Modelling study of cost-effectiveness of gene-specific prevention strategies for ovarian and breast cancer

Pathogenic variants (PVs) in BRCA1, BRCA2, PALB2, RAD51C, RAD51D, and BRIP1 cancer susceptibility genes (CSGs) confer an increased risk of ovarian cancer (OC), while PVs in BRCA1, BRCA2, PALB2, RAD51C, and RAD51D also confer an elevated breast cancer (BC) risk. Risk-reducing surgery, medical prevention, and BC surveillance of the opportunity to prevent cancers and deaths, but their cost-effectiveness for individual CSGs is not clear. A decision-analytic Markov model with a simulated cohort of women aged 30 years found that undergoing both risk-reducing mastectomy (RRM) and risk-reducing salpingo-oophorectomy (RRSO) was most cost-effective, maximizing cancer prevented for individuals carrying BRCA1 (RRM at age 30 years, RRSO at age 35 years), BRCA2 (RRM at age 35 years, RRSO at age 40 years), and PALB2 (RRM at age 40 years, RRSO at age 45 years) PVs, while RRSO was cost-effective at age 45 years for women with RAD51C, RAD51D, and BRIP1 PVs. The authors conclude that these findings support personalizing risk-reducing surgery and guideline recommendations for individual CSG-specific OC and BC risk management.