ARTICLE ABSTRACTBackground: Insulin, IGF axis, adiponectin, and inflammatory markers are associated with breast cancer. Given that physical activity improves prognosis of breast cancer survivors, we investigated the effects of exercise on these markers as potential mediators between physical activity and breast cancer.Methods: PubMed, EMBASE, CENTRAL, CINAHL, and SportDiscus were searched up to December 3, 2015, to identify randomized controlled trials (RCT) that investigated the effect of exercise on insulin, IGF axis, and cytokines in breast cancer survivors. Weighted mean difference (WMD) was calculated using either fixed- or random-effects models on the basis of the heterogeneity of the studies.Results: A total of 18 studies involving 681 breast cancer survivors were included, and these numbers were reduced for individual biomarker analyses. We found that exercise significantly reduced fasting insulin levels [WMD, −3.46 μU/mL; 95% confidence interval (CI), −5.97 to −0.95; P = 0.007]. Furthermore, potentially meaningful but statistically nonsignificant changes were observed in insulin resistance (WMD, −0.73; 95% CI, −0.54 to 0.13; P = 0.23), adiponectin (WMD, 1.17 μg/mL; 95% CI, −0.87 to 3.20; P = 0.26), and C-reactive protein (WMD, −1.10 mg/L; 95% CI, −2.39 to 0.20; P = 0.10). Subgroup analyses showed that fasting insulin levels were significantly more impacted in studies in which intervention participants experienced a weight reduction (WMD, −7.10 μU/mL; 95% CI, −10.31 to −3.90; P < 0.001).Conclusions: Exercise reduces fasting insulin levels in breast cancer survivors. This may be due to exercise-induced reductions in body weight.Impact: Practitioners and clinicians may better help breast cancer prognosis be improved through exercise, anticipating physiological effects on cancer. Cancer Epidemiol Biomarkers Prev; 26(3); 355–65. ©2016 AACR.