Targeted genotyping for recurring variants in cancer susceptibility genes in non‐Ashkenazi Jewish patients with breast cancer diagnosed ≥50 years

Targeted genotyping for recurring variants in cancer susceptibility genes in non‐Ashkenazi Jewish patients with breast cancer diagnosed ≥50 years

Purpose Several recurring pathogenic variants (PVs) in BRCA1/BRCA2 and additional cancer susceptibility genes are described in the ethnically diverse Israeli population. Since 2019, testing for these recurring PVs is reimbursed unselectively for all patients with breast cancer (BC) in Israel. The ai...

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Bibliographic Details
Published in:Cancer Vol. 130; no. 16; pp. 2763 - 2769
Main Authors: Bernstein‐Molho, Rinat, Shhada, Narmeen Abu, Laitman, Yael, Netzer, Iris, Shoval, Shelley, Friedman, Eitan
Format: Journal Article
Language:English
Published: United States Wiley Subscription Services, Inc 15-08-2024
Subjects:
Adenomatous polyposis coli
Age
BRCA1 BRCA2
BRCA1 protein
BRCA2 protein
Breast cancer
cancer susceptibility genes
Diagnosis
Genes
Genotyping
Health care facilities
non‐Ashkenazi Jewish
Patients
Photovoltaic cells
recurring pathogenic variants
non‐Ashkenazi Jewish
BRCA1 BRCA2
breast cancer
cancer susceptibility genes
recurring pathogenic variants
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Summary:Purpose Several recurring pathogenic variants (PVs) in BRCA1/BRCA2 and additional cancer susceptibility genes are described in the ethnically diverse Israeli population. Since 2019, testing for these recurring PVs is reimbursed unselectively for all patients with breast cancer (BC) in Israel. The aim was to evaluate the yield of genotyping for these PVs in non‐Ashkenazi Jewish (AJ) patients with BC diagnosed ≥age 50 years. Methods Clinical and genotyping data of all patients with BC undergoing oncogenetic counseling at the Oncology Institute at Sheba Medical Center from June 2017 to December 2023 were reviewed. Results Of 2706 patients with BC (mean age at diagnosis, 54 years; range, 20–92 years) counseled, 515 patients of non‐AJ (all four grandparents) descent, diagnosed ≥age 50 years of age were genotyped, 55 with triple‐negative BC (TNBC) and 460 with non‐TNBC. One of the recurring PVs in BRCA1/BRCA2 were detected in 12.7% (7/55) of TNBC patients and 0.65% (3/460) of non‐TNBC. One patient with non‐TNBC had PMS2 PV. Low‐penetrance variants were found in 2.5% of genotyped TNBC and in 3.7% of patients with non‐TNBC, including CHEK2 c.499G>A (n = 3), APC c.3920T > A (n = 4), and heterozygous MUTYH c.1187G>A (n = 5). Following first‐pass genotyping, 146 patients performed multigene panel testing, none carried a BRCA1/BRCA2 PV, and only 5/127 non‐TNBC (3.9%) harbored PVs in CHEK2 (n = 2, c.846+1G>C and c.592+3A>T), ATM c.103C>T (n = 2), and NBN c.966C>G (n = 1). Conclusions The observed low rates of PV detection in non‐AJ non‐TNBC cases ≥age 50 years at diagnosis, mostly for clinically insignificant variants, questions the justification of unselected genotyping in this subset of patients. The rate of clinically significant pathogenic variant detection in non‐Ashkenazi Jewish patients with non–triple‐negative breast cancer older than 50 years at diagnosis is very low (0.65%). These findings question the justification of unselected genotyping in this subset of patients.
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ISSN:0008-543X
1097-0142
1097-0142
DOI:10.1002/cncr.35329