Raloxifene

John   A.   Kellen

Abstract

Efforts to interfere with the initiation and promotion of breast and other cancers by endocrine manipulation are not new. It is of obvious benefit to cancer patients to administer substances that combine minimal general toxicity with maximal oestrogen inhibition. Raloxifene is a relatively recent addition to a group of compounds loosely designated as antioestrogens, which implies their ability to antagonize oestrogen effects via competitive binding to the various receptors. This is a reductionist simplification, since their effect varies and ranges from interaction with lipid transduction cascades, covalent binding to proteins and DNA, regulation of growth factors, erbB2, mdr1 and probably p53 expression, complexing with E-cadherin/catenin to active induction of apoptosis and many other effects on the genome. Also, the action of most antioestrogens is not solely antagonistic and different compounds do exert some agonistic effects in various tissues. Apart from some “pure” antioestrogens, the benzothiophene derivative Raloxifene has been found to combine a high degree of selective oestrogen suppression with several other desirable characteristics, such as reduction of bone demineralisation and antiatherogenic effects without endometrial stimulation. It is well tolerated, has been successfully tested as a chemopreventive agent for breast cancer in certain groups of the population and does not prevent ovulation in women with normal menstrual cycles. Certainly, Raloxifene is only another forerunner of upcoming “designer” oestrogen modulators, but it represents a welcome addition to the therapeutic choices available for the control of some menopausal problems as well as for the prevention and treatment of breast cancer, as outlined in the following brief review.

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