The yield of full BRCA1 / 2 genotyping in Israeli high-risk breast/ovarian cancer patients who do not carry the predominant mutations

Purpose BRCA1 and BRCA2 genotyping results have clinical implications for cancer risk assessment and targeted therapy. Current practice in Israel is to genotype for the predominant BRCA1 / 2 mutations first, followed by full gene analysis in eligible mutation-negative individuals. This work assessed the rate of non-predominant mutations in BRCA1 / 2 in ethnically diverse high-risk cases. Methods Breast and/or ovarian cancer patients who tested negative for the predominant BRCA1 / 2 mutations were referred for comprehensive BRCA1 / 2 genotyping if calculated risk for carrying a BRCA mutation was ≥ 10%. Results Of 1258 eligible patients, 41 (3.3%) carried one of 38 mutations: 3% of Ashkenazi Jews and 3.4% of mixed ethnicities. Detection rate was < 5% among patients diagnosed with cancer younger than 40 or with bilateral breast cancer, and was 5.5% of ovarian cancer patients. Three of the carriers (7.3%) carried gene rearrangements. Three mutations were reported in more than one case. Conclusions The overall yield of comprehensive BRCA1 / 2 testing in ethnically diverse high-risk Israeli individuals is 3.3%. This is lower than expected by probability models. A slightly higher rate of BRCA1 / 2 carriers was seen among ovarian cancer cases. These data should guide BRCA1 / 2 optimal testing strategy in Israel.