Endocrine therapy is a major modality of treatment in breast cancer.Current selection for the treatment is based on presence of active estrogen receptors (ER) in the tumor: most of ER-positive tumors slow their growth in response to estrogen deprivation.However, some tumors fail to respond despite the possession of estrogen receptors.Moreover,many patients, who initially respond to treatment, develop resistance later.Multiple mechanisms have been suggested to explain endocrine resistance including individual variations in tamoxifen metabolism, aberrations in ER, mutations in cell cycle machinery, estrogen-independent phosphorilation of ER, activation of co-factors and growth-factor signaling.Most of these mechanisms have been suggested and studied in experimental models.At the same time,studies reporting molecular profiles in clinical biopsies usually analyze all resistant tumors as a single entity, contrasting them to the responsive ones.