The BRCA1 and BRCA2 gene mutations, on chromosome 17 and 13, respectively, account for the majority of autosomal dominant inherited breast cancers.
Both genes are believed to be tumor suppressor genes whose products are involved with maintaining DNA integrity and transcriptional regulation.
Mutation rates may vary by ethnic and racial groups.
- For BRCA1 mutations, the highest rates occur among Ashkenazi Jewish women (8.3%)
- followed by Hispanic women (3.5%),
- non-Hispanic white women (2.2%),
- African American women (1.3%), and
- Asian American women (0.5%).
Women who inherit a mutation in the BRCA1 or BRCA2 gene have an estimated 50-80% lifetime risk of developing breast cancer.
Specifically, BRCA1 mutations are seen in 7% of families with multiple breast cancers and 40% of families with breast and ovarian cancer.
BRCA1 mutation carries a lifetime risk of 40% for developing ovarian cancer and are also at a higher risk of colon cancer and prostate cancer.
Breast cancer that develops in BRCA1 mutation carriers are more likely to be high-grade, and ER, PR, and HER-2/neu negative (triple negative) or basal-like subtype.
BRCA2 mutations are identified in 10-20% of families at high risk for breast and ovarian cancers and in only 2.7% of women with early-onset breast cancer.
Women with a BRCA2 mutation have approximately 10% lifetime risk of ovarian cancer.
BRCA2 mutation carriers who develop breast cancer are more likely to have a high grade, ER+/PR+, and HER-2/neu negative cancer (luminal type).
BRCA2 is also a risk factor for male breast cancer.
Other cancers associated with BRCA2 mutations include prostate, pancreatic, fallopian tube, bladder, non-Hodgkin lymphoma, and basal cell carcinoma.