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

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.

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Journal
Breast Cancer Research
Published
2026-08-28
DOI
https://doi.org/10.1186/s13058-026-02369-7
Primary Topic
HER2/EGFR in Cancer Research
Type
article
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article

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

Laura Torrecillas, VEGA IRANZO GONZALEZ-CRUZ, Isaura Fernández, Miguel Ángel Seguí et al.
Breast Cancer Research
HER2/EGFR in Cancer Research
article

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

Laura Torrecillas, VEGA IRANZO GONZALEZ-CRUZ, Isaura Fernández, Miguel Ángel Seguí, Federico Rojo, Roberto Torres, Antonio Llombart‐Cussac, Raúl Rincón, Jesús Herránz, Ángel Guerrero‐Zotano, Sara López‐Tarruella, María Amenedo, María Rodríguez de la Borbolla, Rosalía Caballero, Laura Pérez Michel, Sandra Pérez‐Buira, Miguel Martín, Carlos H. Barrios, José A. García-Sáenz, Juan de la Haba-Rodriguez, Jose G. M. Segalla, Henry Gomez, Jose Bines, Elena Garcia-Martinez, Eduardo Martinez de Dueñas, Begoña Bermejo, Alvaro Rodriguez-Lescure, Jeferson Vinholes, Jesus Cardenas, Manuel Ruiz-Borrego
article en

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.

Breast Cancer Research
University Hospital Complex Of Vigo (ES), Hospital General Universitario Gregorio Marañón (ES), Sonora Institute of Technology (MX), Eastern Cooperative Oncology Group (US), Hospital General Universitario Morales Meseguer (ES), Instituto Maimónides de Investigación Biomédica de Córdoba (ES), Consorcio Hospitalario Provincial de Castellón (ES), Centro Oncológico de Galicia (ES), Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (ES), Fundación Instituto Valenciano de Oncología (ES), Hospital Amaral Carvalho (BR), Corporació Sanitària Parc Taulí (ES), Hospital General Universitario de Elche (ES), Hospital Arnau de Vilanova (ES), Instituto Nacional de Enfermedades Neoplásicas (PE), Hospital de Sabadell (ES), Hospital General Universitario De Valencia (ES), Hospital Universitario Fundación Jiménez Díaz (ES), Hospital São Lucas da PUCRS (BR), Complexo Hospitalario Universitario A Coruña (ES), Instituto Nacional de Câncer - INCA (BR), Instituto Nacional del Cáncer (CL), Hospital Universitario de Valme (ES), Hospital Universitario Virgen del Rocío (ES), INCLIVA Health Research Institute (ES), GEICAM – Spanish Breast Cancer Group (ES), Universidad Autónoma de Madrid (ES), Institute for Social Security and Services for State Workers (MX), Universidad de Colima (MX)
F. Hoffmann-La Roche, Instituto de Salud Carlos III
Good health and well-being
Openalex Percentile: Top 13%
HER2/EGFR in Cancer Research
DOIOpen Access PDFOpenAlex
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