What clinicians need to know about antioestrogen resistance in breast cancer therapy

Tamoxifen is the drug most used for early breast cancer treatment in oestrogen receptor (ER) positive patients. Unfortunately, despite high ER tumour levels in a tumour, resistance to endocrine therapy, either de novo or acquired after prolonged treatment, can occur. In this review, we will try to summarise the postulated mechanisms of hormonal-resistance, namely, the role of co-regulators and the crosstalk between the HER-2, IGF-IR, Cox-2 and ER pathways. Other predictive markers of tamoxifen-resistance/response, such as cyclin E and UPA/PAI-1, are also discussed. (c) 2006 Elsevier Ltd. All rights reserved.