Msk of breast and ovarian cancer in women with strong family histories

Assessing the risk of breast and ovarian cancer starts with obtaining a com plete and accurate family history. This can reveal evidence of inherited ca ncer risk. The highest risk of cancer is associated with germ-line abnormal ities in several genes, including BRCA1, BRCA2, and TP53. Moderate-risk gen es associated with syndromes that are inherited in an autosomal dominant pa ttern (such as Cowden's disease, hereditary nonpolyposis colorectal cancer, Muir-Torre syndrome, and Peutz-Jeghers syndrome) exhibit lower penetrance and thus less risk of breast and/or ovarian cancer. Low-risk genes likely r equire significant environmental exposure, and although they are associated with the lowest risk of cancer, they account for more cancer than high- an d moderate-risk genes. Lifetime risks for breast or ovarian cancer can be e stimated. The Gail and Claus models, the more widely utilized models for ca lculation of lifetime breast cancer risk, are discussed. Models are also av ailable for determining the likelihood of finding a BRCA1/2 mutation (the B RCAPRO and Myriad models). Appropriate candidates for testing include affec ted individuals who are most likely to have a hereditary form of cancer. Te sting should proceed only after a thorough discussion of the risks, benefit s, and limitations of testing. Risk-reducing options are available to women with a strong family history of breast and ovarian cancer. These options i nclude high-risk screening, chemoprevention, and prophylactic surgery.