The nuclear estrogen receptors (ER) are the major targets for endocrine treatment of hormone-dependent breast cancers. Hormone therapy blocked endogenous estrogen activation of ER, either by competitive inhibition of endogenous estrogens (selective estrogen receptor modulators - SERM or selective estrogen receptor down regulators - SERD) or by inhibition of estrogen synthesis (aromatase inhibitors) from adrenal androgens in post-menopausal women. The efficacy of these treatments has been shown on large series of breast cancer patients. However de novo or acquired resistance to treatment occurs. The better knowledge of the mechanism of action of such treatment may help to better understand them, and also for the determinism of adverse side effects of the different class of molecules.