Cited 33 times since 2011 (2.4 per year) source: EuropePMC Pharmacogenomics, Volume 12, Issue 8, 10 2 2011, Pages 1137-1146 The CYP2C19*2 genotype predicts tamoxifen treatment outcome in advanced breast cancer patients. van Schaik RH, Kok M, Sweep FC, van Vliet M, van Fessem M, Meijer-van Gelder ME, Seynaeve C, Lindemans J, Wesseling J, Van 't Veer LJ, Span PN, van Laarhoven H, Sleijfer S, Foekens JA, Linn SC, Berns EM
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.
