Prevention and Management of Hereditary Breast Cancer

It has been 10 years since the BRCA1 gene was first identified. During this decade, genetic testing for breast cancer susceptibility has been incorporated into the practice of oncology. In this process, the identification of families at the highest hereditary risk for cancer has served as a model to test strategies for prevention or early detection of breast malignancies. An emerging literature has explored primary prevention through risk reducing surgery and chemoprevention, as well as secondary prevention utilizing such approaches as magnetic resonance imaging (MRI) to achieve early detection of breast cancer in women with BRCA1 or BRCA2 mutations. Tailored treatments are being explored for newly diagnosed women with BRCA mutations. Ultimately, individual risk estimates and clinical management plans will be generated for women carrying BRCA mutations, based on consideration of the particular mutation inherited and also on the presence of modifying genetic and environmental factors. Both BRCA1 and BRCA2 are involved in the cellular response to DNA damage and interact with other proteins involved in double-stranded DNA repair. The effects of inherited mutations in these genes are similar, and mutations of both types predispose carriers to female and male breast cancer, and to ovarian cancer. The risk of male breast cancer is higher in BRCA2 carriers; ovarian cancer risk is higher in those carrying BRCA1 mutations. In addition, BRCA2 mutations appear to predispose both men and women to a wide range of other cancer types. The reasons for these tissue-specific differences between the two genes is not clear.