Population-Wide Screening for Germline BRCA1/2 Mutations: Too Much of a Good Thing?

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 Germline testing for highly penetrant mutations in cancer susceptibility genes such as BRCA1 and BRCA2 (BRCA1/2) can prevent cancer and save lives. Inherited BRCA1/2 mutations confer a 39% to 85% lifetime risk of female breast cancer and an 11% to 62% lifetime risk of ovarian cancer.^1–7 Identifying BRCA1/2 mutation carriers thus allows for prophylactic surgeries, which can markedly decrease cancer incidence, morbidity, and mortality.^8–11 Despite these benefits and increasing public awareness, a low fraction (35% in a recent Israeli study)¹ of women with high-risk histories have undergone BRCA1/2 testing. Moreover, women from families with few female relatives are unlikely to recognize their risk of carrying a BRCA1/2 mutation until they themselves develop cancer. Recently, citing the impact of risk-reducing surgeries, King et al¹² published a high-profile appeal for BRCA1/2 mutation screening to be offered to all US women at age 30 years.^12–14 King is to be commended for stimulating a serious discussion on the potential impact of bringing modern genetic medicine to the general population in a compelling circumstance. However, because testing all women for BRCA1/2 mutations would represent the first population-based screening for a hereditary cancer syndrome, careful consideration of the potential limitations, risks, and benefits of population-wide BRCA1/2 testing is essential......