Inflammation and Resistance Exercise in Breast Cancer Patients undergoing Adjuvant Radiotherapy

Abstract

PURPOSE: Exercise interventions have shown to reduce cancer-related fatigue and pain in breast cancer patients undergoing radiotherapy. Within a randomized controlled trial, we aimed to explore the mediating role of inflammatory parameters in the development of these symptoms during adjuvant radiotherapy and its mitigation by resistance exercise. METHODS: The randomized trial compared a 12-week progressive resistance exercise training (EX) with a 12-week relaxation control group. In 103 chemotherapy-naïve participants, interleukin-6 (IL-6) and interleukin-1 receptor antagonist (IL-1ra) were measured in serum samples collected before, at the end, and 6-weeks post-radiotherapy. Fatigue was assessed with the multidimensional Fatigue Assessment Questionnaire (FAQ), and pain with the EORTC QLQ-C30. Analysis of covariance (ANCOVA) models, partial correlations, Freedman-Schatzkin tests, and R2 effect-size measures for mediation were calculated. RESULTS: The ANCOVA models revealed a significant intervention effect on IL-6 (p=0.010) and the IL-6/IL-1ra ratio (p=0.018), characterized by a marked increase during radiotherapy among controls, but no significant change in EX. IL-1ra did not change significantly in either group (p=0.88). Increased IL-6 and IL-6/IL-1ra levels at the end of radiotherapy were significantly associated with increased physical fatigue and pain 6 weeks post-radiation. The effect of resistance exercise on physical fatigue was significantly mediated by IL-6 and IL-6/IL-1ra, but not by IL-1ra. IL-6 and IL-6/IL-1ra mediated between 15% and 24% of the variance of physical fatigue and pain explained by the intervention. CONCLUSIONS: This randomized controlled trial showed a significantly increased pro-inflammatory cytokine level after adjuvant radiotherapy in breast cancer patients. This effect was counteracted by progressive resistance exercise training. IL-6 and the IL-6/IL-1ra ratio appeared to mediate the beneficial effect of exercise on physical fatigue and pain, but only to a small extent. Supported by Intramural Funding of the National Center for Tumor Diseases (NCT), Heidelberg, Germany.