Abstract 4271: Population-wide vs. carrier-probability-based BRCA1/2 mutation testing in the Washington Ashkenazi Study

Background: Currently, women are referred for BRCA1/2 mutation testing if their family history of breast and ovarian cancer indicates they have sufficient probability of carrying mutations. In contrast, calls have intensified for population-wide testing for BRCA1/2 founder mutations among Ashkenazi Jews, due to relatively high mutation prevalence (2.5%) and decreasing genotyping costs. However, population-wide testing would strain genetic counseling resources and incur costs from testing mostly mutation-negative women. We compared the performance of population-wide vs. carrier-probability-based BRCA1/2 testing in the community-based Washington Ashkenazi Study (WAS). Methods: BRCA1/2 carrier-probabilities based on reported family histories were calculated using BRCAPRO for 4589 probands (102 BRCA1/2 mutation-carriers) in WAS. For each carrier-probability threshold, we compared the percent of mutations found (sensitivity) vs. the percent of women requiring mutation testing, overall and by proband age. At example carrier-probability thresholds, undetected and detected carriers’ attributes were compared using nonparametric tests. Results: A 1.2% carrier-probability threshold identified 80% of BRCA1/2 mutations in the 35% of women with highest carrier-probability. For women under age 40, 94% of BRCA1/2 mutations were identified in the 50% of women with highest carrier-probability. Compared to identified mutation-carriers, missed mutation-carriers had no personal cancer history, no affected first- and second-degree relatives (p Conclusion: Carrier-probability-based BRCA1/2 mutation testing identified large majorities of mutation-carriers and would have avoided testing for many mutation-negative women. Missed mutation-carriers were older and cancer-free and would gain minimal benefit from risk-reducing interventions. A cost-effective carrier-probability threshold could acceptably tradeoff identifying BRCA1/2 mutation carriers before they get cancer while testing as few women as possible. Citation Format: Ana F. Best, Margaret A. Tucker, Hormuzd A. Katki. Population-wide vs. carrier-probability-based BRCA1/2 mutation testing in the Washington Ashkenazi Study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4271. doi:10.1158/1538-7445.AM2017-4271