Trop-2 overexpression as a prognostic marker in early triple-negative breast cancer: results from the GEICAM_CIBOMA trial

Abstract

Trophoblast cell-surface antigen 2 (Trop-2) is a key therapeutic target in metastatic triple-negative breast cancer (TNBC), yet its prognostic significance in early-stage disease remains poorly defined. We evaluated Trop-2 expression and its clinical impact within a sub-cohort of the phase III GEICAM_CIBOMA trial (NCT00130533). Trop-2 membrane expression was assessed by immunohistochemistry (H-score) in a pragmatic sub-cohort of 70 patients, representative of the trial’s intention-to-treat population. High/medium (positive) Trop-2 expression (H-score ≥ 100) was observed in 74.3% of cases. Elevated Trop-2 significantly correlated with higher histological grade ( p = 0.032) and reduced distant relapse risk ( p = 0.031). Biologically, Trop-2-high tumors trended toward PAM50 non-basal-like subtypes (19% vs. 6%) and higher stromal TILs (≥ 50%; 21% vs. 11%). Notably, high Trop-2 expression emerged as an independent prognostic factor for improved distant relapse-free survival (DRFS; HR = 0.31, p = 0.008), disease-free survival (DFS; HR = 0.38, p = 0.022), and overall survival (OS; HR = 0.37, p = 0.031) in survival Cox multivariate models. In early-stage TNBC, high Trop-2 membrane expression is an independent prognostic biomarker associated with favorable clinical outcomes. Despite the inherent limitations of the sample size, the internal validity of these findings is supported by the balanced cohort and consistency across survival endpoints. These results provide a biological rationale for investigating Trop-2-directed strategies in the curative setting, although its predictive value for chemotherapy benefit requires further validation in larger prospective trials.