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dc.contributor.authorGjerde, Jenniferen_US
dc.contributor.authorGeisler, Jürgenen_US
dc.contributor.authorLundgren, Steinaren_US
dc.contributor.authorEkse, Dagfinnen_US
dc.contributor.authorVarhaug, Jan Eriken_US
dc.contributor.authorMellgren, Gunnaren_US
dc.contributor.authorSteen, Vidar Martinen_US
dc.contributor.authorLien, Ernst Asbjørnen_US
dc.PublishedBMC Cancer 10:313en_US
dc.description.abstractBackground The cytochrome P450 (CYP) enzymes 2C19, 2D6, and 3A5 are responsible for converting the selective estrogen receptor modulator (SERM), tamoxifen to its active metabolites 4-hydroxy-tamoxifen (4OHtam) and 4-hydroxy-N-demethyltamoxifen (4OHNDtam, endoxifen). Inter-individual variations of the activity of these enzymes due to polymorphisms may be predictors of outcome of breast cancer patients during tamoxifen treatment. Since tamoxifen and estrogens are both partly metabolized by these enzymes we hypothesize that a correlation between serum tamoxifen and estrogen levels exists, which in turn may interact with tamoxifen on treatment outcome. Here we examined relationships between the serum levels of tamoxifen, estrogens, follicle-stimulating hormone (FSH), and also determined the genotypes of CYP2C19, 2D6, 3A5, and SULT1A1 in 90 postmenopausal breast cancer patients. Methods 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. Results 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. Conclusions 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.en_US
dc.publisherBioMed Centraleng
dc.rightsAttribution CC BYeng
dc.titleAssociations between tamoxifen, estrogens, and FSH serum levels during steady state tamoxifen treatment of postmenopausal women with breast canceren_US
dc.typePeer reviewed
dc.typeJournal article
dc.rights.holderGjerde et al.
dc.rights.holderCopyright 2010 Gjerde et al; licensee BioMed Central Ltd.
dc.subject.nsiVDP::Medical disciplines: 700eng

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