Cancer-specific mortality associated with germline genetic testing results among women with breast cancer or ovarian cancer treated with chemotherapy.

Abstract

10517 Background: Breast and ovarian cancer patients increasingly undergo germline genetic testing. While studies suggest a greater chemotherapy benefit for carriers of BRCA1/2 pathogenic variants, little is known about whether pathogenic variants in other genes are associated with cancer mortality. Methods: Georgia and California Surveillance, Epidemiology and End Results (SEER) registry records of women diagnosed with breast cancer or ovarian cancer from 2013-2017 were linked to results of clinical germline genetic testing from four participating laboratories. Patients were included if they linked to a genetic result, had stages I-III breast cancer or I-IV epithelial ovarian cancer and received chemotherapy. Multivariable Cox proportional hazard models were used to examine the association of genetic results, demographic and clinical factors with cancer-specific mortality. Results: 21,348 breast and 4,320 ovarian cancer patients were analyzed with median follow-up of 41 months. Pathogenic variants were present in 12% of patients with estrogen and progesterone receptor-positive, HER2-negative breast cancer, 9% with HER2-positive breast cancer, 17% with triple-negative breast cancer and 18% with ovarian cancer. Pathogenic variants were most common in BRCA1/2, CHEK2, PALB2, ATM and BRIP1. Among triple-negative breast cancer patients, mortality was lower with pathogenic variants in BRCA1 (hazard ratio (HR) 0.27, 95% confidence interval (CI) 0.17-0.45) and genes other than BRCA1/2 (HR 0.33, CI 0.13-0.81) versus no pathogenic variant. Genetic results were not associated with mortality in other breast cancer subtypes. Among ovarian cancer patients, mortality was lower with pathogenic variants in BRCA2 (HR 0.36, CI 0.26-0.49) and in genes other than BRCA1/2 (HR 0.48, CI 0.33-0.70). Conclusions: Among breast and ovarian cancer patients treated with chemotherapy, those with germline pathogenic variants in several cancer-associated genes had equivalent or lower short-term mortality than those testing negative. These results may guide patient counseling and clinical trial design.