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

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.

Does a proactive procedure lead to a higher uptake of predictive testing in families with a pathogenic BRCA1/BRCA2 variant? A family cancer clinic evaluation

“…Some experience with population screening for BRCA1/BRCA2 PGVs has been gained in the Ashkenazi Jewish population. Due to founder variants, this population has a 2.5% prevalence of PGVs in these genes, much higher than in most non-Ashkenazi population groups (Michaelson-Cohen et al, 2022). Nevertheless, restrictions on broad population screening mean that it is unlikely that this approach will become an alternative for cascade screening in the near future.…”

Ultrasound-identified ovarian cysts: a guide to interpretation, management, and follow-up

“…The US Preventive Services Task Force has also recommended against screening for ovarian cancer in asymptomatic women but stressed that this only applies for asymptomatic women and women who do not have risk factors for hereditary cancer syndromes 17 . In contrast, ultrasound surveillance for women with BRCA mutations before they are ready for risk-reducing surgery has been reported as a cost-effective surveillance system 18 …”

“…17 In contrast, ultrasound surveillance for women with BRCA mutations before they are ready for risk-reducing surgery has been reported as a cost-effective surveillance system. 18 Despite new guidelines against screening for ovarian cancer in an asymptomatic and low-risk general population, ultrasound imaging will be ordered for many reasons including pain, vaginal bleeding, and physical examination findings. When an adnexal cyst or mass is identified, clinicians must decide whether further testing, surgical intervention, or just close follow-up is the appropriate pathway.…”