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

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Manchanda, R 
Patel, S 
Antoniou, AC 
Levy-Lahad, E 
Turnbull, C 


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. 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. STUDY DESIGN: 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 per quality-adjusted life-years and 15 days life gained. Results show that population-testing remains cost-effective at the £20,000-30000 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%) per 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.



ancestry, Ashkenazi Jewish, BRCA, cost-effectiveness, population testing

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American Journal of Obstetrics and Gynecology

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Cancer Research UK (via University of Manchester) (CRUK Ref: C1005/A12677)
Cancer Research UK (20861)
Supported by “The Eve Appeal” charity, which had no role in the study design, data collection, analysis, interpretation, writing of the report, or decision to submit for publication. The research team was independent of funders. I.J. and U.M. have a financial interest in Abcodia, Ltd, which is a company formed to develop academic and commercial development of biomarkers for screening and risk prediction; I.J. is a member of the board of Abcodia Ltd and a Director of Women’s Health Specialists Ltd. R.M. declares funding for research from Cancer Research UK and Barts and the London Charity outside this submitted work and an honorarium for grant review from Israel National institute for Health Policy Research. The other authors declare no conflict of interest.