Racial differences in tamoxifen metabolism

Abstract

PURPOSE: A recent study indicates that black women may have a higher risk/benefit ratio from tamoxifen than white women. Several reports in the literature indicate that racial differences in the risks/benefits from other pharmaceutical agents may be partially due to racial differences in drug metabolism. Thus, we explore the hypothesis that the racial difference in the tamoxifen risk/benefit ratio may be due, in part, to racial differences in tamoxifen metabolism.METHODS: We conducted a pilot study in which we recruited 6 white and 4 black breast cancer patients from the Baltimore, Maryland area. All patients were taking tamoxifen for at least 30 days. Each provided a blood sample that was used to measure tamoxifen metabolites by high performance liquid chromatography.RESULTS: Our results indicate that the black women had significantly higher levels of the tamoxifen metabolite, N-desmethyltamoxifen (N-DMT) than the white women (0.585 μg/ml vs 0.199 μg/ml, p < 0.05). There were no differences in the serum levels of tamoxifen in black and white women (0.809 vs 0.699, p > 0.1).CONCLUSIONS: These data suggest that both black and white breast cancer patients reach steady state tamoxifen levels, but that black women are more likely to metabolize tamoxifen to N-DMT or to maintain higher levels of N-DMT (i.e., less excretion of N-DMT) than white women. N-DMT is thought to be less effective in breast cancer treatment than tamoxifen. N-DMT also has been associated with excess proliferation in breast cancer cells. Thus, it is possible that the relatively high tamoxifen risk/benefit in black women occurs because tamoxifen is readily converted to N-DMT in black women, but not in white women. Although the data reported here are from a pilot study, it is important to note that significant racial differences in tamoxifen metabolism were observed with only a few participants. We urge other investigators to confirm these findings using a large population of breast cancer patients.