Abstract PS4-01-21: Genomic characterization and genetic testing gaps in early-onset breast cancer in Colombia

Abstract Background: Breast cancer (BC) in women under 50 years represents a biologically aggressive disease with distinct genomic features and higher hereditary burden. Latin American data on this subgroup remain limited. We aimed to describe the clinical and molecular characteristics of young BC patients in a comprehensive cancer center in Colombia, and to evaluate the yield of genetic testing. Methods: A retrospective cohort of 113 women <50 years diagnosed with BC at the Luis Carlos Sarmiento Angulo Cancer Treatment and Research Center (CTIC) between 2019 and 2024 was analyzed. Demographic, clinical, histopathologic, imaging, and molecular data were extracted. Tumor subtypes were defined based on ER, PR, and HER2 status. Germline sequencing was performed in 95% of cases (n=108). Chi-squared and t-tests were used to assess associations between mutation status, age, and clinical variables. Results: Among 108 women diagnosed with breast cancer at ≤50 years of age who underwent comprehensive germline genetic testing, 76 patients (70.4%) had complete immunohistochemical data, enabling subtype classification. The most common subtype was Luminal (n=36, 47.4%), followed by triple-negative (n=18, 23.7%) and HER2-enriched tumors (n=8, 10.5%). The luminal group showed a mutation frequency of 13.9% (5/36), while HER2-enriched tumors exhibited a rate of 12.5% (1/8). BRCA1 was the most frequent germline mutation in triple-negative tumors, identified in 18.2% (2/11) of cases. In contrast, Luminal and HER2-enriched subtypes showed a predominance of non-canonical mutations, including genes such as MUTYH, POLE, and APC, detected in 40.9% (9/22) and 14.3% (2/14) of cases, respectively. When considering all germline findings, 47 out of 108 patients (43.5%) harbored at least one germline alteration. The most frequently altered genes across the cohort were BRCA1 (7.4%), PALB2 (5.6%), BRCA2 (3.7%), and CHEK2 (1.9%). Additionally, 24.1% had variants in non-canonical genes, including both pathogenic and uncertain significance variants. Patients carrying germline mutations were diagnosed at a significantly younger age (mean 34.9 ± 6.1 years) compared to non-carriers (mean 41.8 ± 5.4 years; p < 0.001), emphasizing the contribution of hereditary predisposition to early-onset breast cancer and supporting the implementation of broad germline testing in all young patients, irrespective of tumor subtype. Conclusions: Germline pathogenic variants are frequent in early-onset breast cancer, particularly in triple-negative and Luminal subtypes. BRCA1 predominates in triple-negative cases, while PALB2 and CHEK2 are found in hormone receptor–positive tumors. Additionally, 24.1% of patients carried alterations in non-canonical genes, reflecting marked genomic heterogeneity. Mutation carriers were diagnosed at a significantly younger age, supporting early and comprehensive genetic testing in all young patients to guide personalized care and familial risk assessment. Citation Format: M. A. Bravo, D. C. Sotelo-Rodríguez, J. Caicedo, S. Cervera, A. Ruiz-Patiño, W. A. Mantilla, S. X. Franco. Genomic characterization and genetic testing gaps in early-onset breast cancer in Colombia [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 PS4-01-21.