title: Tumor-infiltrating lymphocytes in breast cancer predict the response to chemotherapy and survival outcome: A meta-analysis.
abstract: Tumor-infiltrating lymphocytes (TILs) influence tumor prognosis and the chemotherapeutic response. Here, we quantified the clinical relevance of TILs, including the effect of TILs on lymphocyte subpopulations and assessed their consistency in breast cancer. We searched published literature from January 2000 to January 2016. The main parameters analyzed were pathological complete response (pCR) and survival outcome following chemotherapy in patients with breast cancer. Pooled odds ratio (OR) or relative risk (RR) values with 95% confidence intervals (CIs) were computed using random and fixed-effects models. Subgroup and heterogeneity analyses were also conducted. Twenty-three studies, which included 13,100 patients, met the inclusion criteria. The pooled results showed that TILs were associated with clinicopathological parameters of biologically aggressive phenotypes, such as high tumor grade or estrogen/progesterone receptor negativity, but they were not correlated with human epidermal growth factor receptor-2 expression. Moreover, a high TIL level was associated with a significantly improved pCR rate compared with a low TIL level (OR, 2.81; P < 0.001), particularly in the triple-negative breast cancer subtype (OR, 4.67; P < 0.001). An analysis of lymphocyte subpopulations showed that infiltration by CD8 lymphocytes, but not by CD4 lymphocytes and Foxp3 cells, was associated with a high pCR rate. Furthermore, a high TIL level was associated with significantly longer disease-free survival and overall survival. Our present meta-analysis indicates that an increased number of TILs predicted pCR to chemotherapy and improved survival. A high TIL level, characterized mainly by the infiltration of CD8 lymphocytes, is a strong predictive and prognostic factor.
authors.affiliation: Department of Oncology, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310009, China.
authors.forename: Ke
authors.initials: K
authors.lastname: Wang
authors.affiliation: School of Finance, Zhejiang University of Finance and Economics, Hangzhou, 310018, China.
authors.forename: Jianjun
authors.initials: J
authors.lastname: Xu
authors.affiliation: Department of Oncology, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310009, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Zhang
authors.affiliation: Department of Plastic Surgery, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310009, China.
authors.forename: Dan
authors.initials: D
authors.lastname: Xue
mesh_terms: D001943:Breast Neoplasms / Q000188:drug therapy* / Q000276:immunology* / Q000473:pathology; D017024:Chemotherapy, Adjuvant; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D016131:Lymphocyte Subsets / Q000276:immunology / Q000473:pathology; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology* / Q000473:pathology; D020360:Neoadjuvant Therapy; D011237:Predictive Value of Tests; D011379:Prognosis; D016019:Survival Analysis
keywords: breast cancer; lymphocyte infiltrates; meta-analysis; pathological complete response (pCR); prognosis