Breast Cancer Coverage from Every Angle

Revelations About Genes Linked, and Not Linked, to Breast Cancer: Population-Based Study

By: Celeste L. Dixon
Posted: Monday, April 19, 2021

Because of ongoing “differing recommendations” regarding the selection of patients with breast cancer for clinical genetic testing and “considerable controversy” about which patients to test and which genes to include, Fergus J. Couch, PhD, of the Mayo Clinic in Rochester, Minnesota, and colleagues performed a large population-based study—including about 65,000 women from 17 breast cancer case-control studies in the CARRIERS consortium—to try to ascertain evidence-based answers. Among their findings, published in The New England Journal of Medicine, pathogenic variants in 16 of the 28 candidate breast cancer–predisposition genes, including the c.657_661del5 founder pathogenic variant NBN, were not associated with increased risk of breast cancer. Neither were BRIP1 and RECQL, both previously associated with an increased risk.

On the other hand, pathogenic variants in PALB2 were associated with an overall moderate risk of breast cancer, and PALB2 was identified as a high-risk gene (odds ratio = 8.04) among patients with a family history of breast cancer. Pathogenic variants in ATM, CDH1, and CHEK2 were associated with an increased risk of estrogen receptor–positive breast cancer. Not surprising, given earlier evidence, pathogenic variants in BRCA1 and BRCA2 were associated with a high risk of breast cancer, with respective odds ratios of 7.62 and 5.23.

Of note, the researchers reported, a relatively high proportion of non-Hispanic Black women with breast cancer have estrogen receptor–negative disease. The study found that pathogenic variants in BARD1, RAD51C, and RAD51D were associated with moderate risks of estrogen receptor–negative (and triple-negative) breast cancer with a weak association with overall risk.

“Especially among underserved, minority populations,” they wrote, “risk stratification…is an important method for identifying women at the highest risk of having a mutation.” Regarding “the general population,” they continued, they anticipate that their CARRIERS analysis “will inform cancer screening and other risk-management strategies for women with pathogenic variants in cancer-predisposition genes.”

Disclosure: The study authors’ disclosure information can be found at

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