Background In patients with triple-negative breast cancer (TNBC), the extent of tumor-infiltrating lymphocytes (TILs) in the residual disease after neoadjuvant chemotherapy (NACT) is associated with better prognosis. Our objective was to develop a gene signature from pretreatment samples to predict the extent of TILs after NACT and then to test its prognostic value on survival. Patients and methods Using 99 pretreatment samples, we generated a four-gene signature associated with high post-NACT TILs. Prognostic value of the signature on distant relapse-free survival (DRFS) was first assessed on the training set (n = 99) and then on an independent validation set (n = 115). Results A four-gene signature combining the expression levels of HLF, CXCL13, SULT1E1, and GBP1 was developed in baseline samples to predict the extent of lymphocytic infiltration after NACT. In a multivariate analysis performed on the training set, this signature was associated with DRFS [hazard ratio (HR): 0.28, for a one-unit increase in the value of the four-gene signature, 95% confidence interval (CI): 0.13-0.63)]. In a multivariate analysis performed on an independent validation set, the four-gene signature was significantly associated with DRFS (HR: 0.17, 95% CI: 0.06-0.43). The four-gene signature added significant prognostic information when compared with the clinicopathologic pretreatment model (likelihood ratio test in the training set P = 0.004 and in the validation set P = 0.002). Conclusions A four-gene signature predicts high levels of TILs after anthracycline-containing NACT and outcome in patients with TNBC and adds prognostic information to a clinicopathological model at diagnosis.

中文翻译：

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三阴性乳腺癌患者新辅助化疗后可预测高肿瘤浸润淋巴细胞基因表达的基因特征。

背景在三阴性乳腺癌（TNBC）患者中，新辅助化疗（NACT）后残留疾病中肿瘤浸润淋巴细胞（TILs）的程度与更好的预后相关。我们的目标是从预处理样品中开发基因签名，以预测NACT后TIL的程度，然后测试其对生存的预后价值。患者和方法使用99个预处理样品，我们生成了与高NACT后TIL相关的四基因标记。首先在训练组（n = 99）上评估签名对远处无复发生存期（DRFS）的预后价值，然后在独立的验证组（n = 115）上进行评估。结果四基因签名结合了HLF，CXCL13，SULT1E1，在基线样本中开发出GBP1以预测NACT后淋巴细胞浸润的程度。在训练集上进行的多变量分析中，该特征与DRFS相关联[危险比（HR）：0.28，对于四基因特征的值增加一个单位，则95％置信区间（CI）：0.13 -0.63）]。在独立验证集上进行的多变量分析中，四基因签名与DRFS显着相关（HR：0.17，95％CI：0.06-0.43）。与临床病理预处理模型相比，四基因签名增加了重要的预后信息（训练集P = 0.004和验证集P = 0.002的似然比检验）。