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

The standardized forkhead box C1 (FOXC1) IHC test has demonstrated strong reliability in classifying the BLBC subtype throughout TNBC cohorts.

标准化的叉头框C1（FOXC1）免疫组化（IHC）检测在对三阴性乳腺癌（TNBC）队列中的基底样乳腺癌（BLBC）亚型进行分类时，展现出了极高的可靠性。

This translational analysis aimed to evaluate the prognostic/predictive significance of BLBC classification by FOXC1 IHC in the phase III GEICAM_CIBOMA clinical trial.

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（IHC）对基底样乳腺癌（BLBC）分类的预后/预测意义。

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).

对随机接受标准（新）辅助化疗后使用卡培他滨与观察的三阴性乳腺癌（TNBC）患者的肿瘤组织进行了标准化FOXC1免疫组化（IHC）测试分析，以评估其作为卡培他滨获益的远处无复发生存临床结果预测指标的BLBC/非BLBC TNBC亚型分类能力（探索性终点：无病生存期、总生存期和无复发生存期）。

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.

在GEICAM_CIBOMA试验中，共有705名（占80.5%）患者可用于FOXC1表达分析，试验治疗的分布均衡。

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.

基于FOXC1比例/强度（VFOXC1）评分的亚型划分显示与PAM50分子亚型有很强的关联性[AUC = 0.87; 95%置信区间（CI），0.84-0.91]以及一致性（κ指数 = 0.43; P < 0.0001）。

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).

VFOXC1非BLBC型TNBC是卡培他滨对远处复发无病生存临床获益的一个显著独立预测因子（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).

VFOXC1非BLBC对卡培他滨疗效的预测效果在无病生存（HR，0.47；95% CI，0.28-0.78；P = 0.003）、总生存（HR，0.48；95% CI，0.24-0.96；P = 0.038）和无复发生存（HR，0.39；95% CI，0.22-0.72；P = 0.002）中得到了进一步确认。

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.

这项GEICAM_CIBOMA的回顾性和前瞻性转化分析验证了基于FOXC1的基底样/非基底样分型作为PAM50分型的一个实用替代方案，并独立预测了在三阴性乳腺癌中添加卡培他滨到标准（新）辅助化疗中的益处。