Dashti SG, Simpson JA, Karahalios A, et al. - Given an increased risk of estrogen receptor (ER)-positive postmenopausal breast cancer is seen in relation to the presence of adiposity, researchers quantified mediating influences of fasting insulin and free estradiol in the adiposity and ER-positive postmenopausal breast cancer link. For this purpose, they utilized data from a case–cohort investigation of sex hormones and insulin signaling nested within the Melbourne Collaborative Cohort Study. There were 149 cases and 1,029 controls. The risk ratio of breast cancer was estimated to be 1.75 for women with BMI > 30 kg/m² vs women with BMI 18.5–25 kg/m². The percentage mediated effect through free estradiol was estimated to be 72%. For an indirect influence through insulin, no evidence was found. A crucial mediating role of circulating free estradiol in the adiposity–breast cancer link was suggested, however, circulating free estradiol did not explain all of the association.