Brca1 and Brca2 Mutations

The Challenge

• Description: In normal cells, the BRCA1 and BRCA2 genes encode for double-strand DNA repair proteins that keep the cells from abnormally growing. Although hundreds of mutations to these genes have been identified, only a limited number are associated with an increased tumor risk. A lack of BRCA1 function seems to lead to nonfunctional X-chromosome inactivation, preferentially leading to breast and ovarian cancers. When abnormal, these genes are the most common cause of hereditary breast cancer. Breast cancers linked to these mutations occur in younger women and more often affect both breasts. Women with these inherited mutations also have an increased risk for developing ovarian (5-fold increase) and fallopian tube cancer (up to a 30-fold increase). In males, BRCA mutations can increase the risk of other cancers, such as colon, pancreatic, and prostate cancer.

• Scope of the Problem: Up to 20% of women with a family history of breast cancer have a mutation in a major gene, most often in the breast cancer susceptibility genes, BRCA1 and BRCA2. Mutations are more common in Jewish people of Ashkenazi (Eastern Europe) origin than in other racial and ethnic groups (mutation frequency approximately is 1/400 unselected patients). Women with BRCA1 mutations have a 60% lifetime risk for breast cancer, and BRCA2 mutations carry an 85% risk for breast cancer and up to 30% risk for ovarian cancer. In some families with BRCA1 mutations, the lifetime risk for breast cancer is as high as 80%. Only 5%–10% of patients with breast cancer have a family history of breast cancer.

• Objectives of Management: To identify patients for whom BRCA gene testing is warranted and to provide appropriate counseling on the basis of those test findings.