Genetic risk in context: calculating the penetrance of BRCA1 and BRCA2 mutations. J Natl Cancer Inst 2002;94:1185–1187

With advances in genetic research, many experts anticipate an era of “personalized medicine, ” in which knowledge about genetic risk will be used to guide preventive health care, drug choices, and disease management (1–3). This approach may hold particular promise for cancer, because information about a genetic susceptibility could provide valuable opportunities to tailor cancer screening and prevention strategies and to refine clinical and behavioral interventions to reduce cancer risk. How-ever, this paradigm calls for genetic tests that provide accurate risk predictions, a goal that may be far from easy to achieve. The BRCA1 and BRCA2 genes are an important case in point. Several studies have estimated the penetrance of BRCA1 mutations, that is, the likelihood that breast or ovarian cancer will occur when a deleterious mutation is present. Nearly all conclude that cancer risk is elevated when a BRCA1 or BRCA