Prevalence of Pathogenic Variants in Postmenopausal Breast Cancer


This study suggested that PV prevalence among postmenopausal women may be high enough to warrant testing even in the absence of early diagnosis age or family history.

Data on the prevalence of pathogenic variants (PV) in breast cancer susceptibility genes among postmenopausal women, published in a research letter in JAMA, suggest that PV prevalence among this population may be high enough to warrant testing even in the absence of early diagnosis age or family history.1

Researchers suggested that these finding should inform testing guidelines, as currently most guidelines don’t address testing postmenopausal women with breast cancer in the absence of other risk factors. 

“There’s been a lot of controversy in the field as to whether every woman with breast cancer should receive genetic testing, 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,” lead author Allison Kurian, MD, MSc, associate professor of medicine and of epidemiology and population health at Stanford, said in a press release.1

Using the Women’s Health Initiative, which was a prospective study of morbidity and mortality that enrolled 161,808 postmenopausal women aged 50 to 79 years at 40 US sites from 1993 through 1998, researchers performed a nested case-control study. Women without personal history of breast cancer at Women’s Health Initiative enrollment who were diagnosed with invasive breast cancer (case participants) or remained cancer free (control participants) as of September 20, 2017 were included.

Overall, they compared 2,195 women diagnosed with breast cancer and 2,322 women without breast cancer. Next-generation sequencing and large rearrangement analysis using a panel of 28 genes was performed to classify variants as either pathogenic or likely pathogenic, of uncertain significance, or benign or likely benign. The researchers then compared the prevalence of cancer-associated mutations in 10 breast-cancer risk genes, including BRCA1 and BRCA2

PVs were detected in 241 women (148 case participants [6.74%; 95% CI, 5.73-7.87] and 93 control participants [4.01%; 95% CI, 3.24-4.88]; < 0.001). Moreover, A PV was detected in any breast cancer-associated gene in 3.55% (95% CI, 2.82-4.42) of case participants and 1.29% (95% CI, 0.87-1.84) of control participants (< .001). 

For BRCA1/2, PV prevalence was 2.21% (95% CI, 0.82-4.76) among those diagnosed when younger than 65 years and 1.09% (95% CI, 0.67-1.68) among participants diagnosed at 65 years or older. There was no trend by age for PV prevalence in BRCA1/2 (= .34) or other breast cancer–associated genes (= .54).

“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,” said Kurian. “We finally have a read on the likely benefit of testing this most common subgroup of breast cancer patients.” 

A notable limitation of the study, however, is that women chose to participate in the Women’s Health Initiative, so the study may not represent all US women, a small number of PVs, and wide confidence intervals in some subgroups.


1. Kurian AW, Bernhisel R, Larson K, et al. Prevalence of Pathogenic Variants in Cancer Susceptibility Genes Among Women With Postmenopausal Breast Cancer. JAMA. doi:10.1002/jama.2020.0229.

2. Older women with breast cancer may benefit from genetic testing [news release]. Stanford, California. Published March 10, 2020. Accessed March 17, 2020. 

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