Endocrine resistance in breast cancer : gene expression profiling and modifications of the estrogen receptor

Endocrine treatment has had a groundbreaking contribution to the decline in breast cancer mortality. Tamoxifen inhibits the estrogen receptor (ER) and is part of the clinical management of breast cancer for more than 30 years and has been life saving for many breast cancer patients worldwide. However, still 30% of ER-positive breast cancer patients have no benefit from tamoxifen and endocrine resistance is still a major problem in daily clinical practice. Although tamoxifen resistance has been studied in in vitro models and in xenografts in mice for many years, this has not resulted in the clinical implementation of biomarkers that allow the prediction of tamoxifen resistance in ER-positive breast cancer patients. This thesis describes the discovery and validation of biomarkers that may predict response to tamoxifen. Basically two approaches are described: first, gene expression profiles of ER-positive breast tumors are determined, and second, modifications of the estrogen receptor are detected.