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

Ron van Schaik, M (Marleen) de Kok, FCGJ Sweep, M van Vliet, M (Marianne) van Fessem, Marion Gelder, Caroline Seynaeve, Jan Lindemans, J Wesseling, LJ (Laura) van 't Veer, PN Span, H van Laarhoven, Stefan Sleijfer, John Foekens, SC Linn, Els Berns

Research output: Contribution to journalArticleAcademicpeer-review

40 Citations (Scopus)

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 ana-lysis, 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.
Original languageUndefined/Unknown
Pages (from-to)1137-1146
Number of pages10
JournalPharmacogenomics
Volume12
Issue number8
DOIs
Publication statusPublished - 2011

Cite this