July 20, 2017
2 min read

Genetic testing for breast cancer recommended for all Ashkenazi Jewish women

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Women of Ashkenazi Jewish ancestry who do not harbor one of the founder mutations in BRCA1 or BRCA2 may develop breast cancer because of a damaging mutation in another breast cancer gene, according to a multicenter study published in JAMA Oncology.

“Many of these cancers could be prevented by offering genetic testing to all [Ashkenazi Jewish] women before they develop cancer as part of routine medical care,” Mary-Claire King, PhD, genetic researcher and professor of genome sciences and medicine at University of Washington, and colleagues wrote.

Mary-Claire King

About one of every 40 women with Ashkenazi Jewish ancestry who trace their roots to Central or Eastern Europe harbor a mutation in the BRCA1 or BRCA2 gene, compared with one out of every 800 members of the general population, according to the CDC.

Genetic mutations in BRCA1 and BRCA2 increase the risk for breast and ovarian cancer. Researchers evaluated the likelihood that women with breast cancer and Ashkenazi Jewish ancestry who did not carry one of the founder mutations would carry another cancer-predisposing mutation.

The analysis included 1,007 women from 12 major cancer centers with a first diagnosis of invasive breast cancer who participated in The New York Breast Cancer Study from 1996 to 2000. All the women identified themselves and all four of their grandparents as Ashkenazi Jewish.

Age ranges included women younger than 40 years (n = 106), 40 to 49 years (n = 322), 50 to 59 years (n = 303) and 60 years or older (n = 276).

Researchers sequenced genomic DNA from the patients for 23 known and candidate breast cancer genes using BROCA, a targeted multiplexed gene panel developed by University of Washington. Data collection occurred from July 10, 2014, through March 10, 2017.

A total of 903 women carried none of the three founder mutations in BRCA1 or BRCA2. Among them, 0.8% (n = 7) carried a different mutation in BRCA1 or BRCA2 and 3.4% (n = 31) carried a damaging mutation in another breast cancer gene (CHEK2, n = 29; BRIP1, n = 1; NBN, n = 1).

Overall, 14.1% (n = 142) of Ashkenazi Jewish women with breast cancer carried a germline mutation responsible for their disease — 11% in BRCA1 or BRCA2, and 3.1% in CHEK2 or another breast cancer gene.

Of all 142 inherited predispositions to breast cancer, 73.8% (n = 104) occurred due to a BRCA1 or BRCA2 founder allele, 4.9% (n = 7) to another BRCA1 or BRCA2 mutation, and 21.8% (n = 31) to a mutation in another gene.


Of the 111 patients with BRCA1 or BRCA2 mutations, 57 (51.4%) had a mother or sister with breast or ovarian cancer and 54 patients (48.6%) did not.

“Approximately half of the patients with a damaging mutation in any breast cancer gene did not have a family history suggesting inherited predisposition,” King and colleagues wrote. “Mutations in these families were likely inherited from fathers, and the combination of small family size and chance in genetic transmission yielded few female relatives carrying mutant alleles. Therefore, to limit genetic testing to patients with a suggestive family history is to miss about 50% of patients with actionable mutations.” – by Chuck Gormley

Disclosure: The Breast Cancer Research Foundation funded this study. King reports she is an American Cancer Society research professor.