Breast cancer can be treated in the majority of cases by blocking the action of the female sex hormones
(estrogens). Antiestrogens are drugs that block the action of estrogens in breast cancer cells. Several types of antiestrogens have been developed and appear to act by different mechanisms. As a consequence, it is sometimes possible to use a different type of molecule after development of resistance to the first therapeutic strategy. The goal of this application is to characterize the unique mechanism of action of the class of antiestrogens that inhibits estrogen signaling with greater efficacy, the full antiestrogens. We are presenting evidence for a novel mechanism of action of these molecules that contributes to their greater inhibition of estrogenic effects. This project will further clarify the mechanisms of action of these molecules and the reason for their activity against tumors that have become resistant to other types of hormonal therapies.