The role of BRCA1 AND BRCA2 in hereditary breast cancer Review Article

BRCA1 and BRCA2 account for most cases of hereditary breast cancer in the United States and Europe. These are suppressor genes that are inherited in an autosomal dominant fashion. Several studies showed that the histologic and molecular phenotype of BRCA-associated tumors is different from that of nonhereditary tumors. There is a difference in steroid receptor status between BRCA1 and 2 tumors regard to chemoprevention of breast cancer with antiestrogenes. 93-100% of BRCA2 associated breast cancers are ER/PR. Breast cancers associated with BRCA1 mutations are frequently of a higher grade and are hormone receptor-negative in one third of them. A higher proportion of cancers related to a BRCA1 mutation have atypical or typical medullary histologic features. The lifetime cumulative risk of invasive breast cancer for individuals with BRCA1 or BRCA2 mutations ranges from 50% to 87%. Familial breast cancer, however, accounts for fewer than 10% of all breast cancers, and BRCA1-related and BRCA2-related familial disease constitutes only two-thirds to three-fourths of these cases. Among women younger than 35 years old with breast cancer, 10% to 15% have a BRCA1 mutation. Woman with BRCA 1/2 mutations already affected by the disease have a risk, to age 70, of contralateral breast cancer that ranges between 50% and 64%. It has been difficult to determine whether germline BRCA 1/2 status has an effect on breast cancer outcome and the results from several studies remain controversial. There are preliminary data that BRCA 1/2 related tumors may have a faster growth rate than sporadic tumors. In these women prophylactic mastectomy, chemoprevention with tamoxifen or prophylactic oophorectony are reasonable options. Genetic testing for BRCA 1/2 mutations should be done in those with a significant family history of breast or ovarian cancer, those with a diagnosis of breast or ovarian cancer below 50 years of age and those with a blood relative who is known to have a mutation in BRCA 1 or 2. Ongoing clinical trials will determine who the optimal subjects are for screening, how screening and counseling should be conducted and what type of societal involvement is needed so that genetic screening can be used without exposing the subject to unexpected risks and consequences.