Role of estrogen receptor α transcriptional coregulators in tamoxifen resistance in breast cancer

Tamoxifen is the endocrine agent most commonly used at all stages of breast cancer. Estrogen receptor (ER) alpha, which belongs to the superfamily of nuclear receptors, has been used to identify breast cancer patients who are likely to respond to tamoxifen, but resistance nonetheless occurs in 30-50% of treated ER alpha-positive breast cancer patients. The antiproliferative activity of tamoxifen, relying primarily on its ability to compete with estrogen for the ER alpha ligand binding site in breast tumor tissue, hypotheses forwarded to explain treatment failure include: (1) the existence of a second estrogen receptor (ER beta), (2) an imbalance in estrogen biosynthesis and catabolism, (3) altered bioavailability of tamoxifen, (4) altered cellular trafficking of ER alpha, (5) non genomic effects of ERa, directly interacting with several signal transduction pathways, and (6) transcriptional dysregulation of ER alpha target genes, Which may involve both genomic (ERE alteration) and non genomic alterations.