Department of Pharmacy Administration, School of Business Administration, Shenyang Pharmaceutical University, Shenyang, China.
Department of Clinical Pharmacy, School of Life Sciences and Biopharmaceuticals, Shenyang Pharmaceutical University, Shenyang, China.
Breast. 2022 Dec;66:97-109. doi: 10.1016/j.breast.2022.10.001. Epub 2022 Oct 5.
This meta-analysis assessed the predictive and prognostic value of tumor infiltrating lymphocytes (TILs) in neoadjuvant chemotherapy (NACT) treated breast cancer and an optimal threshold for predicting pathologic complete response (pCR).
A systematic search of PubMed, EMBASE and Web of Science electronic databases was conducted to identify eligible studies published before April 2022. Either a fixed or random effects model was applied to estimate the pooled hazard ratio (HR) and odds ratio (OR) for prognosis and predictive values of TILs in breast cancer patients treated with NACT. The study is registered with PROSPERO (CRD42020221521).
A total of 29 published studies were eligible. Increased levels of TILs predicted response to NACT in HER2 positive breast cancer (OR = 2.54 95%CI, 1.50-4.29) and triple negative breast cancer (TNBC) (OR = 3.67, 95%CI, 1.93-6.97), but not for hormone receptor (HR) positive breast cancer (OR = 1.68, 95 %CI, 0.67-4.25). A threshold of 20% of H & E-stained TILs was associated with prediction of pCR in both HER2 positive breast cancer (P = 0.035) and TNBC (P = 0.001). Moreover, increased levels of TILs (either iTILs or sTILs) were associated with survival benefit in HER2-positive breast cancer and TNBC. However, an increased level of TILs was not a prognostic factor for survival in HR positive breast cancer (pooled HR = 0.64, 95%CI: 0.03-14.1, P = 0.78).
Increased levels of TILs were associated with increased rates of response to NACT and improved prognosis for the molecular subtypes of TNBC and HER2-positive breast cancer, but not for patients with HR positive breast cancer. A threshold of 20% TILs was the most powerful outcome prognosticator of pCR.
本荟萃分析评估了肿瘤浸润淋巴细胞（TILs）在新辅助化疗（NACT）治疗乳腺癌中的预测和预后价值，以及预测病理完全缓解（pCR）的最佳阈值。
对 PubMed、EMBASE 和 Web of Science 电子数据库进行系统检索，以确定截至 2022 年 4 月前发表的合格研究。应用固定或随机效应模型来估计 NACT 治疗的乳腺癌患者 TILs 的预后和预测价值的合并风险比（HR）和优势比（OR）。该研究已在 PROSPERO（CRD42020221521）注册。
共有 29 项已发表的研究符合条件。TILs 水平升高可预测 HER2 阳性乳腺癌（OR=2.54，95%CI，1.50-4.29）和三阴性乳腺癌（TNBC）（OR=3.67，95%CI，1.93-6.97）对 NACT 的反应，但不能预测激素受体（HR）阳性乳腺癌（OR=1.68，95%CI，0.67-4.25）。H&E 染色 TILs 阈值为 20%与 HER2 阳性乳腺癌（P=0.035）和 TNBC（P=0.001）的 pCR 预测相关。此外，TILs 水平（无论是 iTILs 还是 sTILs）升高与 HER2 阳性乳腺癌和 TNBC 的生存获益相关。然而，TILs 水平升高不是 HR 阳性乳腺癌生存的预后因素（合并 HR=0.64，95%CI：0.03-14.1，P=0.78）。
TILs 水平升高与 NACT 反应率增加和 TNBC 和 HER2 阳性乳腺癌分子亚型的预后改善相关，但与 HR 阳性乳腺癌患者无关。20% TILs 阈值是预测 pCR 最有力的预后指标。
