Patient Age Associates with Tumor-Infiltrating Lymphocytes Density in Breast Cancer

Abstract Background: Lymphocytes surrounding the cancer participate in tumor-related immune responses, and are called tumor-infiltrating lymphocytes (TILs). Several recent reports suggest TILs to index the tumor-microenvironment (TME), and predict the therapeutic effect of chemotherapy. However, only few studies have studied the relationship between age and TILs. Aging reduces host immunity, and we predict that it may also affect TILs. Thus, we hypothesized that older breast cancer (BC) patients may have low TILs density than younger BC patients. Here, we retrospectively analyzed the differences in TILs by age and the therapeutic effects of pre-operative chemotherapy (POC) in BC patients aged less than 45 years and more than 60 years.Methods: POC was administered to 356 patients. We confirmed and compared TILs density and therapeutic effects in patients aged 61 years (n=116). TIL density was evaluated using pre-treatment needle biopsy specimens. Definition and evaluation of TILs was based on the International TILs Working Group 2014.Results: Based on subtype, younger patients showed significantly higher pathological complete response rates than older patients with hormone receptor (HR)+ human epidermal growth factor receptor 2 (HER2)+ and HER2-enriched BC. In HR+HER2+BC, the objective response rate was significantly high in younger than in older patients. Further, a significant difference was observed for overall survival between these patients with triple-negative BC.Conclusions: Our study suggests that younger BC patients possess significantly high TILs density than older patients. These differences may influence the therapeutic efficacy in highly immunogenic subtypes.