BRCA1, HRR Pathway Genes and Ancestry in Triple-Negative Breast Cancer: Insights on Germline Risk and Survival from a Brazilian Cohort Study

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All articles of this category (opens in new window) Address for correspondence Dirce Maria Carraro (dirce.carraro@accamargo.org.br) Triple-negative breast cancer (TNBC) is an aggressive and heterogeneous subtype of breast cancer often linked to early onset and African ancestry. A significant proportion of TNBC cases are hereditary, mainly associated with BRCA1, a key gene in the homologous recombination repair (HRR) pathway. Disruption of this pathway due to germline pathogenic variants in BRCA1 and other HRR genes results in homologous recombination deficiency, a phenotype associated with sensitivity to PARP inhibitors. The role of HRR genes and genetic ancestry in TNBC outcomes has not been well studied in an admixed population. We analyzed 321 Brazilian TNBC patients using NGS panels and assessed molecular ancestry in 248 patients using a microarray assay. We identified GPVs in 28.9% of cases, with the highest frequency in BRCA1 (14.6%). BRCA1 carriers were younger at diagnosis and more likely to present early-onset and bilateral tumors. Carriers of BRCA1 and other-HRR genes showed significantly improved 3-year progression-free survival (PFS). Patients with predominant African ancestry had worse 3y-PFS than those with European ancestry. Our findings emphasize the relevance of BRCA1 and distinct clinical patterns associated with other HRR genes in TNBC predisposition and highlight ancestry-related survival disparities in the Brazilian population, whose African ancestry differs from that of African Americans, warranting further validation. Publication History Article published online: 26 June 2026 © 2026. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution 4.0 International License, permitting copying and reproduction so long as the original work is given appropriate credit (https://creativecommons.org/licenses/by/4.0/) Thieme Revinter Publicações Ltda. Rua Rego Freitas, 175, loja 1, República, São Paulo, SP, CEP 01220-010, Brazil Bibliographical Record Rafael Canfield Brianese, Karina Miranda Santiago, Gabriel Bandeira do Carmo, Leticia Santos Pimentel, Giovana Tardin Torrezan, Rafaella Ormond, Marcos Leite Santoro, Marcelo Moreno, Ândrea Kely Campos Ribeiro dos Santos, Marina de Brot, Fabiana Baroni Alves Makdissi, Solange Moraes Sanches, Jose Claudio Casali da Rocha, Dirce Maria Carraro. BRCA1, HRR Pathway Genes and Ancestry in Triple-Negative Breast Cancer: Insights on Germline Risk and Survival from a Brazilian Cohort Study. Brazilian Journal of Oncology 2026; 22. DOI: 10.1055/s-0046-1825380

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