Exercise and inflammation in female survivors of breast cancer: systematic review and meta-analysis with secondary mediation analysis on body composition

Purpose
Inflammation plays a key role in breast cancer recurrence and mortality by promoting tumor progression. Exercise significantly reduces pro-inflammatory markers such as IL-6, TNF-α, and CRP, potentially reducing mortality risk. However, it is yet to be determined whether exercise-induced changes in body composition can modulate inflammatory biomarker responses in the breast cancer setting.

Methods
We conducted a secondary mediation analysis based on the findings from our previously published systematic review with meta-analysis. Randomized controlled trials examining the effects of exercise on IL-1β, IL-6, IL-8, IL-10, TNF-α, and CRP and body composition and anthropometry measures such as lean mass (LM), fat mass (FM), body weight and body mass index (BMI) were included. Random-effect meta-regression models were undertaken.

Results
Sixteen studies were included in the secondary analysis (n = 752). Increases in LM were significantly associated with reductions in IL-6 (p = 0.03) and there was a trend toward decreases in IL-8 (p = 0.05). In addition, there were non-significant trends suggesting that reductions in FM may be associated with decreases in IL-6 (p = 0.08) and TNF-α (p = 0.06), and that decreases in BMI may be linked to changes in IL-8 (p = 0.06).

Conclusions
Changes in body composition following exercise were not consistently associated with inflammatory biomarker responses in breast cancer survivors with only LM significantly associated with IL-6 while a trend in LM and FM existed for some other inflammatory markers. Although these findings do not provide conclusive evidence, they highlight a possible role of exercise-induced body composition changes in mediating inflammation. Further research is needed to clarify whether targeted exercise interventions that improve body composition can contribute to reducing inflammation and, ultimately, impact breast cancer progression, recurrence, and mortality.

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