Selective oestrogen receptor modifiers (SERMs) and breast cancer therapy

Antioestrogen therapy is currently receiving renewed interest for several reasons. Tamoxifen was introduced in the treatment of metastatic breast cancer more than three decades ago. The drug significantly reduces long term mortality and also reduces the risk of contralateral tumours when administered in early breast cancer. Five years of tamoxifen is now standard in adjuvant endocrine therapy, and the drug is currently being evaluated for breast cancer prevention. Despite this, several aspects regarding the pharmacology of the drug are still unclear, and the scientific rationale for dose selection has recently been challenged. Several novel antioestrogen compounds, called selective oestrogen receptor modifiers (SERMs), express selective oestrogen agonistic or antagonistic properties depending on the organ or test system evaluated. Some of these drugs, like raloxifene, do not seem to promote the development of endometrial cancer, although they still have selected oestrogen-like beneficial effects. This paper reviews the pharmacologic and the pharmacokinetic aspects of the different SERMs with particular emphasis on their potential use in therapy and prevention of breast cancer.