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

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

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)151-157
Number of pages7
JournalBreast Cancer Research and Treatment
Volume172
Issue number1
DOIs
StatePublished - 1 Nov 2018

Keywords

  • Ashkenazi
  • BRCA1 BRCA2
  • Breast cancer
  • Founder
  • Israel
  • Jewish
  • Non-founder mutations
  • Ovarian cancer

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