Personalized risk-prediction-based primary prevention is feasible assessing information on family history and BRCA1/2 (BRCA) testing. Women with either BRCA mutations or who test negative (non-BRCA) face a very high risk (∼75%) or a moderate risk (20-40%) of breast cancer and an increased risk of ovarian cancer respectively. Although prophylactic surgery and intensive surveillance are the recommended approaches to reduce the risks of cancer and mortality for BRCA and non-BRCA women respectively multiple variables complicate final preventive intervention decision. Here, I discuss how considering the latest advances and data emerging could help to choose between risk-reducing surgery (bilateral salpingo-oophorectomy and/or bilateral mastectomy) and intensive surveillance including MRI for each woman at risk. The future perspectives to explain missing heritability with current and next-generation of genome-wide association studies and thus to develop novel genetic tests for predicting risks of women who test negative for BRCA mutations are also discussed.