Expression patterns and prognostic implications of tumor-infiltrating lymphocytes dynamics in early breast cancer patients receiving neoadjuvant therapy: A systematic review and meta-analysis.

Purpose: High levels of tumor-infiltrating lymphocytes (TILs) are associated with better outcomes in early breast cancer and higher pathological response rates to neoadjuvant chemotherapy especially in the triple-negative (TNBC) and HER2+ subtypes. However, the dynamic changes in TILs levels after neoadjuvant treatment (NAT) are less studied. This systematic review and meta-analysis aimed to investigate the patterns and role of TILs dynamics change in early breast cancer patients receiving NAT. Methods: Medline, Embase, Web of Science Core Collection and PubMed Central databases were searched for eligible studies. Data were extracted independently by two researchers and discordances were resolved by a third. Pooled TILs rates pre- & post-treatment (overall and per subtype), pooled rates of ΔTILs and direction of change after NAT as well as correlation of ΔTILs with survival outcomes were generated in the outcome analysis. Results: Of 2116 identified entries, 34 studies fulfilled the criteria and provided adequate data for the outcomes of interest. A decreased level of TILs was observed after NAT in paired samples across all subtypes. The effect of NAT on TILs was most prominent in TNBC subtype with a substantial change, either increase or decrease, in 79.3% (95% CI 61.7-92.6%) of the patients as well as in HER2+ disease (14.4% increased vs 46.2% decreased). An increase in ΔTILs in TNBC was associated with better disease-free/relapse-free survival in pooled analysis (univariate HR = 0.59, 95% CI: 0.37-0.95, p = 0.03). Conclusion: This meta-analysis illustrates the TILs dynamics during NAT for breast cancer and indicates prognostic implications of ΔTILs in TNBC. The potential clinical utility of the longitudinal assessment of TILs during neoadjuvant therapy warrants further validation.