Mechanisms of tamoxifen resistance in the treatment of advanced breast cancer.

Multiple mechanisms may render breast cancer cells resistant to treatment with the antiestrogen tamoxifen. This review describes changes in the estrogen receptor (ER) signaling pathway which may lead to tamoxifen resistance: change in uptake or metabolism of tamoxifen, loss of expression of ER, decreased expression of ER, expression of mutant or variant forms of ER, intact ER but loss of cofactors, ligand-independent ER activation, modification of the estrogen response element, altered post-receptor events. Non-ER related alterations are also mentioned.