Functional implications of BRCA1 for early detection, prevention, and treatment of breast cancer

The tumor suppressor gene BRCA1 was positionally cloned in 1994. During the last 12 years, several lines of evidence have implicated BRCA1 in the maintenance of genome integrity, regulation of transcriptionn, and chromatin remodeling, suggesting that it has multiple biological roles. Germline mutations in BRCA1 confer a 56%-80% lifetime risk for breast cancer and a 15%-60% lifetime risk for ovarian cancer in women. And preliminary evidence suggests that BRCA1-linked breast and ovarian tumors behave differently from sporadic tumors, justifying a tailored approach to these cancers. Although several gaps still remain in our knowledge, it is possible to use information from basic research to illuminate clinical decisions and improve the prospects of mutation carriers. Along similar lines, genetic data derived from the clinical setting are also instrumental in determining which biochemical functions of BRCA1 contribute to its tumor suppressor actions. In this article, we explore the functional implications of BRCA1 for genetic testing (early detection), prevention, and therapy.