FOXC1表达可预测GEICAM_CIBOMA试验中三阴性乳腺癌患者的卡培他滨疗效。

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

作者信息

Rojo Federico, Taylor Clive R, Barrios Carlos, Torrecillas Laura, Ruiz-Borrego Manuel, Perez-Buira Sandra, Bines Jose, Guerrero-Zotano Angel, Garcia-Saenz Jose A, Torres Roberto, de la Haba-Rodriguez Juan, Ayala Francisco, Gomez Henry, Llombart Antonio, Rodriguez de la Borbolla Maria, Baena-Cañada Jose Manuel, Barnadas Agusti, Calvo Lourdes, Herranz Jesus, Rincon Raul, Caballero Rosalia, Bermejo Begoña, Ray Partha S, Martin Miguel

机构信息

GEICAM, Spanish Breast Cancer Group, Madrid, Spain.

Department of Pathology, Fundacion Jimenez Diaz University Hospital Health Research Institute (IIS-FJD, UAM)-CIBERONC, Madrid, Spain.

出版信息

Clin Cancer Res. 2025 Sep 2;31(17):3715-3724. doi: 10.1158/1078-0432.CCR-25-0338.

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

PMID:40569606

Abstract

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 GEICAM_CIBOMA trial were evaluable for FOXC1 expression analysis, with balanced distribution between the trial's treatments. FOXC1 proportion/intensity (VFOXC1) score-based subtyping demonstrated a strong association [AUC = 0.87; 95% confidence interval (CI), 0.84-0.91] and agreement (κ 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 distant relapse-free survival (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 disease-free survival (HR, 0.47; 95% CI, 0.28-0.78; P = 0.003), overall survival (HR, 0.48; 95% CI, 0.24-0.96; P = 0.038), and recurrence-free survival (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-like subtyping as a pragmatic alternative to PAM50 subtyping and independently predicted the benefit of adding capecitabine to standard (neo)adjuvant chemotherapy in TNBC.

摘要

目的

在一项预先指定的GEICAM_CIBOMA试验（NCT00130533）的相关性分析中，PAM50非基底样乳腺癌（非BLBC）状态可区分出最有可能从辅助性卡培他滨治疗中获益的三阴性乳腺癌（TNBC）患者。标准化的叉头框C1（FOXC1）免疫组化检测在整个TNBC队列的BLBC亚型分类中已显示出很强的可靠性。这项转化分析旨在评估在III期GEICAM_CIBOMA临床试验中，通过FOXC1免疫组化进行BLBC分类的预后/预测意义。

实验设计

对随机接受标准（新）辅助化疗后使用卡培他滨与观察治疗的TNBC患者的肿瘤组织，采用标准化的FOXC1免疫组化检测进行分析，以评估其作为卡培他滨获益的远处无复发生存临床结局预测指标的BLBC/非BLBC TNBC亚型分类能力（探索性终点：无病生存、总生存和无复发生存）。

结果

GEICAM_CIBOMA试验中共有705例（80.5%）患者可进行FOXC1表达分析，试验治疗组间分布均衡。基于FOXC1比例/强度（VFOXC1）评分的亚型分类与PAM50分子亚型分类显示出强相关性【曲线下面积（AUC）=0.87；95%置信区间（CI），0.84 - 0.91】和一致性（κ指数 = 0.43；P < 0.0001）。VFOXC1非BLBC TNBC亚型是卡培他滨治疗远处无复发生存临床获益的显著独立预测指标（风险比，0.44；95% CI，0.25 - 0.76；P = 0.003）。VFOXC1非BLBC对卡培他滨疗效的这种预测作用在无病生存（风险比，0.47；95% CI，0.28 - 0.78；P = 0.003）、总生存（风险比，0.48；95% CI，0.24 - 0.96；P = 0.038）和无复发生存（风险比，0.39；95% CI，0.22 - 0.72；P = 0.002）方面得到进一步证实。