ESR1 and obesity due to melanocortin 4 receptor deficiency: Moreover, the associated biochemical changes suggest that obesity and type 2 diabetes may promote breast cancer growth and progression, with a major role for aromatase-mediated extra-ovarian estrogen production, in ER-positive, largely postmenopausal, tumors, but estrogen-independent proinflammatory cytokine, adipokine and insulin effects in some ER-negative, predominantly premenopausal, breast cancers.