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Breast Cancer Res Treat. 2018 Nov;172(1):151-157. doi: 10.1007/s10549-018-4887-7. Epub 2018 Jul 16.

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

Author information

1
Recanati Genetics Institute, Beilinson Hospital, Rabin Medical Center, Petach Tikva, Israel.
2
Breast Cancer Center, Oncology Institute, Chaim Sheba Medical Center, Tel-Hashomer, Israel.
3
Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
4
Medical Genetics Institute, Meir Medical Center, Kfar Sava, Israel.
5
Maccabi Health Services, Rehovot, Israel.
6
Sharett Institute of Oncology, Hebrew University-Hadassah Medical Center, Jerusalem, Israel.
7
Susanne Levy Gertner Oncogenetics Unit, The Danek Gertner Institute of Human Genetics, Chaim Sheba Medical Center, Tel-Hashomer, Israel.
8
Recanati Genetics Institute, Beilinson Hospital, Rabin Medical Center, Petach Tikva, Israel. yaelgo43@gmail.com.
9
Maccabi Health Services, Rehovot, Israel. yaelgo43@gmail.com.

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.

KEYWORDS:

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

PMID:
30014164
DOI:
10.1007/s10549-018-4887-7
[Indexed for MEDLINE]

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