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Pharmacogenomics. 2011 Aug;12(8):1137-46. doi: 10.2217/pgs.11.54. Epub 2011 Aug 10.

The CYP2C19*2 genotype predicts tamoxifen treatment outcome in advanced breast cancer patients.

Author information

1
Erasmus MC Rotterdam, The Netherlands. r.vanschaik@erasmusmc.nl

Abstract

AIMS:

Tamoxifen is metabolized by cytochrome P450s, with an important role for CYP2D6. Recently, we demonstrated in 80 patients that CYP2C19*2 is associated with increased survival in breast cancer patients using tamoxifen. Here, we aimed to confirm this in a large group of 499 patients.

MATERIALS & METHODS:

A total of 499 estrogen receptor-positive primary breast tumor specimens of advanced disease patients treated with first-line tamoxifen were genotyped for CYP2C19*2 and *17 variant alleles, with primary end point time-to-treatment failure (TTF). Effects of CYP2C19, independent of treatment, were analyzed in 243 primary systematic untreated patients.

RESULTS:

CYP2C19*2 hetero- and homozygote patients combined showed significantly longer TTFs (hazard ratio [HR]: 0.72; 95% CI: 0.57-0.90; p = 0.004). In multivariate analysis, including CYP2D6*4 status, CYP2C19*2 remained independently associated with TTF (HR: 0.73; 95% CI: 0.58-0.91; p = 0.007). In untreated patients, the CYP2C19*17 allele was significantly associated with a longer disease-free interval (HR: 0.66; 95%CI: 0.46-0.95; p = 0.025).

CONCLUSION:

CYP2C19 genotyping is potentially important for tamoxifen therapy for advanced disease and for breast cancer prognosis.

PMID:
21830868
DOI:
10.2217/pgs.11.54
[Indexed for MEDLINE]

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