J Cancer 2017; 8(18):3838-3848. doi:10.7150/jca.21051

Research Paper

The Predictive and Prognostic Role of Stromal Tumor-infiltrating Lymphocytes in HER2-positive Breast Cancer with Trastuzumab-based Treatment: a Meta-analysis and Systematic Review

Tao Xu1*, Bang-Shun He1*, Xiang-Xiang Liu1, Xiu-Xiu Hu1, 2, Kang Lin1, Yu-Qin Pan1, Hui-Ling Sun1, Hong-Xin Peng1, 2, Xiao-Xiang Chen1, 2, Shu-Kui Wang1✉

1. General Clinical Research Center, Nanjing First Hospital, Nanjing Medical University, Nanjing, China;
2. Medical college, Southeast University, Nanjing, China.
* These authors contributed equally to this work.

Abstract

Background Tumor-infiltrating lymphocytes (TILs) are white blood cells that have left the bloodstream and migrated into a tumor, involving in the prognosis of breast cancer (BC) patients. Published studies reported the value of TILs in patients with HER2-positive receiving trastuzumab-based treatment. However, the results obtained remain controversial. Here, we conducted this study to explore the predictive and prognostic role of TILs for HER2-positive BC patients receiving trastuzumab therapies.

Method To identify the related published studies, a comprehensive literature search dating up to July 2017 was performed in the databases of PubMed, PMC, Web of Science and China National Knowledge Infrastructure (CNKI) according to predefined selection criteria. The pathologic complete response (pCR) and survival outcome of patients were measured by odds ratio (OR) and hazard ratio (HR) with corresponding 95% confidence interval (95% CI), respectively. The association between TILs and trastuzumab benefit was analyzed by using STATA version 11.0.

Result Eleven eligible studies comprising 3228 patients were identified in the present study. The pooled results showed that high level of TILs was associated with a significantly improved pCR rate (OR = 1.32; 95% CI = 1.10-1.60) and longer survival (HR = 0.97; 95% CI = 0.96-0.99), particularly in the subgroups of retrospective study design and 10% INC cut-off value. Moreover, stratified analysis revealed that elevated TILs was a predictor of higher pCR rate in the Asian population and improved survival in the subgroups of Caucasian population and multivariate analysis.

Conclusion This meta-analysis indicated that the level of stromal TILs was an independent predictive and prognostic marker for better outcome in HER2-positive BC patients receiving trastuzumab-based treatment. High level of TILs was significantly associated with trastuzumab benefit.

Keywords: tumor-infiltrating lymphocytes, breast cancer, trastuzumab, pathologic complete response, survival.

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How to cite this article:
Xu T, He BS, Liu XX, Hu XX, Lin K, Pan YQ, Sun HL, Peng HX, Chen XX, Wang SK. The Predictive and Prognostic Role of Stromal Tumor-infiltrating Lymphocytes in HER2-positive Breast Cancer with Trastuzumab-based Treatment: a Meta-analysis and Systematic Review. J Cancer 2017; 8(18):3838-3848. doi:10.7150/jca.21051. Available from http://www.jcancer.org/v08p3838.htm