The effect of renin angiotensin system on tamoxifen resistance.

Breast cancer is one of the most common forms of cancer observed in women and endogenous estrogens are thought to play a major role in its development. Tamoxifen is a selective estrogen receptor (ER) modulator which is widely used to treat and prevent breast cancer. Tamoxifen is an ER antagonist in the breast but an ER agonist in cardiovascular system (CVS) and some other tissues. Many patients experience resistance to tamoxifen. Several studies have indicated various mechanisms in tamoxifen resistance. Growth factors and their receptors, extracellular proteins, transcription factors, cell-cycle regulators, and signal-transduction molecules have been identified as being potentially involved in tamoxifen resistance. The aim of the present hypothesis is to provide evidences that may lead to this suggestion that renin-angiotensin system (RAS) may have a role in tamoxifen resistance. It has been established in numerous studies that RAS play a role in the progression of various cancers such as breast cancer. Besides, other studies have indicated that estrogen has an inhibitory effect on the RAS components levels in CVS and various tissues such as the adrenal and the pituitary. Therefore, it can be suggested that tamoxifen may increase RAS components levels in the breast tissue by its antagonistic effect on ER and causes resistance. Confirmation of this theory by experimental investigations may lead to this suggestion that combination of angiotensin-converting enzyme inhibitors or angiotensin receptor-1 blockers with tamoxifen may have a preventive effect on development of acquired tamoxifen resistance.