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Open Access Highly Accessed Research article

Associations between tamoxifen, estrogens, and FSH serum levels during steady state tamoxifen treatment of postmenopausal women with breast cancer

Jennifer Gjerde12, Jürgen Geisler345, Steinar Lundgren67, Dagfinn Ekse3, Jan Erik Varhaug89, Gunnar Mellgren12, Vidar M Steen1011 and Ernst A Lien12*

Author Affiliations

1 Hormone Laboratory, Haukeland University Hospital, Bergen, N-5021, Norway

2 Section for Endocrinology, Institute of Medicine, University of Bergen, Bergen, N-5021, Norway

3 Department of Oncology, Haukeland University Hospital, Bergen, N-5021, Norway

4 Section for Oncology, Institute of Medicine, University of Bergen, Bergen, N-5021, Norway; Faculty Division Akerhus University Hospital, University of Oslo, Oslo, N-0316, Norway

5 Section of Oncology, Department of Medicine, Akershus University Hospital, Lørenskog, N-1478, Norway

6 Department of Oncology, St. Olavs University Hospital, Trondheim, N-7006, Norway

7 Department of Cancer Research and Molecular Medicine, Faculty of Medicine, Norwegian University of Science and Technology, Trondheim, N-7006, Norway

8 Department of Surgery, Haukeland University Hospital, Bergen, N-5021, Norway

9 Department of Surgical Sciences, University of Bergen, Bergen, N-5021, Norway

10 Dr. E. Martens Research Group for Biological Psychiatry, Department of Clinical Medicine, University of Bergen, Bergen, N-5021, Norway

11 Center for Medical Genetics and Molecular Medicine, Haukeland University Hospital, Bergen, N-5021, Norway

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BMC Cancer 2010, 10:313  doi:10.1186/1471-2407-10-313

Published: 21 June 2010

Abstract

Background

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.