INS and breast cancer: Hence, many possible mechanisms for the increase in risk have been proposed, including increased circulating levels of leptin and inflammatory cytokines (e.g., TNFα, IL-6, PAI1) and decreased adiponectin levels, as well as increased insulin/IGF signaling, elevated lipid levels, and, particularly in relation to breast cancer in postmenopausal women, an increase in aromatase expression in adipose tissue and a decrease in circulating sex hormone-binding globulin resulting (as mentioned earlier) in elevated bioavailable estradiol levels [1, 46, 47].