Abstract PS3-03-16: Distribution of Molecular Subtypes of Hereditary Breast Cancer in Brazilian Patients according to Pathogenic or Likely Pathogenic Germline Genetic Variants

Abstract Objective: To assess the distribution of molecular subtypes of hereditary breast cancers, according to the presence of pathogenic or likely pathogenic germline genetic variants detected by multigene panel testing. Methods: A prospective cohort study was conducted from November 2021 to October 2022, involving women under follow-up at the high-risk outpatient clinic at the University of Campinas (UNICAMP). Patients were required to meet the following criteria: a personal history of luminal or HER2-positive breast cancer diagnosed before age 45, or triple-negative breast cancer diagnosed before age 60, along with at least one first- or second-degree relative with breast, ovarian, and/or prostate cancer, or who met the NCCN high-risk criteria (NCCN version 3.2021). Patients completed a questionnaire, after which they were referred for genetic testing. Following the test results, they received counseling based on the findings. Results: A total of 184 patients and 198 breasts were studied. Pathogenic variants (PV) or likely pathogenic variants (LPV) were detected in 36% (67/184) of the patients. Approximately 28% (51/184) were under 40 years of age, 30% (74/184) were non- Caucasian, and 49% (90/184) were premenopausal. General Analysis: The molecular subtypes most associated with pathogenic/probably pathogenic variants (PV/LPV) were Luminal B HER2-negative "like" (OR=11.76; CI 4.19-33.01) and triple-negative (OR=8.4; CI 3.45-20.43). These associations remained consistent even when the analysis was restricted to BRCA1 and BRCA2 genes only (OR=9.33; CI 2.00-29.99) (OR=9.03; CI 3.37-24.20) or to non-BRCA genes (OR=7.75;CI 2.96-29.44) (OR=3.48; CI 1.32-9.20) for Luminal B HER2-negative "like" triple-negative subtypes. Conclusion: Two molecular subtypes were associated with the presence of pathogenic or likely pathogenic variants in genes associated with hereditary breast cancer: Luminal B HER2-negative and triple-negative subtypes. Keywords: High risk; Germline variants; Genetic testing; Breast cancer; Molecular subtypes Citation Format: A. R. cabello, C. Cabello, S. Ramalho, C. E. Alem, S. R. Teixeira, L. R. Silva, G. S. Paiva, B. N. Duarte, M. Souza, T. cabello, D. I. Silva, A. Viaro, T. Gaspar, L. C. Zeferino. Distribution of Molecular Subtypes of Hereditary Breast Cancer in Brazilian Patients according to Pathogenic or Likely Pathogenic Germline Genetic Variants [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS3-03-16.