title: Prognostic and predictive value of tumor-infiltrating lymphocytes in breast cancer: a systematic review and meta-analysis.
abstract: BACKGROUND
  Breast cancer is the most common invasive cancer to affect women in the world. Studies showed tumor-infiltrating lymphocytes can exhibit both beneficial and harmful effects on the biology and clinical outcome of breast cancer, the conclusion still remains incomplete. Here, we conducted a meta-analysis to evaluate the relationship between tumor-infiltrating lymphocytes and breast cancer.
  
  
  METHODS
  A comprehensive search strategy was used to search relevant literatures in PubMed and the ISI Web of Science. The correlation among TILs and breast cancer clinicopathological features and prognosis was analyzed by using Review Manager 5.3 and Stata 12.0.
  
  
  RESULTS
  Seventeen eligible studies consisting of 12,968 participants were included. We found that higher value of tumor-infiltrating lymphocytes had no relationship with breast cancer clinicopathological variables. Interestingly, it was correlated with response to neoadjuvant chemotherapy in majority (pooled RR 2.43, 95% CI 1.99-2.97). Moreover, higher value of total tumor-infiltrating lymphocytes (both intraepithelial and stromal) was associated with better prognosis (pooled HR 0.88, 95% CI 0.83-0.94), whereas some subtypes predicted a worse prognosis.
  
  
  CONCLUSIONS
  This meta-analysis indicated that high value of total TILs is not associated with breast cancer clinicopathological features, but can predict a favorable outcome for neoadjuvant chemotherapy in majority except for hormone receptor (-) subtype. And higher total TILs (both intraepithelial TILs and stromal TILs) may be the potential better prognostic indicators, while some subtypes like PD-1(+) TILs and Foxp3(+) TILs show a worse prognosis.
authors.affiliation: Cancer Institute (Key Laboratory of Cancer Prevention and Intervention, National Ministry of Education, Provincial Key Laboratory of Molecular Biology in Medical Sciences), The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310009, China.|Department of Oncology, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310009, China.
authors.forename: X
authors.initials: X
authors.lastname: Yu
authors.affiliation: Cancer Institute (Key Laboratory of Cancer Prevention and Intervention, National Ministry of Education, Provincial Key Laboratory of Molecular Biology in Medical Sciences), The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310009, China. zzg2011@zju.edu.cn.|Department of Oncology, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310009, China. zzg2011@zju.edu.cn.|Department of Gynecology, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310009, China. zzg2011@zju.edu.cn.
authors.forename: Z
authors.identifier: http://orcid.org/0000-0003-2380-1719
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Cancer Institute (Key Laboratory of Cancer Prevention and Intervention, National Ministry of Education, Provincial Key Laboratory of Molecular Biology in Medical Sciences), The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310009, China.
authors.forename: Z
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Cancer Institute (Key Laboratory of Cancer Prevention and Intervention, National Ministry of Education, Provincial Key Laboratory of Molecular Biology in Medical Sciences), The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310009, China.
authors.forename: P
authors.initials: P
authors.lastname: Wu
authors.affiliation: Cancer Institute (Key Laboratory of Cancer Prevention and Intervention, National Ministry of Education, Provincial Key Laboratory of Molecular Biology in Medical Sciences), The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310009, China.|Department of Oncology, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310009, China.
authors.forename: F
authors.initials: F
authors.lastname: Qiu
authors.affiliation: Cancer Institute (Key Laboratory of Cancer Prevention and Intervention, National Ministry of Education, Provincial Key Laboratory of Molecular Biology in Medical Sciences), The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310009, China.|Department of Oncology, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310009, China.
authors.forename: J
authors.initials: J
authors.lastname: Huang
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects*; D014408:Biomarkers, Tumor / Q000032:analysis*; D001943:Breast Neoplasms / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology; D005260:Female; D006801:Humans; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology*; D020360:Neoadjuvant Therapy / Q000009:adverse effects*; D009367:Neoplasm Staging; D011379:Prognosis; D015996:Survival Rate
chemical_list: D014408:Biomarkers, Tumor
keywords: Breast cancer; Clinicopathological features; Prognosis; Tumor-infiltrating lymphocytes