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Genetic testing may benefit this population


New research shows that these certain patients with breast cancer can benefit from genetic testing for all breast cancer genes.

In the Ashkenazi Jewish population, the mutation profile of BRCA1 and BRCA2 is distinctive, with three ancient founder mutations in these two genes. Combined, these three mutations are responsible for 10% of invasive breast cancer among Ashkenazi Jewish women.

The relatively high frequency of the Ashkenazi Jewish founder mutations in BRCA1 and BRCA2 has enabled the effective use of cancer genetics services by Jewish women, according to research published online July 20, 2017, in JAMA Oncology.

For Ashkenazi Jewish patients with breast cancer who do not carry one of these three founder mutations, the chance of carrying some other pathogenic mutation in BRCA1 or BRCA2, or a pathogenic mutation in a different breast cancer gene, is not known. This information, however, would be valuable to patients and their families for cancer prevention and treatment.


A group of researchers, led by Mary-Claire King, PhD, Department of Medicine, University of Washington in Seattle, conducted a study to determine the frequency of cancer-predisposing mutations other than the BRCA1 and BRCA2 founder mutations among patients of Ashkenazi Jewish ancestry with breast cancer.

Should Ashkenazi Jewish women with breast or ovarian cancer who have negative results for the three founder mutations obtain complete sequencing of BRCA1 and BRCA2 so as not to miss some other mutation? Should these patients also be tested for mutations in other breast cancer genes?

“We addressed these questions by sequencing all known breast and ovarian cancer genes in genomic DNA, which was provided by participants of the New York Breast Cancer Study (NYBCS), a longstanding cohort of Ashkenazi Jewish women with a primary diagnosis of invasive breast cancer,” the authors said.

The result, they said, is that Ashkenazi Jewish patients with breast cancer can benefit from genetic testing for all breast cancer genes. Comprehensive sequencing would provide complete relevant genetic information.

Next: A deeper dive



In the study, genomic DNA of women from 12 major cancer centers with a first diagnosis of invasive breast cancer who identified themselves and all four grandparents as Ashkenazi Jewish and participated from 1996 to 2000 was sequenced for 23 known and candidate breast cancer genes. Data analysis was performed from July 10, 2014, to March 10, 2017.

Of the 1,007 patients in the study, 903 had no founder mutations in BRCA1 or BRCA2; of those 903 patients, 7 (0.8%) carried another pathogenic mutation in BRCA1 or BRCA2, and 31 (3.4%) carried a pathogenic mutation in another breast cancer gene.

Of all inherited predispositions to breast cancer in the NYBCS, 73.8% (104 of 142) were due to a BRCA1 or BRCA2 founder mutation, 4.9% (7 of 142) to another BRCA1 or BRCA2 mutation, and 21.8% (31 of 142) to a mutation in another gene. Overall, 14.1% (142 of 1,007) of Ashkenazi Jewish patients with breast cancer in the NYBCS carried a germline mutation responsible for their disease: 11.0% (111 of 1,007) in BRCA1 or BRCA2, and 3.1% (341 of 1,007) in another breast cancer 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.

The authors concluded that, “The most recent national screening guidelines recommend genetic testing for all Ashkenazi Jewish patients with breast cancer. This recommendation is fine, but testing women only after they develop cancer severely limits the power of precision medicine.

“To discover a mutation only after cancer is diagnosed is a missed opportunity to have prevented that cancer,” the authors added. “Many of these cancers could be prevented by offering genetic testing as described here to all women before they develop breast cancer, as part of routine medical care.”

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