Abstract P1-13-13: Association between the serum concentrations of tamoxifen and its metabolites and age during steady state breast cancer treatment

Abstract

Abstract It has been suggested that the concentrations of tamoxifen and its demethylated metabolites increase with age. Here, we measured the serum concentrations of the active tamoxifen metabolites, 4OHtamoxifen (4OHtam), 4OHNdesmethyltamoxifen (4OHNDtam, Endoxifen), tamoxifen and its demethylated metabolites. Their relations to age were examined. 151 breast estrogen receptor and/or progesterone receptor positive cancer patients were included. Tamoxifen and its metabolites were measured by liquid chromatography-tandem mass spectrometry. Their serum concentrations were related to the age of the patients. The concentrations of 4OHNDtam, tamoxifen, NDtam (N-desmethyltamoxifen), and NDDtam (N-desdimethyltamoxifen) were positively correlated to age (n = 151, P = 0.017, 0.045, 0.011, and 0.001 respectively). Up to tenfold inter-patient variation in the serum concentrations was observed. The median (inter-patient range) of the concentrations 4OHNDtam in the age groups 30-49, 50-69 and >69 years were 44 (65) ng/ml, 51 (116) ng/ml, and 54 (159) ng/ml, respectively. We conclude that the serum concentrations of 4OHNDtam (endoxifen), tamoxifen and its demethylated metabolites increase with age during steady state tamoxifen treatment. The observed high inter-patient range in serum concentrations of tamoxifen and its metabolites, especially in the highest age group, suggest that use of therapeutic monitoring of tamoxifen and its metabolites is warranted. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P1-13-13.