Figure 1

The effects of tamoxifen on human tissues. (a, b) Systemic administration of low tamoxifen (a) and topical administration of tamoxifen metabolites (b). Topical tamoxifen avoids high systemic exposure to 4-hydroxytamoxifen compared with standard oral tamoxifen, a 16- to 18-fold difference, thus reducing the risk of systemic side effects. Breast tissue concentrations seem to be sufficient to achieve inhibition of tumor cell proliferation to the same degree as that seen with the standard dose of oral tamoxifen (20 mg/day) but with much lower plasma levels. Tamoxifen has both good and bad effects on specific human tissues. Development of new approaches should maximize the good effects and minimize the bad effects.