Cost-effectiveness of population based BRCA testing with varying Ashkenazi Jewish ancestry

BACKGROUND: Population-based BRCA1/BRCA2 testing has been found to be cost-effective compared with family history-based testing in Ashkenazi-Jewish women were > 30 years old with 4 Ashkenazi-Jewish grandparents. However, individuals may have 1, 2, or 3 Ashkenazi-Jewish grandparents, and cost-effectiveness data are lacking at these lower BRCA prevalence estimates. We present an updated cost-effectiveness analysis of population BRCA1/BRCA2 testing for women with 1, 2, and 3 Ashkenazi-Jewish grandparents. STUDY DESIGN: Decision analysis model. METHODS: Lifetime costs and effects of population and family history-based testing were compared with the use of a decision analysis model. 56% BRCA carriers are missed by family history criteria alone. Analyses were conducted for United Kingdom and United States populations. Model parameters were obtained from the Genetic Cancer Prediction through Population Screening trial and published literature. Model parameters and BRCA population prevalence for individuals with 3, 2, or 1 Ashkenazi-Jewish grandparent were adjusted for the relative frequency of BRCA mutations in the Ashkenazi-Jewish and general populations. Incremental cost-effectiveness ratios were calculated for all Ashkenazi-Jewish grandparent scenarios. Costs, along with outcomes, were discounted at 3.5%. The time horizon of the analysis is "life-time," and perspective is "payer." Probabilistic sensitivity analysis evaluated model uncertainty. RESULTS: Population testing for BRCA mutations is cost-saving in Ashkenazi-Jewish women with 2, 3, or 4 grandparents (22-33 days life-gained) in the United Kingdom and 1, 2, 3, or 4 grandparents (12-26 days life-gained) in the United States populations, respectively. It is also extremely cost-effective in women in the United Kingdom with just 1 Ashkenazi-Jewish grandparent with an incremental cost-effectiveness ratio of 863 pound per quality-adjusted life-years and 15 days life gained. Results show that population-testing remains cost-effective at the 20,000-30000 pound per quality-adjusted life-years and $100,000 per quality-adjusted life-years willingness-to-pay thresholds for all 4 Ashkenazi-Jewish grandparent scenarios, with >= 95% simulations found to be cost-effective on probabilistic sensitivity analysis. Population-testing remains cost-effective in the absence of reduction in breast cancer risk from oophorectomy and at lower risk-reducing mastectomy (13%) or risk-reducing salpingo-oophorectomy (20%) rates. CONCLUSION: Population testing for BRCA mutations with varying levels of Ashkenazi-Jewish ancestry is cost-effective in the United Kingdom and the United States. These results support population testing in Ashkenazi-Jewish women with 1-4 Ashkenazi-Jewish grandparent ancestry.