PURPOSE Although optimal treatment in early triple-negative breast cancer (TNBC) remains unclear, de-escalated chemotherapy appears to be an option in selected patients within this aggressive subtype. Previous studies have identified several pro-immune factors as prognostic markers in TNBC, but their predictive impact regarding different chemotherapy strategies is still controversial. EXPERIMENTAL DESIGN ADAPT-TN is a randomized neoadjuvant multicenter phase II trial in early patients with TNBC (n = 336) who were randomized to 12 weeks of nab-paclitaxel 125 mg/m2 + gemcitabine or carboplatin d 1,8 q3w. Omission of further (neo-) adjuvant chemotherapy was allowed only in patients with pathological complete response [pCR, primary endpoint (ypT0/is, ypN0)]. Secondary invasive/distant disease-free and overall survival (i/dDFS, OS) and translational research objectives included quantification of a predictive impact of markers regarding selection for chemotherapy de-escalation, measured by gene expression of 119 genes (including PAM50 subtype) by nCounter platform and stromal tumor-infiltrating lymphocytes (sTIL). RESULTS After 60 months of median follow-up, 12-week-pCR was favorably associated (HR, 0.24; P = 0.001) with 5y-iDFS of 90.6% versus 62.8%. No survival advantage of carboplatin use was observed, despite a higher pCR rate [HR, 1.04; 95% confidence interval (CI), 0.68-1.59]. Additional anthracycline-containing chemotherapy was not associated with a significant iDFS advantage in pCR patients (HR, 1.29; 95% CI, 0.41-4.02). Beyond pCR rate, nodal status and high sTILs were independently associated with better iDFS, dDFS, and OS by multivariable analysis. CONCLUSIONS Short de-escalated neoadjuvant taxane/platinum-based combination therapy appears to be a promising strategy in early TNBC for using pCR rate as an early decision point for further therapy (de-) escalation together with node-negative status and high sTILs. See related commentary by Sharma, p. 4840.

中文翻译：

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早期三阴性乳腺癌 (TNBC) 的降阶梯新辅助化疗：分子标志物的影响和 WSG-ADAPT-TN 试验的最终生存分析。

目的 尽管早期三阴性乳腺癌 (TNBC) 的最佳治疗仍不清楚，但降阶梯化疗似乎是这种侵袭性亚型中选定患者的一种选择。先前的研究已经确定了几种促免疫因素作为 TNBC 的预后标志物，但它们对不同化疗策略的预测影响仍存在争议。实验设计 ADAPT-TN 是一项随机新辅助多中心 II 期试验，在早期 TNBC 患者 (n = 336) 中随机接受为期 12 周的白蛋白结合型紫杉醇 125 mg/m2 + 吉西他滨或卡铂 d 1,8 q3w。只有病理学完全缓解 [pCR，主要终点 (ypT0/is，ypN0)] 的患者才允许省略进一步的（新）辅助化疗。继发性侵袭/远处无病生存和总生存（i/dDFS，OS）和转化研究目标包括量化标记物对化疗降阶梯选择的预测影响，通过 nCounter 平台和基质肿瘤浸润淋巴细胞（sTIL）的 119 个基因（包括 PAM50 亚型）的基因表达来测量。结果 在 60 个月的中位随访后，12 周 pCR 与 5y-iDFS 的相关性良好（HR，0.24；P = 0.001），分别为 90.6% 和 62.8%。尽管 pCR 率较高 [HR，1.04；95% 置信区间 (CI)，0.68-1.59]。在 pCR 患者中，额外的含蒽环类药物化疗与显着的 iDFS 优势无关（HR，1.29；95% CI，0.41-4.02）。通过多变量分析，除了 pCR 率之外，淋巴结状态和高 sTIL 与更好的 iDFS、dDFS 和 OS 独立相关。结论 短期降阶梯新辅助紫杉烷/铂类联合治疗似乎是早期 TNBC 的一种有前途的策略，可以将 pCR 率用作进一步治疗（降阶梯）以及淋巴结阴性状态和高 sTIL 的早期决策点。参见 Sharma 的相关评论，p. 4840。