The breast cancer risks associated with common germline mutations in predisposition genes were identified for the general population using a set of studies that make up the CARRIERS consortium. The study findings were presented during a poster discussion at the 2019 San Antonio Breast Cancer Symposium (SABCS) in Texas.1
“As clinical hereditary cancer genetic testing is already provided to many women at increased risk and may soon be offered to all breast cancer patients; population-based risk estimates associated with predisposition gene mutations will be needed for appropriate clinical management of these patients,” the study authors reported.
The current analysis was based on data from 32,247 patients with breast cancer and 32,544 matched individuals who were cancer-free, all of whom supplied germline DNA for sequencing. Among the 24 genes evaluated for mutations, 12 were for breast cancer predisposition genes: ATM, BARD1, BRCA1, BRCA2, CDH1, CHEK2, NF1, PALB2, PTEN, RAD51C, RAD51D, and TP53.
A higher percentage of cases had a predisposition-gene mutation in the germline compared with the matched controls (5% vs 1.7%, respectively). An adjusted case-control association analysis revealed that for the general population, BRCA1 (overall response [OR], 7.35; 95% CI, 5.17-10.81), BRCA2 (OR, 5.28; 95% CI, 4.13-6.85), PALB2 (OR, 3.66; 95% CI, 2.58-5.33), and ATM mutations (OR, 1.82; 95% CI, 1.46-2.27) were linked to a significant increased risk of breast cancer.
In a separate analysis of studies that comprise the CARRIERS consortium — an analysis that was also featured in a poster during SABCS 2019 — polygenic risk scores were found to be associated with breast cancer risk both in carriers and noncarriers of predisposition genes.2
“We anticipate that the results from this study will inform on cancer screening and other risk-management strategies for women in the general population with mutations in predisposition genes,” the study authors wrote.
- Cough FJ, Chungling H, Hart SN, et al. Population-based breast cancer risk estimates for predisposition gene mutations: Results from the CARRIERS study. Poster presentation at: 2019 San Antonio Breast Cancer Symposium; December 10-14, 2019; San Antonio, TX. Abstract PD3-01.
- Gao C, Polley EC, Hu C, et al. Polygenic risk scores provide clinically meaningful risk stratification among women carrying moderate penetrance pathogenic variants in breast cancer predisposition genes: Results from the CARRIERS study. Poster presentation at: 2019 San Antonio Breast Cancer Symposium; December 10-14, 2019; San Antonio, TX. Abstract PD3-02.
This article originally appeared on Cancer Therapy Advisor