%0 Journal Article
%T Associations between tamoxifen, estrogens, and FSH serum levels during steady state tamoxifen treatment of postmenopausal women with breast cancer
%A Jennifer Gjerde
%A Jščrgen Geisler
%A Steinar Lundgren
%A Dagfinn Ekse
%A Jan Varhaug
%A Gunnar Mellgren
%A Vidar M Steen
%A Ernst A Lien
%J BMC Cancer
%D 2010
%I BioMed Central
%R 10.1186/1471-2407-10-313
%X Tamoxifen and its metabolites were measured by liquid chromatography-tandem mass spectrometry. Estrogen and FSH levels were determined using a sensitive radio- and chemiluminescent immunoassay, respectively.We observed significant correlations between the serum concentrations of tamoxifen, N-dedimethyltamoxifen, and tamoxifen-N-oxide and estrogens (p < 0.05). The genotype predicted CYP2C19 activity influenced the levels of both tamoxifen metabolites and E1.We have shown an association between tamoxifen and its metabolites and estrogen serum levels. An impact of CYP2C19 predicted activity on tamoxifen, as well as estrogen kinetics may partly explain the observed association between tamoxifen and its metabolites and estrogen serum levels. Since the role of estrogen levels during tamoxifen therapy is still a matter of debate further prospective studies to examine the effect of tamoxifen and estrogen kinetics on treatment outcome are warranted.Estrogens play a key role in breast cancer development. The selective estrogen receptor modulator (SERM) tamoxifen has been used in breast cancer treatment and prevention. It may act as a full estrogen agonist, partial agonist or antagonist depending on the dose, species, sex or target organ [1]. Tamoxifen is regarded as a pro-drug since two of its metabolites, 4-hydroxytamoxifen (4OHtam) and 4-hydroxy-N-demethyltamoxifen (4OHNDtam, endoxifen), both have estrogen receptor affinity markedly exceeding that of tamoxifen itself [2,3]. The 4OHNDtam is considered the main active metabolite of tamoxifen, since it has 100-fold higher affinity for the estrogen receptor (ER) than tamoxifen and is 10-fold higher in serum levels than 4OHtam [4-7]. These potent metabolites are converted from tamoxifen through the cytochrome P450 (CYP) enzymes 2C19, 2D6, and 3A5. They are conjugated and deactivated through sulfotransferase (SULT) 1A1 [8,9] and UDP-glucuronyltransferases. The inter-individual variations of the activity of these enzymes due to ge
%U http://www.biomedcentral.com/1471-2407/10/313