Prognostic and predictive value of tumor-infiltrating lymphocytes in breast cancer: a systematic review and meta-analysis

Clin Transl Oncol. 2016 May;18(5):497-506. doi: 10.1007/s12094-015-1391-y. Epub 2015 Oct 12.


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.

Result: 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.

Conclusion: 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.

Keywords: Breast cancer; Clinicopathological features; Prognosis; Tumor-infiltrating lymphocytes.

Publication types

  • Meta-Analysis
  • Review
  • Systematic Review

MeSH terms

  • Antineoplastic Combined Chemotherapy Protocols / adverse effects*
  • Biomarkers, Tumor / analysis*
  • Breast Neoplasms / drug therapy
  • Breast Neoplasms / immunology*
  • Breast Neoplasms / pathology
  • Female
  • Humans
  • Lymphocytes, Tumor-Infiltrating / immunology*
  • Neoadjuvant Therapy / adverse effects*
  • Neoplasm Staging
  • Prognosis
  • Survival Rate


  • Biomarkers, Tumor