Genetic Testing Benefits Postmenopausal Women with Breast Cancer

Germline genetic testing for pathogenic variants (PVs) in cancer susceptibility genes after breast cancer diagnosis may inform cancer treatment, prevention, and testing of relatives. Postmenopausal women with breast cancer had a threefold higher prevalence of pathogenic variants in breast cancer-associated genes than their cancer-free counterparts.

Whether testing should be performed depends partly on PV prevalence, which may be low in the general population but higher in women with risk factors (e.g., young diagnosis age, family history). For the best-characterized breast cancer susceptibility genes, BRCA1, BRCA2, or both (BRCA1/2), a minimum PV prevalence of 2.5% to 10% has been recommended for testing.


A team of medical scientists from Stanford University School of Medicine (Stanford, CA, USA) and their colleagues determine PV prevalence among women diagnosed with breast cancer after menopause versus the background prevalence among cancer-free postmenopausal women. The team analyzed data of women with banked DNA samples who participated in the Women’s Health Initiative, which enrolled more than 160,000 postmenopausal women aged 50 to 79 years between 1993 and 1998. They compared the prevalence of breast cancer-associated mutations in 10 genes, BRCA1, BRCA2, ATM, BARD1, CDH1, CHEK2, NBN, PALB2, STK11 and TP53, among 2,195 women diagnosed with breast cancer (median age at diagnosis, 73 years; 66.3% white) versus 2,322 women without breast cancer (median age at last follow-up, 81 years; 84.9% white).

The investigators reported that pathogenic variants were detected among 6.74% of women with breast cancer compared with 4.01% of women without breast cancer. Results showed pathogenic variants in one of the 10 breast cancer-associated genes among 3.55% of women with breast cancer compared with 1.29% of cancer-free women. Moreover, 2.21% of women diagnosed at younger than age 65 years carried BRCA1 or BRCA2 mutations compared with 1.09% of women diagnosed at age 65 years or older. Only 30.8% of women with breast cancer and 20% of women without breast cancer who carried BRCA1 or BRCA2 mutations appeared likely to have met current National Comprehensive Cancer Network guidelines for genetic testing.

Allison W. Kurian, MD, MSc, associate professor of medicine, and lead author of the study, said, “Although genetic testing is increasingly relevant for the care of patients with cancer, little was known about the prevalence of inherited mutations in cancer susceptibility genes among the most common group of women with breast cancer who are those diagnosed after menopause and without a strong family history of cancer.” The study was published on March 10, 2020 in the journal JAMA.

Related Links:
Stanford University School of Medicine