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Review |

Breast Cancer:  A Review for the General Surgeon FREE

Cindy B. Matsen, MD1; Leigh A. Neumayer, MD, MS1,2
[+] Author Affiliations
1Department of General Surgery, University of Utah, Salt Lake City
2Department of Surgery, Huntsman Cancer Hospital, University of Utah, Salt Lake City
JAMA Surg. 2013;148(10):971-980. doi:10.1001/jamasurg.2013.3393.
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Published online

Breast cancer care is complex and requires a multidisciplinary approach. In this study, we provide an overview of current practices for the diagnosis and treatment of breast cancer for surgical practitioners who do not focus on this disease. We include studies published in high-impact, peer-reviewed journals that have informed or altered the standard of care, with preference given to large, multicenter, randomized clinical trials when available. Our study highlights that the surgical management of breast cancer has changed dramatically over the past decades. As our understanding of the disease process increases, practice guidelines will continue to evolve.

Figures in this Article

Breast cancer is the most commonly diagnosed cancer in women in the United States and the second most deadly.1 One in 8 women will be diagnosed with breast cancer in their lifetime. Surgical management of breast cancer continues to evolve and remains a key component of treatment and cure. This review is intended to provide an overview of the diagnosis, treatment, and follow-up of patients with breast cancer for the general surgeon.

Many risk factors for the development of breast cancer have been identified.2 The most commonly used tool for risk assessment is the Breast Cancer Risk Assessment Tool (Gail model), developed by the National Cancer Institute and the National Surgical Adjuvant Breast and Bowel Project (NSABP),3 and has been updated recently to better estimate risk for African American, Pacific Islander, and Hispanic women.46 It includes age, race, previous breast biopsy and biopsy results, age at menarche, age at first live birth, and first-degree relatives with breast cancer. This tool can help guide clinical decision making and assist in making individualized recommendations (http://www.cancer.gov/bcrisktool/).

Chemoprevention with tamoxifen or raloxifene hydrochloride should be considered for all patients with lobular carcinoma in situ, atypical ductal hyperplasia, a Gail model risk of more than 1.7%, or BRCA1 (113705 OMIM) and BRCA2 (600185 OMIM) mutations. The STAR (Study of Tamoxifen and Raloxifene) trial showed that both tamoxifen and raloxifene reduced the risk of invasive breast cancer by 50%, but only tamoxifen has been proved to reduce the risk of developing ductal carcinoma in situ (DCIS).79

Lobular carcinoma in situ and atypical lobular hyperplasia are collectively known as lobular neoplasia.10 Lobular neoplasia is a histologic finding of cellular atypia that confers an 8- to 10-fold increased risk for the development of invasive breast cancer in either breast.11 Women with lobular carcinoma in situ should be considered for treatment with tamoxifen, which has been shown to reduce risk by 56%.12

Atypical ductal hyperplasia is a premalignant lesion that confers a 4 to 5 times increased risk for breast cancer. Chemoprevention with tamoxifen is effective in reducing the risk by 86%.

Known genetic mutations are found in 5% of women with familial breast cancer and include the high-penetrance genes TP53 (Li-Fraumeni syndrome) (191170 OMIM), PTEN (Cowden syndrome) (601728 OMIM), and BRCA mutations as well as many lower-penetrance genes.13 Of these, the BRCA gene mutations are the most prominent. Another 10% of breast cancers are familial with no known genetic mutation.14 The National Comprehensive Cancer Network has published guidelines for referral for further testing and genetic counseling. Criteria in a patient without a known diagnosis of breast cancer include 2 or more primary breast cancers on the same side of the family (in the same individual or 2 separate individuals), 1 or more ovarian cancers on the same side of the family, breast cancer in a first- or second-degree relative diagnosed before age 45 years, known mutation in a breast cancer susceptibility gene within the family, and male breast cancer.15 Details of the full guidelines can be found on the National Comprehensive Cancer Network website.15 Patients with high familial risk are recommended to undergo genetic counseling and potentially genetic testing, increased surveillance, and possibly chemoprevention. They should also be presented with the options of prophylactic bilateral mastectomy and oophorectomy, which are associated with improved breast cancer–specific and overall survival.14,16

The BRCA genes were first described in 1994.17,18 Their discovery has provided significant insight into the biology of breast cancer. Both BRCA1 and BRCA2 mutations confer a 60% to 80% lifetime risk for the development of breast cancer and are associated with other malignant neoplasms, including ovarian cancer. BRCA1 is slightly more strongly associated with ovarian cancer than BRCA2, while BRCA2 is more highly associated with pancreatic cancer and male breast cancer.19 At a minimum, women with known BRCA mutations should undergo increased surveillance to include annual mammography and annual bilateral breast magnetic resonance imaging.15 In addition to increased surveillance, tamoxifen may provide risk reduction in patients with the BRCA gene, although this has never been addressed specifically in clinical trials. Alternatively, patients with these mutations can be considered for bilateral mastectomy and bilateral oophorectomy.20

Despite randomized trials showing decreased mortality with screening mammography,2123 there has been considerable controversy surrounding screening guidelines in the United States in the past few years. The most recent American Cancer Society recommendations advocate yearly screening mammography starting at age 40 years and clinical breast examinations every 3 years for women aged 20 to 40 years and yearly after age 40 years.24 The US Preventive Services Task Force guidelines, published in 2009, recommend biennial screening mammography for women aged 50 to 74 years, discourages breast self-examinations, and concludes that the evidence is insufficient to support a recommendation for clinical breast examination in addition to mammography in women aged 40 to 50 years.25,26 This has caused considerable confusion among patients and debate among practitioners.27 However, many groups (American College of Surgeons, American College of Radiology, etc) endorse the screening guidelines recommended by the American Cancer Society.

Screening mammography is far from a perfect test, with a sensitivity that may be as low as 70% in women younger than 50 years.28,29 The evidence for the benefits of screening mammography in women older than 50 years is clear, with mortality reduced by up to one-third.30 False positives are a significant problem and are estimated to be up to 30% in screened populations, leading to costly invasive procedures and psychological stress for the patient.31 However, for every 2000 women screened, 1 will have her life prolonged and 10 will undergo unnecessary procedures.32 Most practitioners continue to follow the American Cancer Society guidelines, and mammography rates have not significantly changed since the publication of the guidelines from the US Preventive Services Task Force.33 Regardless of the guidelines used, any screening regimen requires patient education on the risks and benefits.29,34 Underuse of mammographic screening programs is an ongoing public health concern.35 Screening programs have been shown to be effective in reducing mortality among the uninsured and underinsured low-income women.36 The guidelines for the use of digital mammography and magnetic resonance imaging have evolved dramatically during the past decade. Both the American Cancer Society and the US Preventive Services Task Force guidelines include these modalities in their recommendations, although with different interpretations of their usefulness. Digital mammography is more accurate than film mammography in women who are younger than 50 years, have dense breasts, and are premenopausal.28,37 Magnetic resonance imaging is now recommended as a screening modality in young women who are at high risk for developing breast cancer, as defined by their family history or other factors that, when combined, confer a lifetime risk of more than 20%.38,39 It is useful in evaluating the response to neoadjuvant treatment but rarely reduces the number of operations or changes the surgical treatment plan, and accuracy varies with molecular phenotype and type of neoadjuvant treatment.4042 Emerging screening modalities are currently under investigation. Breast tomosynthesis is thought to be equivalent to standard mammography, and automated whole-breast ultrasound is reliable for detecting lesions larger than 1.2 cm. Further study on a larger scale is warranted.43,44

Once a patient has a suspicious abnormality on screening mammography, the first step should be diagnostic mammography with or without ultrasound; if found on magnetic resonance imaging, the next step is ultrasound. Confirmed abnormalities on diagnostic mammography or magnetic resonance imaging should be evaluated with image-guided core needle biopsy. Figure 1 shows a simplified algorithm for the surgical management of biopsy-confirmed lesions.

Place holder to copy figure label and caption
Figure 1.
Simplified Algorithm for Surgical Management of Biopsy-Proved Breast Disease

ADH indicates atypical ductal hyperplasia; ALH, atypical lobular hyperplasia; DCIS, ductal carcinoma in situ; SLNB, sentinel lymph node biopsy; and XRT, radiation therapy.

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Atypical lobular hyperplasia is associated with an underlying cancer in 13% of specimens,45 and when atypical ductal hyperplasia is found on core needle biopsy, the patient should undergo excisional biopsy since up to 30% of patients will have DCIS or invasive cancer on excisional biopsy.4648 Several other histologic findings on core needle biopsy may be associated with a malignant neoplasm. These include flat epithelial atypia (which is usually found in association with atypical ductal hyperplasia or DCIS), papillary lesions, and radial scar. These findings should be discussed with a multidisciplinary team and a patient-specific treatment plan formulated.46,49 In general, if atypia or a radial scar is found on core needle biopsy, excisional biopsy should be considered.

Tissue is sent for histopathologic examination with hormone receptors and HER-2/neu staining if a cancer is found. Estrogen receptor (ER) and progesterone receptor status and HER-2/neu affect both prognosis and therapeutic options.50

Invasive ductal carcinoma is by far the most common pathologic diagnosis, representing 80% of all breast cancers. Invasive lobular carcinoma, the second most common, represents 10% of breast cancers. Inflammatory breast cancer is an aggressive subtype that presents with swelling and erythema of the breast. Because it represents the spread of cancer into the dermal lymphatics, it can be diagnosed by punch biopsy of the skin in the clinic but is primarily a clinical diagnosis based on the rapid progression of skin changes. Almost all women with this subtype have nodal involvement at the time of diagnosis, and one-third have distant metastases.51

Ductal carcinoma in situ is a cancer that has not violated the basement membrane—in other words, it is preinvasive cancer. The incidence of DCIS has escalated with increased screening and improvement in imaging modalities, although this alone does not entirely explain the rise. It is most often seen as calcifications on mammogram.52 The Van Nuys Prognostic Indicator can be used to predict risk of local recurrence.53 Poor prognostic indicators for local recurrence include high grade, comedonecrosis, positive margins, and young age.

Other histologic variants (medullary, tubular, papillary, and mucinous) generally are treated similarly to invasive ductal carcinoma, although they often have a better prognosis.54,55 Two other rare but important types of breast cancer are Paget disease and phyllodes tumor.42 Paget disease manifests with a red, scaly, itchy nipple and is diagnosed by biopsy of the affected area. The most recent studies show that between 85% and 92% of women with Paget disease have an underlying breast cancer.56,57 Every diagnosis of Paget disease should be followed by a search for the cancer. Phyllodes tumor (aka cystosarcoma phyllodes) is a rare breast neoplasm that is a fibroepithelial tumor originating from the periductal stroma.58 Phyllodes tumors are graded as benign, borderline, or malignant. They tend to recur locally, so even benign phyllodes tumors should be excised with a wide (≥1-cm) margin.58

For decades, invasive breast cancer has been characterized by grade (1, 2, or 3) and by whether the tumor cells have receptors for estrogen and/or progesterone. Expression of the protein HER-2/neu is also routinely noted since each of these characteristics is used to determine the need for and type of systemic therapy. Most invasive breast cancers have receptors for estrogen and progesterone (hormone-sensitive cancers).

Molecular subtyping is now widely used clinically for invasive breast cancer. The Oncotype DX (Genomic Health) is a 21-gene assay for ER-positive, lymph node–negative, formalin-fixed tissue and predicts the risk of recurrence and response to tamoxifen.5961 Recently, it has been shown to be useful in lymph node–positive patients as well. This test may spare some patients from chemotherapy.62 MammaPrint (Agendia) is a 70-gene assay for ER-positive and ER-negative, lymph node–negative, formalin-fixed, paraffin-embedded tissue that predicts the risk of recurrence and is used to stratify patients who would benefit from adjuvant chemotherapy.63 The PAM 50 Breast Cancer Intrinsic Classifier (ARUP Laboratories) is a 50-gene set assay for early-stage, lymph node–negative, formalin-fixed tissues that classifies breast cancer into 1 of 5 accepted molecular subtypes.64,65 These profiles can be used to predict risk of recurrence and response to adjuvant and neoadjuvant chemotherapeutics, as well as provide general prognostic information.6567

The treatment of breast cancer is multidisciplinary and can include surgery, radiation, and systemic therapy (chemotherapy, hormonal therapy, or biologic therapy). Several factors should be used to determine not only the treatments to be considered but also the sequencing of the therapies. Most patients with early-stage breast cancer (DCIS and small tumors that are clinically lymph node negative) will proceed to surgery first. In patients with large tumors, skin involvement, or bulky nodal disease, many advocate neoadjuvant chemotherapy since response to chemotherapy provides prognostic information. Patients with inflammatory breast cancer should always receive chemotherapy first. Radiation is given after chemotherapy and surgery except in patients undergoing partial breast irradiation, when it is given after surgery but before chemotherapy. For older or infirm patients with hormone-positive tumors, endocrine therapy can be used as a sole treatment.

Ductal carcinoma in situ warrants special mention. Management of the breast in DCIS is similar to early-stage invasive breast cancer, although low-risk patients may undergo simple lumpectomy only. Approximately 15% of patients with DCIS will have an associated invasive cancer.68 As stated previously, for patients with ER-positive DCIS, tamoxifen is useful for decreasing the risk of ipsilateral invasive cancer.

Surgery has been the primary modality for the treatment of breast cancer for centuries. Halsted, who first performed a radical mastectomy in 1882, published his results in 1894.69 The Halstedian approach remained the gold standard for the surgical management of breast cancer for nearly 80 years. For the past 30 years, surgical management of the breast has transitioned from radical approaches to less extreme, breast-conserving procedures, although recently there has been a trend of increasing mastectomy rates for unclear reasons.70 The evolution toward less radical procedures has been evidence based. One randomized trial, NSABP B-04, which started in 1971, compared radical mastectomy without radiation vs simple mastectomy with radiation vs simple mastectomy without radiation. It enrolled 1765 patients over 126 months, and the randomization scheme was based partly on nodal status, with patients with “clinically” lymph node–positive disease randomized to radical mastectomy or simple mastectomy with radiation. “Clinically” lymph node–negative patients were randomized to any of the 3 groups. No survival, disease-free, or distant disease–free differences were seen among the groups, and this study brought the era of radical mastectomy to an end.71

Another trial, NSABP B-06, involved a randomized comparison of mastectomy vs lumpectomy alone vs lumpectomy with radiation for patients who had stage I or II disease with tumors less than 4 cm. In total, 2163 women were enrolled from 1976 through 1984, and axillary dissection was performed in all groups. The 20-year follow-up of 1851 patients was published in 2002. There were no differences in overall survival but significant differences in recurrence, with the lumpectomy-alone groups having a 39.2% rate of recurrence at 20 years72 (Figure 2 and Figure 3). Thus, the standard of care for breast-conserving surgery has become lumpectomy with radiation. Absolute contraindications to lumpectomy include prior radiation therapy, pregnancy, multicentric tumor, inability to obtain clear margins (large tumor or invasion into adjacent structures), and physical inability to tolerate radiation therapy. Relative contraindications include multifocal tumor, connective tissue disease, and a large tumor to breast size ratio. Recurrences should be managed with mastectomy.

Place holder to copy figure label and caption
Figure 2.
Twenty-Year Follow-up of NSABP B-06 Survival Curves

Disease-free survival (A), distant disease–free survival (B), and overall survival (C) among 589 women treated with total mastectomy, 634 treated with lumpectomy alone, and 628 treated with lumpectomy plus irradiation. P values above the lines are for 3-way comparison among the groups. P values below the lines are for 2-way comparisons between lumpectomy alone or with irradiation and total mastectomy. NSABP B-06 indicates National Surgical Adjuvant Breast and Bowel Project B-06. Reproduced with permission from Fisher et al.72

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Figure 3.
Twenty-Year Follow-up of NSABP B-06 Ipsilateral Breast Recurrence in Lumpectomy and Lumpectomy Plus Irradiation Groups

Cumulative incidence of a first recurrence of cancer in the ipsilateral breast during 20 years of follow-up among 570 women treated with lumpectomy alone and 567 treated with lumpectomy plus breast irradiation. The data are for women whose specimens had tumor-free margins. NSABP B-06 indicates National Surgical Adjuvant Breast and Bowel Project B-06. Reproduced with permission from Fisher et al.72

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Skin-sparing mastectomy has been shown to be oncologically safe in selected patients.73 Nipple-sparing mastectomy is more controversial but gaining in acceptance.74 Most current studies support its safety with up to 5 years of follow-up, but long-term follow-up is not yet available.7577

The use of contralateral prophylactic mastectomy has increased in recent years. The reasons for this are multifactorial but in part are driven by patients’ misunderstanding of the overall risk of developing a contralateral cancer.78,79 Contralateral prophylactic mastectomy is most justified in patients with a high lifetime risk for developing contralateral breast cancer (BRCA positive, strong family history, or a young patient with biologically aggressive disease).

In any discussion of surgical management of the axilla, it is important to note that removal of lymph nodes conveys no treatment benefit to the patient and is for staging and prognosis only. As with treatment of the breast, management of the axilla has trended toward doing less over time. The groundbreaking work by Morton et al80 in sentinel lymph node biopsy in melanoma paved the way for application of this technique to other malignant neoplasms. Its use in breast cancer was established by Guiliano et al81,82 and in the landmark study NSABP B-32.83 The NSABP B-32 study compared sentinel lymph node biopsy followed by axillary dissection with sentinel lymph node biopsy followed by axillary dissection only if the sentinel lymph node(s) was positive. This advancement revolutionized surgical treatment of the axilla, and for more than a decade, the standard of care remained sentinel lymph node biopsy in the clinically negative axilla followed by axillary lymph node dissection in those with positive sentinel lymph nodes. It was known, however, from NSABP B-32 and other studies that a large number of women with a positive sentinel lymph node(s) would not have any other positive lymph nodes on completion dissection. Nomograms to predict the likelihood of additional (nonsentinel) positive lymph nodes were developed and used widely in the clinic.84,85 With increasing use of adjuvant therapies, patients who underwent removal of sentinel lymph nodes only without completion axillary dissection did not have high regional recurrence rates, although this had not been proved in a randomized fashion.86 All of this begged the question of how to minimize overtreatment of the axilla and avoid the possible attendant complications, most notably lymphedema and chronic pain.87 The American College of Surgeons Oncology Group trial Z0011 showed that, in select patients, completion axillary dissection could be safely omitted.88,89 Patients with stage I or II breast cancer undergoing breast-conserving therapy with less than 3 positive lymph nodes had no differences in survival or recurrence at a mean 6.3-year follow-up. This study has led to a widespread change in the management of the axilla in patients who meet the selection criteria.90,91 To reiterate, in patients with tumors less than 5 cm, clinically lymph node–negative axilla, less than 3 positive lymph nodes, and treatment with breast-conserving therapy (to include whole-breast radiation) and adjuvant systemic hormonal therapy or chemotherapy, completion axillary lymph node dissection can be safely omitted.

Sentinel lymph node biopsy is indicated in any invasive cancer with a clinically negative axilla. Studies also support sentinel lymph node biopsy in patients undergoing mastectomy for DCIS or high-risk lesions.92 The NSABP B-27 trial and other studies showed sentinel lymph node biopsy to be accurate after neoadjuvant therapy.93,94

Surgery remains the most accurate method of staging nonmetastatic malignant tumors. The staging system for breast cancer follows the TNM system, with the most recent system approved by the American Joint Committee on Cancer shown in the Table.95 Prognostication based on size and nodal status without an understanding of the underlying individual tumor biology is imperfect.

Table Graphic Jump LocationTable.  Simplified AJCC Breast Cancer Staging Adapted From the 7th Editiona

In the era of molecular profiling, the decision to offer chemotherapy is increasingly based on analysis of an individual’s tumor.67 Aside from the molecular profile, relative indications for chemotherapy include large tumor size (>2 cm), positive lymph nodes, ER-negative and progesterone receptor–negative tumors, HER-2/neu–positive tumors, and inflammatory breast cancer.60,67 Anthracycline-based regimens have been shown to be superior to methotrexate-based regimens, although the adverse effects are more substantial.9698 Anthracyclines are associated with cardiotoxicity and should be used cautiously or avoided in older patients with cardiac disease, especially if used in combination with trastuzumab.99101 The addition of taxanes to chemotherapy has been shown to significantly improve outcomes and is now used for standard treatment.102104

Indications for neoadjuvant therapy have expanded greatly in the past 10 years, with published international consensus guidelines.105 One trial, NSABP B-27, showed that patients with a pathologic complete response to neoadjuvant chemotherapy have improved disease-free and overall survival.106

Radiation after lumpectomy is associated with a lower local recurrence rate.72 In patients who have had a mastectomy, large tumor size (>5 cm), 4 or more positive lymph nodes, close margins, or inflammatory breast cancer are all indications for adjuvant radiation.107 Women with recurrent cancer who have not had prior radiation should also be offered this therapy. Radiation typically consists of whole-breast radiation given for 6 to 6½ weeks, including a boost dose. Accelerated partial breast irradiation has recently been introduced, and the American Society for Radiation Oncology has published guidelines for the use of this technology.108 While there are multiple delivery systems for this therapy, not all have been evaluated in clinical trials. The MammoSite device (Hologic), which involves placement of a balloon catheter into the lumpectomy site, has been evaluated in the American Society of Breast Surgeons MammoSite Breast Brachytherapy Registry Trial.109 The Intrabeam device (Carl Zeiss), used to deliver radiation to the tumor bed intraoperatively, has been evaluated in the Targeted Intraoperative Radiotherapy for Breast Cancer Trial (TARGIT).110 When compared with whole-breast radiation, there were similar local recurrence rates with both devices. Concerns about increased seroma formation and wound problems with these techniques have yet to be resolved.111113 Hypofractionation, in which larger doses of radiation are given in fewer treatments, is also an area of great interest that needs further study. Multiple ongoing trials should resolve some of the remaining questions regarding the appropriate use of accelerated partial breast irradiation and hypofractionation.113

Estrogen receptor was first identified in the late 1950s, and endocrine therapies have been used in the treatment of breast cancers for more than 60 years. All patients with ER-positive tumors should be treated with an adjuvant ER blockade. Progesterone receptor positivity, even in ER-negative tumors, is a strong predictor of response to tamoxifen.50 The most widely used and studied drug in this category is tamoxifen. The current recommendation is for 5 years of treatment, although a longer course of 10 years has been shown to further reduce the risk of recurrence and mortality.114 Tamoxifen was compared with the aromatase inhibitor anastrozole in the ATAC (Arimidex, Tamoxifen, Alone or in Combination) trial.115 This study showed anastrozole to be superior (prolonged disease-free survival, increased time to recurrence, and decreased distant metastases and contralateral breast cancers) with fewer adverse effects compared with tamoxifen when used in postmenopausal women with estrogen-responsive cancers.

Thus, aromatase inhibitors are the hormone-blocking agents of choice in postmenopausal women. Aromatase inhibitors should not be used in premenopausal women, in whom estrogen is produced mainly in the ovaries, since it activates the hypothalamic-pituitary-adrenal axis, which increases ovarian androgen production and counteracts the effects of the drug. Targeted biologic therapies are perhaps more widely used in breast cancer than in any other disease. Amplification of the HER-2/neu receptor in breast cancer was first recognized in breast cancer cell lines. It was then evaluated in human breast cancers, and its presence conferred a poor prognosis.116 It is associated with higher rates of recurrence, relative resistance to hormonal therapy, and resistance to some chemotherapeutics.117 All pathology reports should include HER-2/neu status by immunohistochemistry, with equivocal (ie, 2+) results confirmed by fluorescence in situ hybridization analysis. The development of the monoclonal antibody against HER-2/neu, trastuzumab, revolutionized treatment for the 15% to 20% of patients with Her-2–positive breast cancers. Multiple studies have proven the efficacy of this drug in dramatically improving outcomes in Her-2–positive cancers.118122 Trastuzumab is recommended for use in patients with confirmed amplification of the HER-2/neu gene (3+ on immunohistochemistry or fluorescence in situ hybridization confirmed). Patients with Her-2/neu–positive tumors are treated with trastuzumab for 1 year.

Additional HER-2/neu-targeted drugs have been developed. Pertuzumab inhibits HER-2/neu receptor dimerization and is complementary to trastuzumab when used in combination.123,124 Lapatinib targets the epidermal growth factor receptor and HER-2/neu but has inferior outcomes to trastuzumab when used alone.125 Trastuzumab is associated with risk of heart failure, and patients should undergo an evaluation of cardiac function before starting therapy.126,127

The use of vascular endothelial growth factor inhibitors, such as bevacizumab, for the treatment of breast cancer remains controversial.128 A discussion of this topic is beyond the scope of this review.

The American Society of Clinical Oncology recommends that patients be seen in the clinic every 3 to 6 months for the first 3 years, every 6 to 12 months in years 4 and 5, and annually thereafter. Patients who have undergone breast-conserving surgery with radiation should have their first posttreatment mammogram 1 year after the mammogram that led to diagnosis but no earlier than 6 months after the completion of radiation therapy. Mammograms should be performed annually thereafter.129

Breast cancer is a common but extremely complex disease. Careful consideration should be given to the unique nature of each tumor and patient. Every newly diagnosed breast cancer should be presented at a multidisciplinary conference to ensure the optimal management by all specialties involved. Treatment for breast cancer will continue to evolve; further improvements in outcomes will likely be based on the development of targeted therapies.

Accepted for Publication: February 27, 2013.

Corresponding Author: Leigh A. Neumayer, MD, MS, Department of Surgery, Huntsman Cancer Hospital, University of Utah, 1950 Circle of Hope, Room N6335, Salt Lake City, UT 84112 (leigh.neumayer@hsc.utah.edu).

Published Online: August 28, 2013. doi:10.1001/jamasurg.2013.3393.

Author Contributions: Study concept and design: All authors.

Acquisition of data: All authors.

Analysis and interpretation of data: All authors.

Drafting of the manuscript: All authors.

Critical revision of the manuscript for important intellectual content: All authors.

Administrative, technical, and material support: Neumayer.

Study supervision: Neumayer.

Conflict of Interest Disclosures: None reported.

Correction: This article was corrected on November 11, 2013, to fix an inaccurate number in the text.

American Cancer Society. Breast cancer: facts & figures 2011-2012. http://www.cancer.org/acs/groups/content/@epidemiologysurveilance/documents/document/acspc-030975.pdf. Accessed October 11, 2012.
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Figures

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Figure 1.
Simplified Algorithm for Surgical Management of Biopsy-Proved Breast Disease

ADH indicates atypical ductal hyperplasia; ALH, atypical lobular hyperplasia; DCIS, ductal carcinoma in situ; SLNB, sentinel lymph node biopsy; and XRT, radiation therapy.

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Figure 2.
Twenty-Year Follow-up of NSABP B-06 Survival Curves

Disease-free survival (A), distant disease–free survival (B), and overall survival (C) among 589 women treated with total mastectomy, 634 treated with lumpectomy alone, and 628 treated with lumpectomy plus irradiation. P values above the lines are for 3-way comparison among the groups. P values below the lines are for 2-way comparisons between lumpectomy alone or with irradiation and total mastectomy. NSABP B-06 indicates National Surgical Adjuvant Breast and Bowel Project B-06. Reproduced with permission from Fisher et al.72

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Figure 3.
Twenty-Year Follow-up of NSABP B-06 Ipsilateral Breast Recurrence in Lumpectomy and Lumpectomy Plus Irradiation Groups

Cumulative incidence of a first recurrence of cancer in the ipsilateral breast during 20 years of follow-up among 570 women treated with lumpectomy alone and 567 treated with lumpectomy plus breast irradiation. The data are for women whose specimens had tumor-free margins. NSABP B-06 indicates National Surgical Adjuvant Breast and Bowel Project B-06. Reproduced with permission from Fisher et al.72

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Tables

Table Graphic Jump LocationTable.  Simplified AJCC Breast Cancer Staging Adapted From the 7th Editiona

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