FOXC1 expression predicts capecitabine efficacy in triple-negative breast cancer patients from the GEICAM_CIBOMA trial.

PURPOSE: In a prespecified GEICAM_CIBOMA trial (NCT00130533) correlative analysis, PAM50 non-basal (non-BLBC) status distinguished triple-negative breast cancer (TNBC) patients most likely to benefit from adjuvant capecitabine. The standardized FOXC1 Immunohistochemistry (IHC) test has demonstrated...

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Detalhes bibliográficos
Autores: Rojo F, Taylor CR, Barrios C, Torrecillas L, Ruiz-Borrego M, Perez-Buira S, Bines J, Guerrero-Zotano A, Garcia-Saenz JA, Torres R, de la Haba-Rodriguez J, Ayala F, Gomez H, Llombart A, Rodriguez de la Borbolla M, Baena-Cañada JM, Barnadas A, Calvo L, Herranz J, Rincon R, Caballero R, Bermejo B, Ray PS, Martín M
Formato: artículo
Estado:Versión publicada
Fecha de publicación:2025
País:España
Recursos:Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana (FISABIO)
Repositorio:r-FISABIO. Repositorio Institucional de Producción Científica
OAI Identifier:oai:fisabio.fundanetsuite.com:p19065
Acesso em linha:https://fisabio.portalinvestigacion.com/publicaciones/19065
Access Level:acceso abierto
Palavra-chave:ADJUVANT CAPECITABINE
NEOADJUVANT CHEMOTHERAPY
CYCLOPHOSPHAMIDE
EPIRUBICIN
DOCETAXEL
THERAPY
Descrição
Resumo:PURPOSE: In a prespecified GEICAM_CIBOMA trial (NCT00130533) correlative analysis, PAM50 non-basal (non-BLBC) status distinguished triple-negative breast cancer (TNBC) patients most likely to benefit from adjuvant capecitabine. The standardized FOXC1 Immunohistochemistry (IHC) test has demonstrated strong reliability in classifying the BLBC subtype throughout TNBC cohorts. This translational analysis aimed to evaluate the prognostic/predictive significance of BLBC classification by FOXC1 IHC in the phase III GEICAM_CIBOMA clinical trial. EXPERIMENTAL DESIGN: Tumor tissues from TNBC patients randomized to standard (neo)adjuvant chemotherapy followed by capecitabine vs. observation were analyzed using the standardized FOXC1 IHC test to assess its BLBC/non-BLBC TNBC subtyping capacity as distant relapse-free survival (DRFS) clinical outcome predictor of capecitabine benefit (exploratory endpoints: disease-free survival (DFS), overall survival (OS), RFS). RESULTS: 705 patients (80.5%) from GEICAM_CIBOMA trial were evaluable for FOXC1 expression analysis, with balanced distribution between trial's treatments. FOXC1 Score (VFOXC1)-based subtyping demonstrated a strong association (AUC 0.87; 95% CI, 0.84-0.91) and agreement (Kappa index 0.43; P < 0.0001) with PAM50 molecular subtyping. VFOXC1 non-BLBC TNBC subtype was a significant independent predictor of clinical benefit with capecitabine for DRFS (HR, 0.44; 95% CI, 0.25-0.76; P = 0.003). This predictive effect of VFOXC1 non-BLBC on capecitabine efficacy was further confirmed at DFS (HR=0.47; 95%CI 0.28-0.78; p=0.003), OS (HR=0.48; 95%CI 0.24-0.96; p=0.038) and RFS (HR=0.39; 95%CI 0.22-0.72; p=0.002). CONCLUSIONS: This ambispective GEICAM_CIBOMA translational analysis validated FOXC1-based basal-like/non-basal subtyping as a pragmatic alternative to PAM50 subtyping and independently predicted the benefit of adding capecitabine to standard (neo)adjuvant chemotherapy in TNBC.

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