Postmenopausal women newly diagnosed with breast cancer who lack hereditary risk factors for this disease might benefit from genetic testing for inherited cancer-associated mutations, according to Stanford University researchers.

These patients generally fall outside guideline recommendations for breast cancer-related genetic testing. However, a nested case control study of Women’s Health Initiative participants found that 3.55% had pathogenic variants in breast cancer-associated genes, about a 3-fold higher prevalence than participants who did not have breast cancer. Moreover, women whose breast cancer had been diagnosed when they were younger than age 65 had about the same probability of pathogenic BRCA1/2 variants (2.5%) as women of Ashkenazi Jewish heritage, for whom genetic testing is recommended.

"There's been a lot of controversy in the field as to whether every woman with breast cancer should receive genetic testing," said first author Allison Kurian, MD, MSc, an associate professor of medicine and of epidemiology and population health at Stanford, "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."

Kurian went on to add, “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 and her colleagues studied 4,500 participants in the long-running Women’s Health Initiative. In a group of 2,195 postmenopausal women aged 50 to 79 at enrollment who had been diagnosed with invasive breast cancer and a control group of 2,322 who remained cancer free, the researchers analyzed via next-generation sequencing and large rearrangement analysis 28 genes, including 10 associated with breast cancer: BRCA1/2, ATM, BARD1, CDH1, CHEK2, NBN, PALB2, STK11, and TP53.

This analysis identified pathogenic variants in 6.74% of case subjects and 4.01% of control subjects and pathogenic breast cancer-associated variants in 3.55% of case subjects and 1.29% of control subjects. Just one-third of women with pathogenic breast cancer-associated variants would have met current guideline recommendations for breast cancer genetic testing.

Kurian and her coauthors suggested these findings should inform testing guidelines. They also suggested that the prevalence of pathogenic variants in postmenopausal women with breast cancer might be high enough to substantiate testing in this group “even in the absence of early diagnosis age or family history.”