Cancer of the Breast
Summary of Key Points
Incidence and Epidemiology
• Breast cancer is the most frequently diagnosed cancer in women in the United States, accounting for an estimated 226,870 new cases (163,570 invasive cancers and 63,300 in situ carcinomas) and 39,510 deaths in 2012.
• In the United States, the age-specific incidence of breast cancer increases with age, to a lifetime risk of breast cancer of 1 in 8 (to 110 years of age); by age 40 years, approximately 1 in 203 women will have been diagnosed with breast cancer annually; at 60 years of age, the figure is 1 in 28 women.
• Incidence rates rose 21% from 1973 to 1990, but then began to decline; mortality rates stayed relatively constant until recently, when annual decreases were seen.
• A sharp decline in the incidence of breast cancer in the early 2000s followed a decrease in the use of postmenopausal hormone replacement therapy.
• Age, family history, and both endogenous and exogenous ovarian hormone exposure have an important effect on risk and have been incorporated into models that predict individual risk of breast cancer; diet, alcohol use, and other factors play a smaller role.
• Inherited mutations in BRCA1, BRCA2, PTEN, and TP53 play a role in the development of breast cancer and can be directly tested in individuals.
Biology and Estimation of Risk
• The expression of nuclear estrogen and progesterone receptors plays an important role in the differentiation and growth of normal breast epithelium and the response of breast cancer cells to hormonal therapeutics.
• ERBB2 (human epidermal growth factor receptor 2 [HER2]) is a growth-signaling molecule on the surface of normal breast cells that is overexpressed in approximately 20% of breast cancer tumors, contributing to growth autonomy and genomic instability.
• Molecular analyses have defined at least four biological subtypes of breast cancer, including the basal type, two luminal types (so-called luminal-A and luminal-B), and the HER2-positive type.
• BRCA1 and BRCA2 are tumor suppressor genes that play a critical role in the cellular response to DNA damage; inherited mutations in these genes are associated with an increased risk of breast cancer.
• Regardless of the criteria used by an individual physician and patient to define high risk, four possible actions may be taken, some of which can be used simultaneously: (a) enhanced surveillance, (b) behavioral modification, (c) chemopreventive strategies, and (d) prophylactic mastectomy or oophorectomy.
Screening and Diagnosis
• Screening guidelines currently differ between organizations. The 2009 United States Preventive Service Task Force breast cancer screening guideline recommends biennial screening mammography for women ages 50 to 74 years and an individualized (rather than standardized) approach for women ages 40 to 49 years. The American Cancer Society continues to recommend yearly mammogram starting at age 40 years. The American Cancer Society also recommends that breast magnetic resonance imaging (MRI) be used in addition to mammographic screening in women with a lifetime risk of breast cancer greater than 20%.
• Microcalcification and soft-tissue density are the major indications for biopsy in mammographic screening; the mammographic abnormality with the highest rate of malignancy is a mass density with associated calcification.
• For patients with breast symptoms or palpable abnormalities, mammography characterizes the suspicious area, evaluates the remainder of the breast for occult lesions, and assesses the contralateral breast.
• Malignant breast masses classically are nontender and firm, with irregular borders.
• Diagnostic methods include fine-needle aspiration cytology, needle-core biopsy with ultrasound or stereotactic guidance, and excisional biopsy, with or without wire or tack localization.
Management of Noninvasive Disease
• Lobular carcinoma in situ (LCIS) is a nonpalpable lesion that usually is discovered with another indicator for biopsy; it is more common in premenopausal women and accounts for 30% to 50% of cases of carcinoma in situ.
• LCIS has a propensity for multicentricity and bilaterality; it is an indicator of risk of subsequent invasive breast cancer. The rare pleomorphic variant of LCIS seems to have a more aggressive behavior and is considered more as a precursor of invasive lobular cancer rather than a marker of breast cancer risk. Some groups advocate complete excision with free margins.
• Management of LCIS has shifted toward observation after biopsy rather than mastectomy; increasing evidence shows that tamoxifen should be considered as a preventive approach.
• The multifocal nature of LCIS makes margin clearance an unrealistic and unnecessary goal.
