Cytochrome P450 2D6 activity predicts discontinuation of tamoxifen therapy in breast cancer patients.
Pharmacogenomics J
; 9(4): 258-64, 2009 Aug.
Article
en En
| MEDLINE
| ID: mdl-19421167
ABSTRACT
The selective estrogen receptor modulator tamoxifen is routinely used for treatment and prevention of estrogen-receptor-positive breast cancer. Studies of tamoxifen adherence suggest that over half of patients discontinue treatment before the recommended 5 years. We hypothesized that polymorphisms in CYP2D6, the enzyme responsible for tamoxifen activation, predict for tamoxifen discontinuation. Tamoxifen-treated women (n=297) were genotyped for CYP2D6 variants and assigned a 'score' based on predicted allele activities from 0 (no activity) to 2 (high activity). Correlation between CYP2D6 score and discontinuation rates at 4 months was tested. We observed a strong nonlinear correlation between higher CYP2D6 score and increased rates of discontinuation (r(2)=0.935, P=0.018). These data suggest that presence of active CYP2D6 alleles may predict for higher likelihood of tamoxifen discontinuation. Therefore, patients who may be most likely to benefit from tamoxifen may paradoxically be most likely to discontinue treatment prematurely.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Tamoxifeno
/
Neoplasias de la Mama
/
Cooperación del Paciente
/
Antineoplásicos Hormonales
/
Citocromo P-450 CYP2D6
/
Moduladores Selectivos de los Receptores de Estrógeno
Tipo de estudio:
Clinical_trials
/
Observational_studies
/
Prognostic_studies
/
Risk_factors_studies
Límite:
Female
/
Humans
Idioma:
En
Revista:
Pharmacogenomics J
Asunto de la revista:
BIOLOGIA MOLECULAR
/
FARMACOLOGIA
Año:
2009
Tipo del documento:
Article
País de afiliación:
Estados Unidos