Ten-year overall survival in patients with breast cancer and pathogenic/probably pathogenic germ line variants who attend genetic consultation at an oncology center in the city of Medellín

Abstract

Germline pathogenic or likely pathogenic variants (P/LPVs) are present in approximately 10% of breast cancer cases. However, the clinical outcomes and genetic distribution in Latin American populations remain understudied. This study aimed to estimate 10-year overall survival (OS) and assess prognostic factors in breast cancer patients carrying germline P/LPVs who were treated at a Colombian oncology center. This retrospective cohort study included 259 women with breast cancer and confirmed P/LPVs identified through multigene panel testing between 2018 and 2024. Demographic, clinical, tumor, and treatment characteristics were analyzed. OS was estimated via Kaplan‒Meier and Cox regression models. The median follow-up was 45 months (IQR: 40–55), with administrative censoring at 120 months. BRCA2 (40.9%) and BRCA1 (13.5%) were the most frequent variants. The estimated 10-year OS was 75% (95% CI: 70–80%), based on Kaplan–Meier estimates, acknowledging limited long-term follow-up. Patients with TP53 and CHEK2 variants showed higher OS estimates, whereas BRCA1 and PALB2 were associated with lower OS. In multivariate analysis, metastatic stage (HR = 8.16, 95% CI: 2.39–27.9) and BRCA1 variants (HR = 1.55, 95% CI: 1.30–5.97) remained significant predictors of OS. No statistically significant survival differences were observed according to risk-reducing surgeries. Findings related to less frequent variants are exploratory and should be interpreted with caution. In this Colombian cohort, BRCA2 was the most prevalent variant, and BRCA1 was associated with a higher risk of death. These results are descriptive and should be interpreted in the context of limited follow-up duration. The findings support the integration of germline testing into oncologic care and highlight the need for larger, prospective studies to validate long-term outcomes.