A study published in The New England Journal of Medicine estimated the prevalence and risk of breast cancer among known pathogenetic variants in known breast cancer-predisposing genes.
In the population-based, case-control study, researchers performed gene sequencing via a custom multigene amplicon-based panel to identify germline pathogenic variants in 28 cancer-predisposition genes. They analyzed the occurrence of 12 genes that have been tied to breast cancer among 32,247 women with breast cancer and 32,544 female controls without breast cancer. The participants were included from population-based studies in the Cancer Risk Estimates Related to Susceptibility consortium.
Researchers detected pathogenic variants in the 12 established breast cancer-predisposition genes in 5.03% of patients with breast cancer and in 1.63% of controls. Pathogenic variants in BRCA1 (odds ratio [OR], 7.62; 95% confidence interval [CI], 5.33-11.27) and BRCA2 (OR, 5.23; 95% CI, 4.09-6.77) were associated with an eightfold and fivefold high risk of breast cancer, respectively. Pathogenic variants in PALB2 were associated with a moderate risk of breast cancer (OR, 3.83; 95% CI, 2.68-5.63).
Pathogenic variants in BARD1, RAD51C, and RAD51D were associated with increased risks of estrogen receptor (ER)-negative breast cancer and triple-negative breast cancer, while pathogenic variants in ATM, CDH1, and CHEK2 were associated with an increased risk of ER-positive breast cancer. Pathogenic variants in 16 candidate breast cancer-predisposition genes, including the c.657_661del5 founder pathogenic variant in NBN, were not associated with an increased risk of breast cancer.
While the researchers observed no differences in the odds of having a mutation among racial groups overall, certain mutations were more common in certain groups—for example, Black women were more likely to have mutations linked to triple-negative cancers.
“These estimates can inform cancer testing and screening and improve clinical management strategies for women in the general population with inherited pathogenic variants in these genes,” the researchers concluded.