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01-11-2018 | Epidemiology

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

Authors: Inbal Barnes-Kedar, Rinat Bernstein-Molho, Nava Ginzach, Shulamit Hartmajer, Tamar Shapira, Nurit Magal, Marina Lifshitc Kalis, Tamar Peretz, Mordechai Shohat, Lina Basel-Salmon, Eitan Friedman, Lily Bazak, Yael Goldberg

Published in: Breast Cancer Research and Treatment | Issue 1/2018

Abstract

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.

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Title: The yield of full BRCA1/2 genotyping in Israeli high-risk breast/ovarian cancer patients who do not carry the predominant mutations
Authors: Inbal Barnes-Kedar
Rinat Bernstein-Molho
Nava Ginzach
Shulamit Hartmajer
Tamar Shapira
Nurit Magal
Marina Lifshitc Kalis
Tamar Peretz
Mordechai Shohat
Lina Basel-Salmon
Eitan Friedman
Lily Bazak
Yael Goldberg
Publication date: 01-11-2018
Publisher: Springer US
Published in: Breast Cancer Research and Treatment / Issue 1/2018
Print ISSN: 0167-6806
Electronic ISSN: 1573-7217
DOI: https://doi.org/10.1007/s10549-018-4887-7

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