Klin Onkol 2007; 20(6): 369-376.

Endocrine therapy is the most effective systematic treatment for patients with hormone-receptor positive breast cancer. Tamoxifen still represents the most commonly used endocrine treatment. Effi cacy of tamoxifen may be often limited by the onset of resistance. Knowledge on intracellular signal transduction pathways gained in the last years may explain possible mechanisms of tamoxifen
resistance. These mechanisms may include loss of expression and/or function of estrogen receptor (ER) or progesterone receptor (PR), alterations in co-regulatory proteins of ER, interferences in signal transduction pathways of growth factor receptors and ER, mutations in tumor suppressor gene p53, the signal transduction pathway PIK3 and alterations in pharmacokinetics of tamoxifen.