Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2024 Aug 15;130(16):2763-2769.
doi: 10.1002/cncr.35329. Epub 2024 Apr 17.

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

Rinat Bernstein-Molho  1   2 , Narmeen Abu Shhada  3 , Yael Laitman  1 , Iris Netzer  1 , Shelley Shoval  1 , Eitan Friedman  2   4
Affiliations
Free article

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

Rinat Bernstein-Molho et al. Cancer. .
Free article

Abstract

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.

Keywords: BRCA1 BRCA2; breast cancer; cancer susceptibility genes; non‐Ashkenazi Jewish; recurring pathogenic variants.

PubMed Disclaimer

References

REFERENCES

    1. Miki Y, Swensen J, Shattuck‐Eidens D, et al. A strong candidate for the breast and ovarian cancer susceptibility gene BRCA1. Science. 1994;266(5182):66‐71. doi:10.1126/science.7545954
    1. Wooster R, Bignell G, Lancaster J, et al. Identification of the breast cancer susceptibility gene BRCA2. Nature. 1995;378(6559):789‐792. doi:10.1038/378789a0
    1. American Society of Clinical Oncology. Policy statement update: genetic testing for cancer susceptibility. J Clin Orthod. 2003;21(12):2397‐2406. doi:10.1200/JCO.2003.03.189
    1. Statement of the American Society of Clinical Oncology. Genetic testing for cancer susceptibility, adopted on February 20, 1996. J Clin Orthod. 1996;14(5):1730‐1736. doi:10.1200/JCO.1996.14.5.1730
    1. Bedrosian I, Somerfield MR, Achatz MI, et al. Germline testing in patients with breast cancer: ASCO–Society of Surgical Oncology Guideline. J Clin Orthod. 2024;42(5). doi:10.1200/JCO.23.02225

MeSH terms