TY - JOUR
T1 - The yield of full BRCA1/2 genotyping in Israeli high-risk breast/ovarian cancer patients who do not carry the predominant mutations
AU - Barnes-Kedar, Inbal
AU - Bernstein-Molho, Rinat
AU - Ginzach, Nava
AU - Hartmajer, Shulamit
AU - Shapira, Tamar
AU - Magal, Nurit
AU - Kalis, Marina Lifshitc
AU - Peretz, Tamar
AU - Shohat, Mordechai
AU - Basel-Salmon, Lina
AU - Friedman, Eitan
AU - Bazak, Lily
AU - Goldberg, Yael
N1 - Publisher Copyright:
© 2018, Springer Science+Business Media, LLC, part of Springer Nature.
PY - 2018/11/1
Y1 - 2018/11/1
N2 - 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.
AB - 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.
KW - Ashkenazi
KW - BRCA1 BRCA2
KW - Breast cancer
KW - Founder
KW - Israel
KW - Jewish
KW - Non-founder mutations
KW - Ovarian cancer
UR - http://www.scopus.com/inward/record.url?scp=85049927355&partnerID=8YFLogxK
U2 - 10.1007/s10549-018-4887-7
DO - 10.1007/s10549-018-4887-7
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AN - SCOPUS:85049927355
SN - 0167-6806
VL - 172
SP - 151
EP - 157
JO - Breast Cancer Research and Treatment
JF - Breast Cancer Research and Treatment
IS - 1
ER -