Refining BRCA1 and BRCA2 penetrance estimates in the clinic

Genetic testing for mutations in BRCA1 and BRCA2 can provide important information to women and help guide clinical management decisions regarding interventions such as oophorectomy to reduce cancer risk. However, variability exists in risks of breast and ovarian cancer in individual BRCA1 and BRCA2 mutation carriers, with potential contributing factors including genotype-phenotype correlations, modifier genes, environmental and reproductive exposures, and the impact of interventions. Ultimately, the clinical goal is to provide individualized assessment of breast and ovarian cancer risk to BRCA1 and BRCA2 mutation carriers accounting for these variables to aid decision-making. This article discusses factors affecting the penetrance of cancer risks in BRCA1/2 mutation carriers.