A commentary on population genetic testing for primary prevention: changing landscape and the need to change paradigm

Background
BRCA1/BRCA2 genes were discovered in the early 1990s and clinical testing for these has been available since the mid-1990s. The National Institute of Health and Care Excellence and other international guidelines recommend genetic testing at a ~10% probability threshold of carrying a BRCA mutation. A detailed three-generation family history (FH) of cancer is used within complex mathematical models (e.g. BOADICEA, BRCAPRO, Manchester Scoring System) or through standardised clinical criteria to identify individuals who fulfil this probability threshold and can be offered genetic testing. Identification of unaffected carriers is important given the high risk of cancer in these women and the effective options available for clinical management, which can reduce cancer risk, improve outcomes and minimise burden of disease. Risk-reducing salpingo-oophorectomy once the family is complete is the most effective option to reduce ovarian cancer (OC) risk. Taking the combined contraceptive-pill can reduce OC-risk by half. Risk-reducing mastectomy is the most effective option for reducing breast cancer (BC) risk. Additionally, high-risk women can opt for chemoprevention with selective estrogen-receptor modulators as well as early-onset annual magnetic resonance imaging/mammography screening. Carrier identification also offers the opportunity for making informed reproductive and contraceptive choices affecting cancer risk, including timing of having children, pill-use and pre-implantation genetic diagnosis. In women affected by cancer, it offers the choice of targeted therapy using drugs like poly-ADP ribose polymerase inhibitors to improve survival as well as access to novel clinical trials. Additionally, unaffected family members can be identified through cascade testing and offered options of screening/prevention