Predictive and prognostic role of tumour-infiltrating lymphocytes in breast cancer patients with different molecular subtypes: a meta-analysis.
Predictive and prognostic role of tumour-infiltrating lymphocytes in breast cancer patients with different molecular subtypes: a meta-analysis.
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DOI：
10.1186/s12885-020-07654-y
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发表时间：
2020-11-25
期刊：
影响因子：
3.8
通讯作者：
Jiang JY
中科院分区：
文献类型：
--
作者：
Gao ZH;Li CX;Liu M;Jiang JY
肿瘤浸润性淋巴细胞（TIL）是否在不同分子亚型的乳腺癌中发挥不同的作用仍不清楚。此外，它们在不同分子亚型乳腺癌中的预后和预测价值仍有争议。我们的荟萃分析的目的是通过总结所有相关研究进行多变量分析，以评估TIL在不同分子亚型乳腺癌中的预后和预测价值。全面检索了PubMed、Embase、EBSCO、ScienceDirect、科克伦数据库和Web of Science（截至2020年3月）。以风险比（HR）、优势比（OR）及其95%可信区间（CI）作为效应指标进行荟萃分析。采用随机效应模型。使用Stata软件版本15（2017）（StataCorp，学院站，TX，USA）进行统计分析。分析了33项研究，包括18，170名符合条件的乳腺癌患者。荟萃分析显示，在HER 2富集分子亚型患者中，TIL高表达与新辅助化疗后病理完全缓解（pCR）率增加显著相关。（OR = 1.137，95% CI [1.061 ~ 1.218]，p < 0.001）和三阴性乳腺癌（TNBC）亚型（OR = 1.120，95% CI [1.061 ~ 1.182]，p < 0.001）。但在管腔型乳腺癌患者中，TIL高表达与新辅助化疗后pCR率高无显著相关性（OR = 1.154，95% CI [0.789 ~ 1.690]，p = 0.460）。我们对总生存期（OS）和无病生存期（DFS）的HR进行了荟萃分析，以更深入地评估TIL在不同分子亚型乳腺癌中的预后价值。我们的荟萃分析证实，高TIL与HER 2富集分子亚型[HR = 0.940，95% CI（0.903 ~ 0.979），p = 0.003]和TNBC分子亚型[HR = 0.907，95% CI（0.862 ~ 0.954），p < 0.001]患者的DFS显著改善相关。然而，在乳腺癌的管腔分子亚型患者中，高TIL与显著更好的DFS无关[HR = 0.998，95%CI（0.977 ~ 1.019），p = 0.840]。此外，结果证实，在HER 2富集分子亚型[HR = 0.910，95% CI（0.866 ~ 0.957），p < 0.001]和TNBC分子亚型[HR = 0.869，95% CI（0.836 ~ 0.904），p < 0.001]患者中，高TIL与更好的OS显著相关。相反，总结的结果表明，在乳腺癌的管腔分子亚型患者中，高TIL与OS差显著相关[HR = 1.077，95% CI（1.016 ~ 1.141），p = 0.012]。我们的荟萃分析证实，高TIL与有利的生存期相关，并预测TNBC和HER 2富集分子亚型乳腺癌患者的pCR。
Whether tumour-infiltrating lymphocytes (TILs) play different roles in different molecular subtypes of breast cancer remains unknown. Additionally, their prognostic and predictive value in different molecular subtypes of breast cancer is still controversial. The aim of our meta-analysis was to assess the prognostic and predictive value of TILs in different molecular subtypes of breast cancer by summarizing all relevant studies performing multivariate analysis. PubMed, Embase, EBSCO, ScienceDirect, the Cochrane Database and Web of Science were comprehensively searched (until March 2020). Hazard ratios (HRs), odds ratios (ORs) and their 95% confidence intervals (CIs) were used as effect measures to perform our meta-analysis. A random effect model was used. Stata software, version 15 (2017) (StataCorp, College Station, TX, USA) was used to perform the statistical analysis. Thirty-three studies including 18,170 eligible breast cancer patients were analysed. The meta-analysis showed that high TIL expression was significantly associated with increased pathological complete response (pCR) rates after neoadjuvant chemotherapy in patients with the HER2-enriched molecular subtype (OR = 1.137, 95% CI [1.061 ~ 1.218], p < 0.001) and triple-negative breast cancer (TNBC) subtype (OR = 1.120, 95% CI [1.061 ~ 1.182], p < 0.001). However, high TIL expression was not significantly associated with high pCR rates after neoadjuvant chemotherapy in patients with the luminal molecular subtype of breast cancer (OR = 1.154, 95% CI [0.789 ~ 1.690], p = 0.460). We carried out a meta-analysis on the HRs of overall survival (OS) and disease-free survival (DFS) to assess the prognostic value of TILs in breast cancer with different molecular subtypes more deeply. Our meta-analysis confirmed that high TILs were associated with significantly improved DFS in patients with the HER2-enriched molecular subtype [HR = 0.940, 95% CI (0.903 ~ 0.979), p = 0.003] and TNBC molecular subtype [HR = 0.907, 95% CI (0.862 ~ 0.954), p < 0.001]. However, high TILs were not associated with significantly better DFS in patients with the luminal molecular subtype of breast cancer [HR = 0.998, 95% CI (0.977 ~ 1.019), p = 0.840]. Furthermore, the results confirmed that high TILs were significantly related to better OS in patients with the HER2-enriched molecular subtype [HR = 0.910, 95% CI (0.866 ~ 0.957), p < 0.001] and TNBC molecular subtype [HR = 0.869, 95% CI (0.836 ~ 0.904), p < 0.001]. Conversely, the summarized results indicated that high TILs were significantly associated with poor OS in patients with the luminal molecular subtype of breast cancer [HR = 1.077, 95% CI (1.016 ~ 1.141), p = 0.012]. Our meta-analysis confirms that high TILs are associated with favourable survival and predicts pCR in breast cancer patients with the TNBC and HER2-enriched molecular subtypes.
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