Exploring the effect of exercise training on breast cancer's pathologic response and tumor immune microenvironment after neoadjuvant chemotherapy

Abstract

Background: Pathological complete response (pCR) after neoadjuvant chemotherapy (NAC) and the percentage of tumor-infiltrating lymphocytes (TILs) are established prognostic biomarkers in early breast cancer (BC). While exercise training is effective as supportive care throughout the BC journey, its impact on the efficacy of NAC is unknown. This study aims to investigate the influence of a supervised exercise training program (SETP) on pCR and TILs in BC women undergoing NAC.

Methods: Retrospective exploratory analysis of the subgroup of BC patients treated with NAC included in a clinical trial randomizing to STEP and control arm. Endpoints were pCR, biopsy, and stromal TILs.

Results: Sixty-four participants were included, with a mean age of 50.3 ± 10.1 years, predominantly stage II and III disease (n = 58, 90.6%), HER2 + (n = 23, 35.9%), or triple-negative (n = 19, 29.7%) tumors. pCR was achieved in 56.7% and 55.9% in the STEP and control arm (p = 0.950). In the STEP arm, median TILs were 5.0 (0.0-80.0) and 5.0 (5.0-30.0), while in the control arm, 5.0 (0.0-90.0) and 0.0 (0.0-30.0) for biopsy and tumor site, respectively. The difference in TILs between arms was 0.04 (confidence interval (CI 95%) - 13.6, 13.7; p = 0.995) and - 4.3 (CI 95% - 11.5, 2.9; (p = 0.233) for biopsy and tumor site, respectively. No statistically significant difference was discerned between the groups concerning TILs of the biopsy. However, a marginally higher TIL level at the tumor site was associated with the SETP arm.

Conclusions: No differences were discerned within and between groups on both pCR and TILs, in possible relation to the exploratory nature of the analysis. Future adequately powered research is warranted.

Keywords: Breast cancer; Exercise; Neoadjuvant chemotherapy; Tumor-infiltrating lymphocytes.