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

  • Epidemiology
  • Published:
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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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Funding

This study was not funded by any grant.

Author information

Author notes

  1. Inbal Barnes-Kedar and Rinat Bernstein-Molho contributed equally to this work.

Authors and Affiliations

  1. Recanati Genetics Institute, Beilinson Hospital, Rabin Medical Center, Petach Tikva, Israel

    Inbal Barnes-Kedar, Nava Ginzach, Nurit Magal, Marina Lifshitc Kalis, Lina Basel-Salmon, Lily Bazak & Yael Goldberg

  2. Breast Cancer Center, Oncology Institute, Chaim Sheba Medical Center, Tel-Hashomer, Israel

    Rinat Bernstein-Molho

  3. Medical Genetics Institute, Meir Medical Center, Kfar Sava, Israel

    Shulamit Hartmajer

  4. Maccabi Health Services, Rehovot, Israel

    Tamar Shapira, Mordechai Shohat & Yael Goldberg

  5. Sharett Institute of Oncology, Hebrew University-Hadassah Medical Center, Jerusalem, Israel

    Tamar Peretz

  6. Susanne Levy Gertner Oncogenetics Unit, The Danek Gertner Institute of Human Genetics, Chaim Sheba Medical Center, Tel-Hashomer, Israel

    Lina Basel-Salmon & Eitan Friedman

  7. Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel

    Rinat Bernstein-Molho & Eitan Friedman

Authors
  1. Inbal Barnes-Kedar
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  2. Rinat Bernstein-Molho
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  3. Nava Ginzach
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  4. Shulamit Hartmajer
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  7. Marina Lifshitc Kalis
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  9. Mordechai Shohat
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  10. Lina Basel-Salmon
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  11. Eitan Friedman
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  12. Lily Bazak
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  13. Yael Goldberg
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Corresponding author

Correspondence to Yael Goldberg.

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Conflict of interest

All authors declare no conflict of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. The study was approved by the IRB in the participating institutions. As data were aggregative and anonymous, no informed consent was required by the institutional IRB.

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Barnes-Kedar, I., Bernstein-Molho, R., Ginzach, N. et al. The yield of full BRCA1/2 genotyping in Israeli high-risk breast/ovarian cancer patients who do not carry the predominant mutations. Breast Cancer Res Treat 172, 151–157 (2018). https://doi.org/10.1007/s10549-018-4887-7

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  • DOI: https://doi.org/10.1007/s10549-018-4887-7

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