Genotype in BRCA-associated Breast Cancers

Women with BRCA1 or 2 mutations are at high risk for breast cancer. For BRCA1, a trend of increasing risk has been associated with increasing downstream (3′) location for mutations compared to the upstream (5′) mutations in the gene. For BRCA2, an increased risk of breast cancer has been associated with mutations outside of the ovarian cancer cluster region (OCCR). We sought to determine the mutation position in BRCA‐associated breast cancers and whether or not there was a genotype‐phenotype correlation. Breast cancer patients with BRCA1/2 mutations were identified by a search of a prospectively maintained data base. Mutation site, patient, and tumor characteristics were determined through retrospective review. One hundred and sixty‐four patients with BRCA1‐associated breast cancer and 109 patients with BRCA2‐associated breast cancer were identified. Among patients with BRCA1‐associated cancers, 86 (52%) had mutations in the 5′ half of the gene. Among patients with BRCA2‐associated breast cancers, 40 (37%) had OCCR mutations. Although BRCA1‐associated tumors were more likely to be ER/PR‐ than BRCA2‐associated cancers (p