The impact of CYP2D6-predicted phenotype on tamoxifen treatment outcome in patients with metastatic breast cancer.
Br J Cancer
; 103(6): 765-71, 2010 Sep 07.
Article
en En
| MEDLINE
| ID: mdl-20700120
ABSTRACT
BACKGROUND:
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.METHODS:
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.RESULTS:
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.CONCLUSION:
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.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Tamoxifeno
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Neoplasias de la Mama
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Antineoplásicos Hormonales
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Citocromo P-450 CYP2D6
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Metástasis de la Neoplasia
Tipo de estudio:
Etiology_studies
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Incidence_studies
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Observational_studies
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Prognostic_studies
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Risk_factors_studies
Límite:
Adult
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Female
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Humans
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Middle aged
Idioma:
En
Revista:
Br J Cancer
Año:
2010
Tipo del documento:
Article
País de afiliación:
Países Bajos