Comparative efficacy of exercise modes on inflammatory adipocytokines in patients with breast cancer: a systematic review with pairwise and network meta-analyses

Introduction and aim. Adipocytokines play a key role in the pathogenesis and progression of breast cancer and are increasingly recognized as potential therapeutic targets. The anti-inflammatory effects of regular exercise training are well-established, but its effects on inflammatory adipocytokines in individuals with breast cancer have not been elucidated. This systematic review and pairwise network meta-analyses aimed to (1) investigate the overall effects of exercise training on pro- and anti-inflammatory markers, and (2) compare the efficacy of different exercise modes using pairwise and network meta-analytic approaches. Methods . PubMed, Web of Science, and Scopus were systematically searched from inception to January 2025 using four groups of keywords, including “exercise”, “cytokine”, “breast cancer” and “randomized”. Randomized controlled trials investigating the effects of exercise training compared with a control (CON) or other modes of exercise on circulating IL-6, TNF-α, IL-10, CRP, leptin, and adiponectin in patients with breast cancer were included. Standardized mean differences (SMD) with 95% confidence intervals (CIs) were calculated using random-effects models for both pairwise and network meta-analyses. Results . Twenty-five studies involving 1,219 patients with breast cancer were. Compared with CON, exercise training led to significantly larger reductions in IL-6 [SMD: -0.39, p=0.02] and leptin [SMD: -0.77, p=0.01], and non-significant trends toward reductions in TNF-α [SMD: -0.30, p=0.05] and CRP [SMD: -0.47, p=0.07], but had no effect on IL-10 or adiponectin. In addition, high-intensity interval training (HIIT) reduced IL-6 [SMD: -1.08, p=0.01], with non-significant trends toward reduced TNF-α [SMD: -1.40, p=0.09] and raised IL-10 [SMD: 0.34, p=0.09]. Combined training (CT) decreased TNF-α [SMD: -0.65, p=0.006], and showed a trend towards lower leptin [SMD: -0.62, p=0.06]. No individual exercise mode impacted on in CRP or adiponectin compared with CON. Subgroup analyses suggested that intervention duration and patients’ clinical status influenced the magnitude of these effects. Conclusion . Exercise training appears to be effective in attenuating some markers of chronic low-grade inflammation by modulating key adipose-derived pro- and anti-inflammatory cytokines in patients with breast cancer, with HIIT and CT may confer superior benefits.