Role of Estradiol, Progestins, Insulines and Adipocytokines in Breast Cancer Promotion in Post-Menopausal Women

Estrogens and artificial progestins used in hormone replacement therapy increase breast cancer risk. This seems to be due to a promoting and not initiating effect. A synergic effect of estradiol and hyperinsulinism has been shown. Insulin plays a role in the increase of breast cancer risk when associated with android obesity, sedentariness, type II diabetes, and high glycemic index food, alcohol and trans fatty acids intake. Natural menopause induces insulin resistance and does not induce a risk decrease. The role of insulin gives a new outlook on the influence of HRT in breast cancer promotion: estradiol alone, which improves insulin-sensitivity, does not increase breast cancer risk. Artificial progestins associated with estrogens increase the risk, whereas estrogens associated with progesterone do not. This could be due to the fact that artificial progestins increase insulin resistance, whereas natural progesterone does not. Adipose tissue, which is an endocrine gland, is insulin dependant. Breast cancer and its seriousness are correlated to adipocytokin circulating levels such as resistin, leptin, interleukin 1, adipocyte fatty acid-binding protein, and are inversely correlated to the level of adiponectin. Insulin could play a synergic role with sexual steroids by a direct effect and by increasing adipose tissue secretions.