ESR1 and breast cancer: Cross-talks between signaling pathways regulated by 17 beta-estradiol (E2) and insulin-like growth factor (IGF) (Bruning et al., 1992; Conover et al., 1992), strong mitogen for cancer cells (Beckwith and Yee, 2014), and actions through ER-signaling (Katzenellenbogen and Norman, 1990) are some possible mechanisms associated with the insulin effect on breast cancer.