Less than 1% of breast cancers occur in women younger than 25 years of age. After age 30, there is a sharp increase in the incidence of breast cancer. Except for a short plateau between the ages of 45 and 50 years, the incidence increases steadily with age (2).
Family History Of women who develop breast cancer, 20% to 30% have a family history of the disease. Although any family history of breast cancer increases the overall relative risk, this risk is not significantly increased if the disease was diagnosed postmenopausally in a first-degree or more distant relative (3). If a woman’s mother or sister had unilateral breast cancer premenopausally, her lifetime risk of developing the disease approaches 30%, whereas a woman whose mother or sister had bilateral breast cancers premenopausally has at least a 40% to 50% lifetime risk. The increased incidence in these women is probably the result of inherited oncogenes.
Approximately 5% to 10% of breast cancers have an inherited basis. All inherited genes are autosomal dominant but have variable penetrance. Men carry the gene 50% of the time. The most common mutations are the BRCA1 (chromosome 17q21) and BRCA2 (chromosome 13q12-13) gene deletions. Carriers of these germline mutations have up to a 4% per year risk of developing breast cancer and a lifetime risk that ranges from 35% to 85% (4). These individuals have up to a 65% risk of developing a contralateral breast cancer. The BRCA1 mutation is associated with an increased risk of ovarian and prostate cancer, whereas BRCA2 carriers, although less common, demonstrate increased risks of male breast and prostate cancers. Both mutations are rare in the general public (0.1%) but are more commonly identified in Jews of Ashkenazi descent (1% to 2.3%) (5). Genetic testing is available and should be considered if there is a high likelihood that results will be positive and will be used to inﬂuence decisions regarding the clinical management of the care of the patient and her family. Patients with three of more relatives with breast or ovarian cancer with one of the relatives being diagnosed before the age of 50, two first-or second-degree relatives with breast or ovarian cancer, any relative with male breast cancer, patients whose cancer has been diagnosed before the age of 50, and any patients with both breast and ovarian cancer in their family should undergo genetic counseling for BRCA testing. Ashkenazi Jewish patients should undergo genetic counseling if any first-degree relative, or two second-degree relatives on the same side have breast or ovarian cancer (6). Genetic testing is increasingly important given the evidence that prophylactic surgery may prevent new cancers from occurring, as well as prolong survival, in some cases. A prospective multicenter cohort study of 2,482 women with BRCA1 and BRCA2 mutations between 1974 and 2008 showed risk-reducing mastectomy was associated with a decreased risk of breast cancer. Risk-reducing salpingooophorectomy was associated with decreased risk of ovarian cancer, first diagnosis of breast cancer, all-cause mortality, breast cancer–specific mortality, and ovarian cancer–specific mortality (7).
Diet, Obesity, and Alcohol
There are marked geographic differences in the incidence of breast cancer that may be related to diet. A meta-analysis demonstrated an association between a healthy diet and lower risk of breast cancer (8). Although a definitive relationship between total alcohol consumption and increased risk of breast cancer has yet to be determined, high wine intake was associated with elevated risk (8,9).
The risk of breast cancer increases with the length of a woman’s reproductive phase (10). Although early menarche was reported among breast cancer patients, early menopause appears to protect against the development of the disease, with artificial menopause from oophorectomy lowering the risk more than early natural menopause (11). There is no clear association between the risk of breast cancer and menstrual irregularity or the duration of menses.