An overview of breast cancer Author Daniel F Hayes, MD Section Editor Julie R Gralow, MD Deputy Editor Rachel Lerner, MD,

MS Last literature review version 19.1: enero 2011 | This topic last updated: febrero 18, 2011 (More) INTRODUCTION Breast cancer is the most common female cancer in the US, the second most common cause of cancer death in women, and the main cause of death in women ages 40 to 59 [1]. EPIDEMIOLOGY AND RISK FACTORS Important risk factors for breast cancer are age, gender, hormonal factors, and family history. Although a family history of breast and/or ovarian cancer is common in patients diagnosed with breast cancer, less than ten percent of all breast cancers are associated with germline mutations. The epidemiology and risk factors for breast cancer and genetics and management of hereditary breast cancer syndromes are discussed separately. (See "Epidemiology and risk factors for breast cancer".) (See "Characteristics of hereditary breast and ovarian cancer syndromes".) (See "Genetic testing for hereditary breast and ovarian cancer syndrome".) (See "Management of BRCA1 and BRCA2 hereditary breast and ovarian cancer syndrome".)

Chemoprevention is an option for premenopausal and postmenopausal women who are high risk for breast cancer (by virtue of their age, family history, or personal history of lobular carcinoma in situ). (See "Selective estrogen receptor modulators for the prevention of breast cancer".) In the modern era, most breast cancers are diagnosed as a result of an abnormal mammogram. Screening recommendations and the evidence in support of screening are discussed separately. (See "Screening for breast cancer".) DIAGNOSIS The diagnostic evaluation of a patient with suspected breast cancer includes screening and diagnostic breast imaging and breast biopsy. Breast cancer is classified according to the American Joint Committee on Cancer and the International Union for Cancer Control (AJCC-UICC) TNM breast cancer staging system (table 1) [2]. (See (See (See (See "Breast lumps and other common breast problems".) "Diagnostic evaluation of women with suspected breast cancer".) "Breast biopsy".) "Initial work-up and staging after a new diagnosis of breast cancer".)

There are several histologic types of breast cancer, but infiltrating ductal carcinoma is the most common type of invasive breast cancer, accounting for 70 to 80 percent of invasive lesions.

(See (See (See (See (See

"Pathology of breast cancer: The invasive carcinomas".) "Breast sarcomas".) "Paget disease of the breast".) "Phyllodes tumors of the breast".) "Breast lymphoma".)

The in situ carcinomas of the breast, ductal carcinoma in situ (DCIS) and lobular carcinoma in situ (LCIS), represent a heterogenous group of proliferative lesions confined to the breast ducts and lobules, and their epidemiology, pathology, and management are discussed separately. (See "Pathology of breast cancer: The in situ carcinomas".) (See "Breast ductal carcinoma in situ and microinvasive carcinoma".) (See "Lobular carcinoma in situ of the breast".)

Assay of hormone receptors (estrogen [ER] and progesterone [PR] receptors) is an important component of the pathologic evaluation of breast cancer, for both prognostic and predictive purposes, as patients with hormone receptor-positive tumors benefit from the addition of endocrine treatments. All primary tumors should also be assayed for human epidermal growth factor receptor 2 (HER2) expression; approximately 20 percent have high levels of overexpression. High levels of HER2 expression (3+ by immunohistochemical staining or an amplified HER2 gene copy number by fluorescence in situ hybridization [FISH]) represent an important predictive factor, identifying those patients who might benefit from treatments that target HER2, such as trastuzumab. (See "Hormone receptors in breast cancer: Measurement and clinical implications".) (See "HER2 and predicting response to therapy in breast cancer".)

Other prognostic factors for early breast cancer include the status of the draining axillary lymph nodes, tumor size, tumor grade, markers of an elevated proliferative rate, and circulating tumor cells. (See "Measurement of prognostic factors in breast cancer".) TREATMENT FOR EARLY STAGE BREAST CANCER The treatment of early breast cancer includes the treatment of locoregional disease with surgery, radiation therapy, or both, and the treatment of systemic disease with one or a combination of chemotherapy, endocrine therapy, or biologic therapy. The need for, timing, and selection of therapy are based upon tumor variables such as histology, stage, and tumor markers; patient variables such as age, menopausal status, and comorbid conditions; as well as patient preference, such as a desire for breast preservation. Neoadjuvant systemic therapy The indications and use of neoadjuvant or preoperative therapy for early breast cancer are discussed separately. (See "Neoadjuvant systemic therapy for breast cancer: Indications, pretreatment evaluation, and response".)

(See "Neoadjuvant systemic therapy for breast cancer: Neoadjuvant chemotherapy".) (See "Neoadjuvant systemic therapy for breast cancer: Neoadjuvant endocrine therapy".) (See "Neoadjuvant systemic therapy for breast cancer: Locoregional and adjuvant treatment".)

Surgery for early stage invasive breast cancer With the emergence of breast conserving therapy (BCT), many women now have the option of preserving a cosmetically acceptable breast without sacrificing survival. The goals of BCT are to provide a cancer operation equivalent to mastectomy and a cosmetically acceptable breast, with a low rate of recurrence in the treated breast. All of the available data, including six randomized trials directly comparing BCT with mastectomy and an overview of completed trials [3], show equivalent survival with BCT as compared to mastectomy. Breast reconstruction has increased in popularity, largely due to changing attitudes among women with breast cancer and their doctors, and recognition of the psychosocial benefits gained by reconstruction. The type of breast surgery impacts on the need for breast reconstruction. Women undergoing BCT generally do not require reconstruction, except in cases where the specimen represents a large portion of a small breast. In contrast, the defect resulting from mastectomy requires reconstruction. (See "Mastectomy and breast conserving therapy for invasive breast cancer".) (See "Breast reconstruction in women with breast cancer".)

Radiation therapy Radiation therapy (RT) is a component of BCT and may also be indicated after mastectomy. The intent of RT delivery is to eradicate subclinical residual disease and minimize local recurrence rates. (See "Role of radiation therapy in breast conservation therapy".) (See "Postmastectomy chest wall irradiation".) (See "Techniques and complications of breast and chest wall irradiation for early stage breast cancer".)

Management of the regional lymph nodes The lymphatic drainage pathways of the breast (axillary, internal mammary, and supraclavicular nodal groups) are the regional areas most likely to be involved with metastatic breast cancer. Axillary lymph node staging and dissection have traditionally been a routine component of the management of early stage invasive breast cancer. In patients with clinically node negative breast cancer, sentinel lymph node biopsy identifies axillary node involvement, thereby obviating the need for more extensive surgery in some patients. (See "Management of the regional lymph nodes in breast cancer".) (See "Sentinel lymph node biopsy for breast cancer: Indications and outcomes".)

Adjuvant systemic therapy Adjuvant systemic therapy refers to the administration of endocrine therapy, chemotherapy, and/or biologic therapy after definitive local therapy for breast cancer. Adjuvant systemic therapy is administered following primary surgery for early breast cancer to prevent breast cancer recurrence and to improve overall survival. However, patient selection is important because not all patients receive benefit from adjuvant therapy and because it is associated with significant toxicities. Therefore, when considering adjuvant systemic therapy, it is important to estimate a patients risk for recurrence, their likelihood to benefit from adjuvant treatment, potential risks of treatment, and patient preferences. Hormone receptor status, human epidermal growth factor receptor 2 (HER2) expression, and lymph node status are important markers that indicate whether a patient should be treated with endocrine therapy, chemotherapy, and HER2-directed therapy. (See "Clinical decisions in systemic adjuvant therapy for early breast cancer".) (See "Adjuvant endocrine therapy for postmenopausal women with early stage breast cancer".) (See "Adjuvant endocrine therapy for premenopausal women with early stage breast cancer".) (See "Adjuvant chemotherapy for early stage HER2-negative breast cancer".) (See "Adjuvant chemotherapy and trastuzumab for HER2-positive early breast cancer".) (See "Adjuvant systemic therapy for older women with early stage breast cancer".)

MANAGEMENT OF LOCALLY RECURRENT DISEASE Following initial treatment for operable breast cancer, disease can recur locally, regionally, and/or at distant metastatic sites. A local recurrence is defined as reappearance of cancer on the ipsilateral chest wall or preserved breast. A regional recurrence denotes tumor involving the regional lymph nodes, usually ipsilateral axillary or supraclavicular, less commonly infraclavicular and/or internal mammary nodes. Aggressive multimodality treatment has the potential to provide long-term disease control in a substantial number of patients who develop an isolated locoregional recurrence after mastectomy or breast conserving therapy. (See "Management of locoregional recurrence of breast cancer after breast conserving therapy" and "Management of locoregional recurrence of breast cancer after mastectomy".) MANAGEMENT OF METASTATIC DISEASE Fewer than 10 percent of women present with metastatic disease at the time of diagnosis. However, the majority of women who relapse after definitive therapy for early stage or locally advanced disease will do so with disseminated metastatic disease rather than an isolated local recurrence. The most common sites of distant tumor involvement are the bones, liver, and lungs. The median survival for patients with stage IV breast cancer is 18 to 24 months, although the range extends from only a few months to many years [4,5]. The selection

of a therapeutic strategy depends upon both tumor biology and clinical factors, with the goal being a tailored approach. Although a subset of patients with oligometastatic disease may benefit from an intensified locoregional approach, most patients with metastatic breast cancer receive systemic medical therapy, consisting of chemotherapy, endocrine therapy, and/or biologic therapies, and supportive care measures. (See "Systemic treatment for metastatic breast cancer: General principles".) BREAST CANCER SURVIVORSHIP Breast cancer follow-up and surveillance, complications of therapy, and other survivorship issues are discussed in detail separately. (See "Follow-up for breast cancer survivors: Recommendations for surveillance after therapy".) (See "Follow-up for breast cancer survivors: Patterns of relapse and long-term complications of therapy".) (See "Approach to the survivor of breast cancer".)

INFORMATION FOR PATIENTS Educational materials on this topic are available for patients. (See "Patient information: Breast cancer (The Basics)" and "Patient information: Breast cancer guide to diagnosis and treatment" and "Patient information: Risk factors for breast cancer" and"Patient information: Early stage breast cancer treatment in postmenopausal women" and "Patient information: Early stage breast cancer treatment in premenopausal women" and "Patient information: Surgery for breast cancer Mastectomy and breast conserving therapy" and"Patient information: Adjuvant chemotherapy and trastuzumab (Herceptin) for early stage breast cancer" and "Patient information: Locally advanced and inflammatory breast cancer" and "Patient information: Treatment of metastatic breast cancer".) We encourage you to print or e-mail this topic review, or to refer patients to our public web site, www.uptodate.com/patients, which includes this and other topics. Use of UpToDate is subject to the Subscription and License Agreement. REFERENCES 1. Jemal A, Siegel R, Xu J, Ward E. Cancer statistics, 2010. CA Cancer J Clin 2010; 60:277. 2. Edge, SB, Byrd, DR, Compton, CC, et al (Eds). AJCC (American Joint Committee on Cancer) Cancer Staging Manual, 7th ed, Springer, New York, 2010. 3. Clarke M, Collins R, Darby S, et al. Effects of radiotherapy and of differences in the extent of surgery for early breast cancer on local recurrence and 15-year survival: an overview of the randomised trials. Lancet 2005; 366:2087. 4. Lee CG, McCormick B, Mazumdar M, et al. Infiltrating breast carcinoma in patients age 30 years and younger: long term outcome for life, relapse, and second primary tumors. Int J Radiat Oncol Biol Phys 1992; 23:969. 5. Vogel CL, Azevedo S, Hilsenbeck S, et al. Survival after first recurrence of breast cancer. The Miami experience. Cancer 1992; 70:129.