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CYP2C19 genotype predicts duration of response to tamoxifen in advanced breast cancer
Author(s) -
Schaik R.,
Teuling E.,
Meijer M.,
Heiden I.,
Fessem M.,
Vliet M.,
Staveren I.,
Look M.,
Klijn J.,
Foekens J.,
Lindemans J.,
Berns E.
Publication year - 2005
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1016/j.clpt.2004.11.088
Subject(s) - tamoxifen , cyp2c19 , genotype , breast cancer , medicine , oncology , cyp2d6 , estrogen , estrogen receptor , hazard ratio , allele , cancer , pharmacology , biology , cytochrome p450 , genetics , gene , metabolism , confidence interval
Background Resistance to anti‐estrogens is a major problem in breast cancer treatment. The anti‐estrogen tamoxifen is metabolized by cytochrome P450 enzymes. Genetic polymorphisms in these enzymes may alter tamoxifen metabolism and determine response to therapy. Methods Genomic DNA from 248 retrospectively collected estrogen receptor positive primary breast tumor specimens from patients with advanced disease were analysed for CYP2D6, 2B6, 2C9, 2C19 and 3A5 variant alleles. Results were compared to patient and tumor characteristics, outcome of response and time to tumor progression. Results No relation between patient or tumor characteristics and CYP450 genotype was observed, nor did CYP3A5, 2B6, 2C9 or 2D6 genotype correlate with treatment outcome. However, the CYP2C19*1/*1 genotype was significantly associated with a shorter time to tumor progression (hazard ratio 0.64; 95% C.I. 0.47–0.87; p=0.004). Conclusions Our data suggest that the duration of response to tamoxifen therapy is dependent on CYP2C19 genotype. Further studies are needed to investigate whether inhibition of CYP2C19 activity may result in a longer response to tamoxifen. Clinical Pharmacology & Therapeutics (2005) 77 , P23–P23; doi: 10.1016/j.clpt.2004.11.088