size, location, tumor type, lymphovascular 2.5% 5-year risk of a contralateral breast cancer
invasion, lymph node status, histologic grade, (CBC) in this population, this study has been
receptors status, HER-2 amplification, and multi- criticized for a selection bias favoring younger,
&
centric/multifocal tumors have been associated with healthier patients [37 ]. Another retrospective study
&
nipple involvement [28 ]. with much longer follow-up reported improved
Although there are only retrospective data to overall and disease-free survival, and decreased
validate NSM for the treatment and prevention of CBC in patients undergoing CPM for high-risk
&
breast cancer, this technique has been shown to have breast cancer [38 ].
at least equivalent locoregional oncologic outcomes A woman’s decision to undergo CPM is complex
and better cosmetic satisfaction rates compared to and multifactorial. Patients with genetic mutations,
& &
traditional surgical therapy [24 , 27 ]. The improved family history, or high-risk lesions may benefit from
cosmesis of NSM will contribute to the popularity of CPM, but there is growing evidence that better
this procedure and its use in practice will be patient education for average-risk patients could avoid
&
driven. Prospective data and proper patient selection unnecessary and nonrisk-reducing surgeries [39 ].
for NSM will be significant in determining long-term
oncologic outcomes and for the overall acceptance of
this procedure. Axillary staging
The introduction of SLNB for axillary staging
changed the surgical management of invasive breast
Prophylactic mastectomy cancer. A total of 50–65% of patients with a positive
Improved screening techniques and neoadjuvant sentinel node have no additional axillary disease.
regimens have increased the number of candidates The necessity of completion axillary lymphadenec-
for BCT. However, there has also been an increase in tomy in patients with sentinel node metastasis was
& &
the number of patients undergoing CPM [8 ,30 ]. addressed by the ACOSOG Z0011 trial, which pro-
These patients have been diagnosed with DCIS or duced arguably the most significant data on breast
invasive breast cancer but are not necessarily at high cancer treatment in the past 18 months. In this
risk for developing a contralateral breast cancer prospective trial, 891 patients with T1 or T2 breast
& & && &
[8 ,31 ,32 ,33 ]. The increased use of CPM in DCIS cancer, one or two sentinel lymph nodes positive
patients is particularly puzzling because NSABP B-24 for metastatic disease, and no palpable axillary lym-
findings show that surveillance, endocrine treat- phadenopathy were randomized to completion axil-
ment, and radiation significantly decrease the risk lary lymph node dissection or SLNB alone. All
of contralateral breast cancer and are associated with patients had tangential whole-breast irradiation,
a breast cancer survival rate of 98% [34]. but systemic therapy was at the discretion of the
The most convincing reason for prophylac- treating physician. Despite early study closure
tic mastectomy is known BRCA 1/2 mutation. because of low accrual, the Z0011 trial was the
&&
Domchek et al. [35 ] recently showed that BRCA- largest phase III study to demonstrate no benefit
positive patients had a lower risk of breast cancer for completion axillary lymph node dissection for
after prophylactic mastectomy, plus a lower risk limited nodal disease. There was no difference in
of breast cancer death when treatment included breast recurrence, nodal recurrence, or 5-year rates
salpingo-oopherectomy. However, because most of overall and disease-free survival between the two
&&
patients undergoing CPM do not have a known arms [40 ]. It is not clear whether results would
genetic defect, the decision for CPM may reflect apply to patients with larger tumors or more exten-
socioeconomic status (young white women are sive nodal involvement. Other retrospective studies
the most likely to undergo CPM). Other likely and reviews suggest that further axillary dissection

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 Treatment strategies for breast cancer Howard and Bland

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&
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 Breast cancer

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This study helps determine that socioeconomic factors may be more significant This prospectively randomized trial shows that occult SLNB metastases found by
than tumor biology in which patients will choose CPM. IHC give no clinically significant survival advantage and should not be performed in
32. Tuttle TM, Abbott A, Arrington A, Rueth N. The increasing use of prophylactic early stage breast cancer.
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