{'fraction_non_alphanumeric': 0.029779058597502402, 'fraction_numerical': 0.012968299711815562, 'mean_word_length': 5.144542772861357, 'pattern_counts': {'":': 0, '<': 0, '<?xml version=': 0, '>': 0, 'https://': 0, 'lorem ipsum': 0, 'www.': 0, 'xml': 0}, 'pii_count': 0, 'substrings_counts': 0, 'word_list_counts': {'cursed_substrings.json': 0, 'profanity_word_list.json': 0, 'sexual_word_list.json': 0, 'zh_pornsignals.json': 0}}
Tamoxifen for the Prevention of Myocardial Infarction in Humans: Preclinical and Early Clinical Evidence

Received December 21, 2004; revision received May 18, 2005; accepted June 2, 2005. 

Tamoxifen is a member of the triphenylethylene class of drugs (Figure 1), originally derived from the estrogen-mimetic hydrocarbon stilbene.1 Like other members of the class (such as raloxifene, droloxifene, and toremifene), tamoxifen is dominantly an anti-estrogen: This is the mode of action that resulted in its widespread use for the treatment and prophylaxis of hormone-dependent cancers.2,3 More recently, however, it has become clear that its mode of action is more complex, with estrogen-like activities in some tissues and estrogen antagonist effects in others. This has led to the reclassification of this drug family as selective estrogen receptor modulators (or SERMs).4,5 



Figure 1. Structure of tamoxifen and the related SERM raloxifene. The common parental structure of the hydrocarbon stilbene is highlighted in bold.



Although the discovery6 of 2 isoforms of the estrogen receptor (one of the molecular targets of tamoxifen action), designated ER-α and ER-β, provided an attractive hypothesis to explain the differential effects of tamoxifen on different tissues, it remains difficult to rationalize the plethora of tamoxifen effects in terms of the expression patterns of estrogen receptor isoforms. In part, this may result from the use of terms such as “estrogen agonist activity” for physiological effects (such as lowering low-density lipoprotein [LDL] cholesterol), where tamoxifen mimics the effect of estrogen, even though it is unclear whether this effect of tamoxifen is mediated through the estrogen receptor or not.

More recently, tamoxifen and its analogues have been proposed for use in a wider range of diseases that might be affected by its pleiotropic effects,7 with particular focus on diseases where hormonal status is known to have an impact on incidence (such as osteoporosis and coronary heart disease [CHD]). Clinical trials with raloxifene (a …