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

Population based BRCA1/BRCA2 testing has been found to be cost-effective compared to family-history based testing in Ashkenazi-Jewish (AJ) women >30years with four AJ-grandparents. However, individuals may have one, two or three AJ 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 one, two and three AJ grandparents.

Life time costs and effects of population and family-history based testing were compared using a decision analysis model. 56% BRCA carriers are missed by family-history criteria alone. Analyses are conducted for UK and USA populations. Model parameters are obtained from the GCaPPS trial and published literature. Model parameters and BRCA population prevalence for individuals with three, two or one AJ grandparents are adjusted for the relative frequency of BRCA mutations in the AJ and general populations. Incremental cost-effectiveness ratios were calculated for all AJ-grandparent scenarios. Costs along with outcomes discounted at 3.5%. The time horizon of the analysis is 'life-time' and perspective is 'payer'. Probabilistic sensitivity-analysis (PSA) evaluated model uncertainty.

Population testing for BRCA mutations is cost saving in AJ women with two, three or four grandparents (22-33 days life-gained) in UK and one, two, three or four grandparents (12-26 days life-gained) in USA populations respectively. It is also extremely cost-effective in UK women with just one AJ-grandparent with an incremental-cost-effectiveness-ratio (ICER)= £863/QALY and 15days life-gained. Results show that population-testing remains cost-effective at the £20,000-30000/QALY and $100,000/QALY willingness-to-pay thresholds for all four AJ-grandparent scenarios with ≥95% simulations found to be cost-effective on PSA. Population-testing remains cost-effective in the absence of reduction in breast cancer risk from oophorectomy and at lower RRM (13%)/RRSO (20%) rates.

Population-testing for BRCA mutations is cost-effective in the UK and USA with varying levels of AJ ancestry. These results support population testing in AJ women with 1-4 AJ-grandparent ancestry.