Prevention of breast&ovarian cancer in women with BRCA-1/2 mutations - A decision-analytic evaluation

Abstract

Abstract Background Women who have inherited BRCA-1/2 mutations have substantially elevated lifetime risks for developing breast and/or ovarian cancer and may develop these cancers around age 30. Therefore, breast and ovarian cancer prevention should be administered relatively early in life for those women. We systematically evaluate the long-term effectiveness and cost-effectiveness of different breast and ovarian cancer prevention strategies in women with BRCA-1/2 mutations in Germany. Methods A decision-analytic Markov model simulating lifetime breast and ovarian cancer development in BRCA-1/2 carriers was developed to evaluate different strategies including intensified surveillance (IS), prophylactic bilateral mastectomy (PBM), and prophylactic bilateral oophorectomy (PBSO) alone or in combination at different ages. German clinical, epidemiological and cost (in 2018 Euro) data were used. Outcomes included cancer incidences, mortality, life years (LYs), quality-adjusted life years (QALYs), and discounted incremental cost-effectiveness ratios (ICER). Results All intervention strategies are more effective and less costly than IS alone. Prevention with PBM plus PBSO at age 30 maximizes life expectancy with 6.3 LYs gained, whereas PBM at age 30 with delayed PBSO at age 35 improves quality of life with 11.1 QALYs gained, when compared to IS alone. Both strategies are cost effective with ICER significantly below 10,000 EUR/LY or QALY gained. Conclusions Based on our results, PBM at age 30 plus PBSO between age 30 and 40 prolongs life and is cost effective in women with BRCA-1/2 mutations in Germany. Serial preventive surgeries with delayed PBSO potentially improve quality of life for women. We therefore suggest that efforts should be directed to carefully and thoroughly inform women with BRCA-1/2 mutations about their options to prevent breast and ovarian cancer. Key messages Prophylactic mastectomy at age 30 combined with prophylactic oophorectomy between age 30 and 40 may prolong lives and be cost effective in German women with BRCA- 1/2 mutations. Women’s quality of life might be improved by a delayed prophylactic oophorectomy after a prophylactic mastectomy.