FOXC1 Expression Predicts Capecitabine Efficacy in Patients with Triple-Negative Breast Cancer from the GEICAM_CIBOMA Trial

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)...

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Autores: Rojo, Federico|||0000-0001-9989-0290, Torrecillas, Laura, Ruiz-Borrego, Manuel, Bines, Jose, Torres, Roberto, de la Haba Rodríguez, Juan Rafael|||0000-0001-5111-1702, Llombart, Antonio, Barnadas i Molins, Agustí|||0000-0002-0429-1349, Bermejo, Begoña, Martin, Miguel, Taylor, Clive R., Barrios, Carlos, Perez-Buira, Sandra, Guerrero-Zotano, Ángel L., García-Sáenz, José A., Ayala, Francisco, Gómez, Henry L., Rodríguez de la Borbolla, María, Baena-Cañada, Jose Manuel, Calvo Martínez, Lourdes, Herranz, Jesús|||0000-0003-2469-357X, Rincon, Raul, Caballero, Rosalía, S. Ray, Partha
Tipo de documento: artigo
Data de publicação:2025
País:España
Recursos:Universitat Autònoma de Barcelona
Repositório:Dipòsit Digital de Documents de la UAB
Idioma:inglês
OAI Identifier:oai:dnet:uabarcelona_::06903938f441c2c5365926de8ea792e6
Acesso em linha:https://ddd.uab.cat/record/328735
https://dx.doi.org/urn:doi:10.1158/1078-0432.CCR-25-0338
Access Level:Acceso aberto
Palavra-chave: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
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network_name_str España
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spelling FOXC1 Expression Predicts Capecitabine Efficacy in Patients with Triple-Negative Breast Cancer from the GEICAM_CIBOMA TrialRojo, Federico|||0000-0001-9989-0290Torrecillas, LauraRuiz-Borrego, ManuelBines, JoseTorres, Robertode la Haba Rodríguez, Juan Rafael|||0000-0001-5111-1702Llombart, AntonioBarnadas i Molins, Agustí|||0000-0002-0429-1349Bermejo, BegoñaMartin, MiguelTaylor, Clive R.Barrios, CarlosPerez-Buira, SandraGuerrero-Zotano, Ángel L.García-Sáenz, José A.Ayala, FranciscoGómez, Henry L.Rodríguez de la Borbolla, MaríaBaena-Cañada, Jose ManuelCalvo Martínez, LourdesHerranz, Jesús|||0000-0003-2469-357XRincon, RaulCaballero, RosalíaS. Ray, ParthaAdultAgedBiomarkers, TumorCapecitabineChemotherapy, AdjuvantDisease-Free SurvivalFemaleForkhead Transcription FactorsGene Expression Regulation, NeoplasticHumansMiddle AgedPrognosisTreatment OutcomeTriple Negative Breast NeoplasmsPurpose: 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.Universitat Autònoma de Barcelona. Departament de Medicina 22025-01-0120252025-01-01Articlehttp://purl.org/coar/resource_type/c_6501VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttps://ddd.uab.cat/record/328735https://dx.doi.org/urn:doi:10.1158/1078-0432.CCR-25-0338reponame:Dipòsit Digital de Documents de la UABinstname:Universitat Autònoma de BarcelonaInglésengInstituto de Salud Carlos III https://doi.org/10.13039/501100004587 PI24/00160open accesshttp://purl.org/coar/access_right/c_abf2Aquest 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.https://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessoai:dnet:uabarcelona_::06903938f441c2c5365926de8ea792e62026-06-06T12:50:31Z
dc.title.none.fl_str_mv FOXC1 Expression Predicts Capecitabine Efficacy in Patients with Triple-Negative Breast Cancer from the GEICAM_CIBOMA Trial
title FOXC1 Expression Predicts Capecitabine Efficacy in Patients with Triple-Negative Breast Cancer from the GEICAM_CIBOMA Trial
spellingShingle FOXC1 Expression Predicts Capecitabine Efficacy in Patients with Triple-Negative Breast Cancer from the GEICAM_CIBOMA Trial
Rojo, Federico|||0000-0001-9989-0290
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
title_short FOXC1 Expression Predicts Capecitabine Efficacy in Patients with Triple-Negative Breast Cancer from the GEICAM_CIBOMA Trial
title_full FOXC1 Expression Predicts Capecitabine Efficacy in Patients with Triple-Negative Breast Cancer from the GEICAM_CIBOMA Trial
title_fullStr FOXC1 Expression Predicts Capecitabine Efficacy in Patients with Triple-Negative Breast Cancer from the GEICAM_CIBOMA Trial
title_full_unstemmed FOXC1 Expression Predicts Capecitabine Efficacy in Patients with Triple-Negative Breast Cancer from the GEICAM_CIBOMA Trial
title_sort FOXC1 Expression Predicts Capecitabine Efficacy in Patients with Triple-Negative Breast Cancer from the GEICAM_CIBOMA Trial
dc.creator.none.fl_str_mv Rojo, Federico|||0000-0001-9989-0290
Torrecillas, Laura
Ruiz-Borrego, Manuel
Bines, Jose
Torres, Roberto
de la Haba Rodríguez, Juan Rafael|||0000-0001-5111-1702
Llombart, Antonio
Barnadas i Molins, Agustí|||0000-0002-0429-1349
Bermejo, Begoña
Martin, Miguel
Taylor, Clive R.
Barrios, Carlos
Perez-Buira, Sandra
Guerrero-Zotano, Ángel L.
García-Sáenz, José A.
Ayala, Francisco
Gómez, Henry L.
Rodríguez de la Borbolla, María
Baena-Cañada, Jose Manuel
Calvo Martínez, Lourdes
Herranz, Jesús|||0000-0003-2469-357X
Rincon, Raul
Caballero, Rosalía
S. Ray, Partha
author Rojo, Federico|||0000-0001-9989-0290
author_facet Rojo, Federico|||0000-0001-9989-0290
Torrecillas, Laura
Ruiz-Borrego, Manuel
Bines, Jose
Torres, Roberto
de la Haba Rodríguez, Juan Rafael|||0000-0001-5111-1702
Llombart, Antonio
Barnadas i Molins, Agustí|||0000-0002-0429-1349
Bermejo, Begoña
Martin, Miguel
Taylor, Clive R.
Barrios, Carlos
Perez-Buira, Sandra
Guerrero-Zotano, Ángel L.
García-Sáenz, José A.
Ayala, Francisco
Gómez, Henry L.
Rodríguez de la Borbolla, María
Baena-Cañada, Jose Manuel
Calvo Martínez, Lourdes
Herranz, Jesús|||0000-0003-2469-357X
Rincon, Raul
Caballero, Rosalía
S. Ray, Partha
author_role author
author2 Torrecillas, Laura
Ruiz-Borrego, Manuel
Bines, Jose
Torres, Roberto
de la Haba Rodríguez, Juan Rafael|||0000-0001-5111-1702
Llombart, Antonio
Barnadas i Molins, Agustí|||0000-0002-0429-1349
Bermejo, Begoña
Martin, Miguel
Taylor, Clive R.
Barrios, Carlos
Perez-Buira, Sandra
Guerrero-Zotano, Ángel L.
García-Sáenz, José A.
Ayala, Francisco
Gómez, Henry L.
Rodríguez de la Borbolla, María
Baena-Cañada, Jose Manuel
Calvo Martínez, Lourdes
Herranz, Jesús|||0000-0003-2469-357X
Rincon, Raul
Caballero, Rosalía
S. Ray, Partha
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Universitat Autònoma de Barcelona. Departament de Medicina
dc.subject.none.fl_str_mv 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
topic 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
description 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.
publishDate 2025
dc.date.none.fl_str_mv 2
2025-01-01
2025
2025-01-01
dc.type.none.fl_str_mv Article
http://purl.org/coar/resource_type/c_6501
VoR
http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv https://ddd.uab.cat/record/328735
https://dx.doi.org/urn:doi:10.1158/1078-0432.CCR-25-0338
url https://ddd.uab.cat/record/328735
https://dx.doi.org/urn:doi:10.1158/1078-0432.CCR-25-0338
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.relation.none.fl_str_mv Instituto de Salud Carlos III https://doi.org/10.13039/501100004587 PI24/00160
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
https://creativecommons.org/licenses/by-nc-nd/4.0/
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
https://creativecommons.org/licenses/by-nc-nd/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.source.none.fl_str_mv reponame:Dipòsit Digital de Documents de la UAB
instname:Universitat Autònoma de Barcelona
instname_str Universitat Autònoma de Barcelona
reponame_str Dipòsit Digital de Documents de la UAB
collection Dipòsit Digital de Documents de la UAB
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,811543

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