Figure 4.

Biological response of MCF-7 cells after 7 day treatment with premenopausal levels of estrone (E₁, 8nM) and estradiol (E₂, 4nM) found in plasma of premenopausal women during follicular phase of menstrual cycle [174] and tamoxifen metabolites 4OHT (6.3 nM), N-desmethyl-Tam (558 nM), tamoxifen (386 nM) and endoxifene (35.6 nM) at concentrations found in plasma of extensive metabolizers of tamoxifen [175]. As shown in the figure, combination of E₁/E₂ induce cell growth and treatment with combination of tamoxifen and its metabolites has minor effect on cells. Combination treatment of E₁/E₂ and tamoxifen metabolites does not ablate the proliferation of the cells. However, addition of another tamoxifen metabolite endoxifen at concentrations found in plasma of extensive metabolizers of tamoxifen (35.6 nM) produces almost complete inhibitory effect on cell growth. Treatment with combination of all tamoxifen metabolites (including endoxifen) does not have any major biological effect.