Real World Cost-Effectiveness Analysis of Population Screening for BRCA Variants among Ashkenazi Jews Compared with Family History-Based Strategies

SIMPLE SUMMARY: Identifying BRCA mutations carriers reduces cancer incidence by surveillance and prevention. We analyzed the cost-effectiveness of population screening (PS) for BRCA mutations in Ashkenazi Jews (AJ), for whom carrier rate is 2.5%, compared with existing strategies: cascade testing (CT) in carrier’s relatives, and international family history (IFH)-based guidelines. We estimated quality-adjusted life-years (QALYs) gained, and cost-effectiveness for PS vs. existing strategies. Per 1000 women, PS vs. CT predicted 21.6 QALYs gained, and lifetime decrease of three breast cancer (BC) and four ovarian cancer (OC) cases, and PS vs. IFH predicted 6.3 QALYs gained, decrease of 1 BC and 1 OC. PS was less costly than CT (−3097 USD/QALY), and more costly than IFH (+42,261 USD/QALY), yet still cost-effective, and the most effective screening strategy for cancer prevention. The alternative strategies restrict the number of carriers identified, precluding cancer prevention in unidentified carriers. Population BRCA testing should be available to all AJ women. ABSTRACT: Identifying carriers of pathogenic BRCA1/BRCA2 variants reduces cancer morbidity and mortality through surveillance and prevention. We analyzed the cost-effectiveness of BRCA1/BRCA2 population screening (PS) in Ashkenazi Jews (AJ), for whom carrier rate is 2.5%, compared with two existing strategies: cascade testing (CT) in carrier’s relatives (≥25% carrier probability) and international family history (IFH)-based guidelines (>10% probability). We used a decision analytic-model to estimate quality-adjusted life-years (QALY) gained, and incremental cost-effectiveness ratio for PS vs. alternative strategies. Analysis was conducted from payer-perspective, based on actual costs. Per 1000 women, the model predicted 21.6 QALYs gained, a lifetime decrease of three breast cancer (BC) and four ovarian cancer (OC) cases for PS vs. CT, and 6.3 QALYs gained, a lifetime decrease of 1 BC and 1 OC cases comparing PS vs. IFH. PS was less costly compared with CT (−3097 USD/QALY), and more costly than IFH (+42,261 USD/QALY), yet still cost-effective, from a public health policy perspective. Our results are robust to sensitivity analysis; PS was the most effective strategy in all analyses. PS is highly cost-effective, and the most effective screening strategy for breast and ovarian cancer prevention. BRCA testing should be available to all AJ women, irrespective of family history.