Average risks of breast and ovarian cancer associated with BRCA1 or BRCA2 mutations detected in case series unselected for family history: a combined analysis of 22 studies.

Abstract (PubMed)

Germline mutations in BRCA1 and BRCA2 confer high risks of breast and ovarian cancer, but the average magnitude of these risks is uncertain and may depend on the context in which the mutation was identified. Estimates of risk from families in which multiple individuals are affected may be biased upward due to ascertainment. We have conducted a combined analysis of 22 studies in which BRCA1 and BRCA2 mutation carriers were identified by testing individuals from various populations or from individuals with disease or known BRCA mutation carriers, but not selected on the basis of family history alone. The average cumulative risks by age 70 years of breast cancer and ovarian cancer for BRCA1 mutation carriers were 65% (95% CI 44-78%) and 39% (95% CI 18-54%), respectively, and for BRCA2 mutation carriers were 45% (95% CI 31-56%) and 11% (95% CI 2.4-19%), respectively. These estimates are substantially lower than those estimated from high-risk families, and confirm that the breast and ovarian cancer risks for BRCA1 and BRCA2 mutation carriers depend on the context in which the mutations were identified.