Adiponectin increases insulin-like growth factor I-induced estradiol secretion [66], influences adjacent epithelial function by estrogen receptor(ER) -dependent and ER-independent mechanisms to reduce breast cancer risk [67] and E2 suppresses the adiponectin-regulated OPG/RANKL expression to inhibit osteoclastogenesis-related inflammation and bone resorption [68]. This evidence concerns the gene ESR1 and breast cancer.