Ancestry-specific risk of triple-negative breast cancer (TNBC) associated with germline pathogenic variants (PV) in hereditary cancer (CA) predisposition genes.

Abstract

10517 Background: TNBC represents ̃15% of invasive BC. Ancestry-specific variabilities in TNBC risk are well-described, with African American (AA) women experiencing higher incidence and mortality from TNBC than women of other races/ethnicities. Increased risk of TNBC has been associated with both rarer (e.g. RAD51C/D, BARD1) and more commonly detected (e.g. BRCA1/2, PALB2) germline PV in hereditary CA predisposition genes, but less is known about ancestry-specific TNBC risks for PV carriers. Methods: We examined clinical and genetic records from women referred for multigene CA panel testing (9/2013-5/2020). Multivariable logistic regression was used to test associations of PV in 13 genes with risk of TNBC after accounting for age, ancestry, and personal/family CA history. We analyzed each gene in the full cohort, and in subcohorts defined by self-reported ancestry. Effect sizes are expressed as odds ratios with 95% confidence intervals. Seven genes are not reported in ancestry-stratified analyses due to small numbers of PV carriers with TNBC. Results: From 627,219 individuals referred for multigene panel testing, 115,337 (18.4%) women with personal history of BC were identified, of whom 17,951 (15.6%) reported TNBC. Personal history of TNBC was reported more frequently in women of African ancestry (26.9%) than in women of European (13.9%) or Asian (11.7%) or Latinx ancestry (14.9%). Ancestry-stratified risks of TNBC associated with germline PVs are seen in the Table. Conclusions: While small samples sizes limit some gene-specific analyses, comparable ancestry-specific risks of TNBC were seen across the racial/ethnic groups examined here. [Table: see text]