PURPOSE The present study evaluated tumor-infiltrating lymphocytes (TILs) based on standardized scoring method and investigated its predictive value for axillary pathologic complete response (apCR) and prognostic significance for event-free survival (EFS) in neoadjuvant-treated HER2-positive breast cancer with initially biopsy-proven nodal metastasis. METHODS We assessed TILs in a total of 187 pretherapeutic core biopsies of primary tumors. Receiver operating characteristic curve analysis was conducted to calculate the optimal cut-off point of TILs in discriminating axillary pathologic response. The associations of TILs with apCR or EFS were investigated by univariate and multivariate analyses. RESULTS Receiver operating characteristic curve analysis identified a 10% cut-off point of TILs that optimally discriminated apCR from non-apCR (P < 0.001). High TILs were determined as TILs ≥ 10%, and tumor with TILs < 10% was defined as lymphocyte-depleted breast cancer (LDBC). The apCR rate of the entire cohort was 66.3% (124/187). Tumors with high TILs had a significantly higher apCR rate compared with LDBC (78.5% vs. 43.9%; P < 0.001). High TILs (P < 0.001), breast pathologic complete response (P = 0.006), and negative status of hormone receptor (P = 0.021) were independent predictors for apCR. High TILs were a markedly powerful predictor with an odds ratio of 4.01 (P < 0.001). EFS was significantly better among patients with high TILs than among those with LDBC (P < 0.001). Univariate and multivariate analyses indicated that high TILs (P = 0.019) and apCR (P = 0.013) were independent predictors for favorable EFS. CONCLUSIONS TILs have predictive value for apCR and prognostic significance for EFS in initially node-positive and HER2-positive breast cancer treated with neoadjuvant therapy. LDBC (TILs < 10%) has a significantly unfavorable impact on apCR rate and EFS.

中文翻译：

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在接受新辅助治疗的 HER2 阳性和活检证实的淋巴结阳性乳腺癌中，肿瘤浸润淋巴细胞有利于预测腋窝病理反应和无事件生存率。

目的本研究基于标准化评分方法评估肿瘤浸润淋巴细胞 (TIL) 并研究其对新辅助治疗的 HER2 阳性乳腺癌腋窝病理完全缓解 (apCR) 的预测价值和无事件生存 (EFS) 的预后意义最初活检证实有淋巴结转移。方法 我们评估了总共 187 个原发性肿瘤的治疗前核心活检中的 TIL。进行接受者操作特征曲线分析以计算TILs区分腋窝病理反应的最佳截止点。通过单变量和多变量分析研究了 TIL 与 apCR 或 EFS 的关联。结果 接受者操作特征曲线分析确定了 TIL 的 10% 截止点，可以最佳地区分 apCR 和非 apCR（P < 0. 001）。高 TIL 被确定为 TIL ≥ 10%，TIL < 10% 的肿瘤被定义为淋巴细胞耗竭型乳腺癌 (LDBC)。整个队列的 apCR 率为 66.3% (124/187)。与 LDBC 相比，具有高 TIL 的肿瘤具有显着更高的 apCR 率（78.5% 对 43.9%；P < 0.001）。高 TIL（P < 0.001）、乳腺病理完全缓解（P = 0.006）和激素受体阴性（P = 0.021）是 apCR 的独立预测因子。高 TIL 是一个非常强大的预测因子，优势比为 4.01（P < 0.001）。高 TIL 患者的 EFS 显着优于 LDBC 患者（P < 0.001）。单变量和多变量分析表明，高 TIL（P = 0.019）和 apCR（P = 0.013）是有利 EFS 的独立预测因子。结论 TILs 对 apCR 具有预测价值，对接受新辅助治疗的初始淋巴结阳性和 HER2 阳性乳腺癌的 EFS 具有预后意义。LDBC（TIL < 10%）对 apCR 率和 EFS 有显着不利影响。