Key clinical point: Protein-truncating variants (PTV) of 9 breast cancer (BC) risk genes showed substantial differences in tumor pathology and were generally associated with triple-negative (TN) or high-grade disease.
Major finding: BRCA1 showed the highest association for TN disease (odds ratio [OR] 55.32; 95% CI 40.51-75.55) and ATM variants for the hormone receptor-positive (HR+) erb-b2 receptor tyrosine kinase 2-negative (ERBB2−) high-grade subtype (OR 4.99; 95% CI 3.68-6.76). RAD51C (OR 6.19; 95% CI 3.17-12.12), RAD51D (OR 6.19; 95% CI 2.99-12.79), and BARD1 (OR 10.05; 95% CI 5.27-19.19) were most strongly associated with TN disease. PALB2 PTVs showed higher ORs for HR+ERBB2− high-grade subtype (OR 9.43; 95% CI 6.24- 14.25) and TN disease (OR 8.05; 95% CI 5.17-12.53).
Study details: This was a case-control analysis of the BRIDGES study including 42,680 patients with BC who were matched with 46,387 healthy controls.
Disclosures: This study was funded by the European Union Horizon 2020 research and innovation program, Wellcome Trust, and several other sources. The authors declared receiving grants, honorariums, personal fees, or awards from several sources.
Source: Breast Cancer Association Consortium. JAMA Oncol. 2022 (Jan 27). Doi: 10.1001/jamaoncol.2021.6744.