Presymptomatic DNA testing and prophylactic surgery in families with a BRCA1 or BRCA2 mutation

Background Germline mutations in the BRCA1. and BRCA2 genes highly predispo se to breast and ovarian cancer. In families with BRCA1 or BRCA2 mutations, identification of mutation carriers is clinically relevant in view of the options for surveillance and prevention. Methods We assessed presymptomatic DNA testing and prophylactic surgery in 53 consecutive families presenting to the Rotterdam Family Cancer Clinic wi th a known BRCA1 or BRCA2 mutation. We identified predictors for DNA testin g and prophylactic surgery with univariate and multivariate analysis. Findings 682 unaffected individuals with a 50% risk (275 women and 271 men) or with a 25% risk (136 women) for carrying a mutation were identified and offered a DNA test. Presymptomatic DNA testing was requested by 48% (198 o f 411) of women and 22% (59 of 271) of men (odds ratio for difference betwe en sexes 3.21 [95% CI 2.27-4.51]; p<0.001). In women, DNA testing was signi ficantly more frequent at young age, in the presence of children, and at hi gh pre-test genetic risk for a mutation. Of the unaffected women with an id entified mutation who were eligible for prophylactic surgery, 51% (35 of 68 ) opted for bilateral mastectomy and 64% (29 of 45) for oophorectomy. Paren thood was a predictor for prophylactic mastectomy but not for prophylactic oophorectomy. Age was significantly associated with prophylactic oophorecto my, but not with prophylactic mastectomy, although there was a tendency tow ards mastectomy at younger ages. Interpretation In a clinical setting, we show a high demand for BRCA1 and B RCA2 testing by unaffected women at risk, and of prophylactic surgery by un affected women with the mutation. Young women with children especially opt for DNA testing and prophylactic mastectomy.