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- Title
The impact of CYP2D6-predicted phenotype on tamoxifen treatment outcome in patients with metastatic breast cancer.
- Authors
Lammers, L. A.; Mathijssen, R. H. J.; van Gelder, T.; Bijl, M. J.; de Graan, A-J. M.; Seynaeve, C.; van Fessem, M. A.; Berns, E. M.; Vulto, A. G.; van Schaik, R. H. N.
- Abstract
<bold>Background: </bold>Cytochrome P450 2D6 (CYP2D6) has a crucial role in the metabolic conversion of tamoxifen into the active metabolite endoxifen. In this cohort study, the effect of CYP2D6-predicted phenotype, defined as the combined effect of CYP2D6 genetic variation and concomitant use of CYP2D6-inhibiting medication, on time to breast cancer progression (TTP) and overall survival (OS) in women who use tamoxifen for metastatic breast cancer (MBC) was examined.<bold>Methods: </bold>We selected patients treated with tamoxifen (40 mg per day) for hormone receptor-positive MBC from whom a blood sample for pharmacogenetic analysis (CYP2D6*3, *4, *5, *6, *10 and *41) was available. Patient charts (n=102) were reviewed to assess TTP and OS, and to determine whether CYP2D6 inhibitors were prescribed during tamoxifen treatment.<bold>Results: </bold>OS was significantly shorter in patients with a poor CYP2D6 metaboliser phenotype, compared with extensive metabolisers (HR=2.09; P=0.034; 95% CI: 1.06-4.12). Co-administration of CYP2D6 inhibitors alone was also associated with a worse OS (HR=3.55; P=0.002; 95% CI: 1.59-7.96) and TTP (HR=2.97; P=0.008; 95% CI: 1.33-6.67) compared with patients without CYP2D6 inhibitors.<bold>Conclusion: </bold>CYP2D6 phenotype is an important predictor of treatment outcome in women who are receiving tamoxifen for MBC. Co-administration of CYP2D6 inhibitors worsens treatment outcome of tamoxifen and should therefore be handled with care.
- Subjects
TAMOXIFEN; CANCER treatment; BREAST cancer patients; CYTOCHROME P-450; COHORT analysis
- Publication
British Journal of Cancer, 2010, Vol 103, Issue 6, p765
- ISSN
0007-0920
- Publication type
journal article
- DOI
10.1038/sj.bjc.6605800