Abstract

Breast cancer and ovarian cancer patients increasingly undergo germline genetic testing. However, little is known about cancer-specific mortality among carriers of a pathogenic variant (PV) in BRCA1/2 or other genes in a population-based setting.Georgia and California Surveillance Epidemiology and End Results (SEER) registry records were linked to clinical genetic testing results. Women were included who had stages I-IV breast cancer or ovarian cancer diagnosed in 2013-2017; received chemotherapy; and linked to genetic testing results. Multivariable Cox proportional hazard models were used to examine the association of genetic results with cancer-specific mortality.22,495 breast and 4,320 ovarian cancer patients were analyzed, with a median follow-up of 41 months. PVs were present in 12.7% of breast cancer patients with estrogen and/or progesterone receptor-positive, HER2-negative cancer, 9.8% with HER2-positive cancer, 16.8% with triple-negative breast cancer and 17.2% with ovarian cancer. Among triple-negative breast cancer patients, cancer-specific mortality was lower with BRCA1 (hazard ratio [HR] = 0.49, 95% confidence interval [CI] = 0.35-0.69) and BRCA2 PVs (HR?=?0.60, 95% CI?=?0.41-0.89), and equivalent with PVs in other genes (HR?=?0.65, 95% CI?=?0.37-1.13), versus non-carriers. Among ovarian cancer patients, cancer-specific mortality was lower with PVs in BRCA2 (HR?=?0.35, 95% CI?=?0.25-0.49) and genes other than BRCA1/2 (HR?=?0.47, 95% CI?=?0.32-0.69). No PV was associated with higher cancer-specific mortality.Among breast cancer and ovarian cancer patients treated with chemotherapy in the community, BRCA1/2 and other gene PV carriers had equivalent or lower short-term cancer-specific mortality than non-carriers. These results may reassure newly diagnosed patients and longer follow-up is ongoing.

View details for DOI 10.1093/jnci/djab151

View details for PubMedID 34373918