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Inherited Mutations in Postmenopausal Breast Cancer Patients Suggest Genetic Testing Is Warranted

NEW YORK – Women who develop breast cancer later in life may benefit from genetic testing, a new analysis has found, even though current guidelines for testing don't include them.

Genetic testing recommendations for breast cancer weigh factors such as age at diagnosis and family history of cancer. But Stanford University's Allison Kurian and her colleagues noted in their study, published on Tuesday in the Journal of the American Medical Association, that most guidelines don't address testing in postmenopausal women without familial risk factors, as there is not much data on the prevalence of pathogenic variants in this population. 

Using data from the Women's Health Initiative, they found that more than 3 percent of postmenopausal women with breast cancer but no other disease risk factors carried pathogenic variants in breast-cancer linked genes.

"There's been a lot of controversy in the field as to whether every woman with breast cancer should receive genetic testing," Kurian said in a statement, "in part because we didn't know how prevalent cancer-associated mutations are in this largest subgroup of newly diagnosed people — that is, women who develop breast cancer after menopause without the presence of any known hereditary risk factors." 

Last year, the American Society of Breast Surgeons recommended that genetic testing be available to all breast cancer patients, while the National Comprehensive Cancer Network recommended in December that breast cancer patients' personal cancer history and family history be used to determine the appropriateness of testing. Later that month, the American College of Medical Genetics and Genomics said all breast cancer patients should be assessed to determine whether they should undergo germline genetic testing. It did not, though, recommend all breast cancer patients receive such testing.

To ascertain the prevalence of cancer-linked mutations among older women diagnosed with breast cancer, Kurian and her colleagues conducted a nested case-control study using data collected by the Women's Health Initiative, a prospective study of morbidity and mortality in 161,808 postmenopausal women in the US. Their analysis included 2,195 women diagnosed with breast cancer but no other risk factors for the disease, and 2,322 control women who remained cancer-free. Samples collected from the participants underwent next-generation sequencing and rearrangement analysis to look for alterations affecting more than two dozen genes, including BRCA1, BRCA2, TP53, and CHEK2.

They uncovered pathogenic variants in 148 women with breast cancer, as compared to 93 in control women. Overall, a pathogenic variant in any breast cancer gene was present in 3.55 percent of cases, but only 1.29 percent of controls.

Additionally, 2.21 percent of women who were younger than 65 years at the time of their diagnosis had a BRCA1 or BRCA2 variant, a prevalence the researchers noted was similar to that of Ashkenazi Jewish individuals, for whom testing is recommended. Of those women in whom BRCA1 or BRCA2 mutations were found, only 30 percent met guidelines for testing, the researchers noted.

"Now we know that the prevalence of cancer-associated BRCA1 and BRCA2 mutations in women diagnosed with breast cancer after menopause rivals that in women of Ashkenazi Jewish descent — a population that is currently encouraged to discuss genetic testing with their doctors," Kurian said. "We finally have a read on the likely benefit of testing this most common subgroup of breast cancer patients."