FOXC1 Expression Predicts Capecitabine Efficacy in Patients with Triple-Negative Breast Cancer from the GEICAM_CIBOMA Trial
Rojo, Federico (Hospital Universitario Fundación Jiménez Díaz)
Torrecillas, Laura (Centro Medico Nacional 20 de Noviembre ISSSTE. CDMX)
Ruiz-Borrego, Manuel (Hospital Universitario Virgen del Rocío (Sevilla, Andalusia))
Bines, Jose (National Cancer Institute (INCA))
Torres, Roberto (Instituto Nacional del Cancer)
de la Haba Rodríguez, Juan Rafael (Instituto Maimonides de Investigacion Biomedica de Cordoba (IMIBIC)-Hospital Universitario Reina Sofia)
Llombart, Antonio (Hospital Arnau de Vilanova)
Barnadas i Molins, Agustí (Institut de Recerca Sant Pau)
Bermejo, Begoña (Hospital Clínic Universitari (València))
Martín Jiménez, Miguel (Universidad Complutense de Madrid)
Taylor, Clive R. (Onconostic Technologies. Inc. (OT))
Barrios, Carlos (Clinica Hospital São Lucas da PUCRS)
Perez-Buira, Sandra (Hospital Universitario Fundación Jiménez Díaz)
Guerrero-Zotano, Ángel L. (Instituto Valenciano de Oncologia (IVO))
García-Sáenz, José A. (Instituto de Investigacion Sanitaria Hospital Clinico San Carlos)
Ayala, Francisco (Hospital General Universitario Gregorio Marañón)
Gómez, Henry L. (Universidad Ricardo Palma)
Rodríguez de la Borbolla, María (Hospital Universitario Virgen de Valme (Sevilla, Andalusia))
Baena-Cañada, Jose Manuel (Hospital Universitario Puerta del Mar (Cadis, Andalusia))
Calvo Martínez, Lourdes (Complejo Hospitalario Universitario de A Coruña)
Herranz, Jesús (GEICAM. Spanish Breast Cancer Group)
Rincon, Raul (GEICAM. Spanish Breast Cancer Group)
Caballero, Rosalía (GEICAM. Spanish Breast Cancer Group)
S. Ray, Partha (Onconostic Technologies. Inc. (OT))
Universitat Autònoma de Barcelona. Departament de Medicina

Data:	2025
Resum:	Purpose: In a prespecified GEICAM_CIBOMA trial (NCT00130533) correlative analysis, PAM50 non-basal-like breast cancer (non-BLBC) status distinguished patients with triple-negative breast cancer (TNBC) who are most likely to benefit from adjuvant capecitabine. The standardized forkhead box C1 (FOXC1) 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 patients with TNBC randomized to standard (neo)adjuvant chemotherapy followed by capecitabine versus observation were analyzed using the standardized FOXC1 IHC test to assess its BLBC/non-BLBC TNBC subtyping capacity as a distant relapse-free survival clinical outcome predictor of capecitabine benefit (exploratory endpoints: disease-free survival, overall survival, and recurrence-free survival). Results: A total of 705 (80. 5%) patients from the GEI-CAM_CIBOMA trial were evaluable for FOXC1 expression analysis, with balanced distribution between the trial's treat-ments. FOXC1 proportion/intensity (VFOXC1) score-based subtyping demonstrated a strong association [AUC ¼ 0. 87; 95% confidence interval (CI), 0. 84-0. 91] and agreement (κ index ¼ 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 distant relapse-free survival (HR, 0. 44; 95% CI, 0. 25-0. 76; P ¼ 0. 003). This predictive effect of VFOXC1 non-BLBC on capecitabine efficacy was further confirmed at disease-free survival (HR, 0. 47; 95% CI, 0. 28-0. 78; P ¼ 0. 003), overall survival (HR, 0. 48; 95% CI, 0. 24-0. 96; P ¼ 0. 038), and recurrence-free survival (HR, 0. 39; 95% CI, 0. 22-0. 72; P ¼ 0. 002). Conclusions: This ambispective GEICAM_CIBOMA translational analysis validated FOXC1-based basal-like/non-basal-like subtyping as a pragmatic alternative to PAM50 subtyping and independently predicted the benefit of adding capecitabine to standard (neo)adjuvant chemotherapy in TNBC.
Ajuts:	Instituto de Salud Carlos III PI24/00160
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, i la comunicació pública de l'obra, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original. No es permet la creació d'obres derivades.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Matèria:	Adult ; Aged ; Biomarkers, Tumor ; Capecitabine ; Chemotherapy, Adjuvant ; Disease-Free Survival ; Female ; Forkhead Transcription Factors ; Gene Expression Regulation, Neoplastic ; Humans ; Middle Aged ; Prognosis ; Treatment Outcome ; Triple Negative Breast Neoplasms
Publicat a:	Clinical cancer research, Vol. 31, Num. 17 (January 2025) , p. 3715-3724, ISSN 1557-3265

DOI: 10.1158/1078-0432.CCR-25-0338
PMID: 40569606

10 p, 9.4 MB

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