Low-grade inflammation and exercise training in women with breast cancer: A meta-analysis with meta-regression.

Background: Strong evidence has demonstrated that exercise training reduces breast cancer risk by 10-25%, and several biological mechanisms have been proposed to explain the positive modulation of inflammatory mediators associated with the tumor microenvironment. This study aims to determine the effects of exercise training on markers of low-grade inflammation in breast cancer survivors. Methods: A systematic literature review of randomized controlled trials (RCTs) evaluating the changes in inflammatory mediators in breast cancer survivors after exercise training was performed. The PubMed, Embase, Scopus and CENTRAL databases and other gray literature resources were searched without language restrictions from January 1990 to March 2014. Two investigators screened and identified the studies that met the inclusion criteria. An inverse of variance model of meta-analysis was performed using a random effects model in the presence of statistical heterogeneity (I2< 50%). Publication bias was evaluated using Egger’s test (p < 0.05). Results: Nine high-quality RCTs (n = 349) were ultimately included. Exercise training improved the serum concentrations of IL-6 (mean difference (MD) = -0.37, 95%CI -0.61 to -0.12), IL-2 (MD = 1.03, 95%CI 0.39 to 1.66), IL-8 (MD = -0.49, 95%CI -0.89 to-0.08) and TNF-α (MD = -0.48, 95%CI -0.96 to -0.003, p = 0.04). Conversely, no significant differences were found in the serum concentrations of C-reactive protein (CRP) or IL-10. There was no evidence of publication bias (p= 0.06). Conclusions: Exercise training positively modulates low-grade inflammation in women with breast cancer, impacting carcinogenic mechanisms and the tumor microenvironment. Additional RCTs are required to further elucidate the anti-inflammatory effects of exercise on breast cancer survivors.