A mediation analysis of obesity and adiponectin association with postmenopausal breast cancer risk: a nested cohort study in the IBIS-II Prevention Trial

Abstract Purpose Obesity is a risk factor for postmenopausal breast cancer and evidence supports the pivotal role of adiponectin in the association between obesity and breast cancer. We aimed to investigate whether the effect of baseline body mass index (BMI) on postmenopausal breast cancer risk was mediated by adiponectin or other circulating biomarkers. Methods We measured adiponectin, leptin, IGF-I, IGFBP-1, high-sensitivity C-reactive protein, glycemia, insulin, HOMA-IR index, and SHBG in baseline and 12-month serum samples from 123 cases and 302 matched controls in the placebo arm of the IBIS-II Prevention trial. We conducted the main mediation analysis considering BMI at baseline as an exposure and the increase in adiponectin at 12 months as a mediator after adjustment for the Tyrer-Cuzick score and the use of lipid-lowering medications and supplements. Results The 12-month increase in adiponectin levels was significantly associated with a 40% decrease in the risk of breast cancer [hazard ratio (HR), 0.60; 95% confidence interval (95% CI), 0.36-1.00]. The estimate of the association of BMI was low, indicating only a 5% increase in breast cancer risk (HR, 1.05; 95% CI, 1.00-1.09). The increase in adiponectin levels at 12 months did not mediate the effect of BMI on breast cancer risk (HR, 1.00; 95% CI, 0.98–1.02). Conclusion Mediation analysis indicated an independent role of adiponectin in postmenopausal breast cancer risk. Raising adiponectin levels might be an attractive target for postmenopausal breast cancer prevention.