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Estrogen Receptor Genotypes, Menopausal Status, and the Lipid Effects of Tamoxifen
Author(s) -
Ntukidem NI,
Nguyen AT,
Stearns V,
Rehman M,
Schott A,
Skaar T,
Jin Y,
Blanche P,
Li L,
Lemler S,
Hayden J,
Krauss RM,
Desta Z,
Flockhart DA,
Hayes DF
Publication year - 2008
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 - 10.1038/sj.clpt.6100343
Subject(s) - tamoxifen , medicine , endocrinology , estrogen receptor , breast cancer , selective estrogen receptor modulator , estrogen , estrogen receptor alpha , genotype , lipid profile , lipoprotein , cholesterol , biology , cancer , gene , genetics
Tamoxifen induces important changes in serum lipid profiles in some women; however, little information is available to predict which women will experience improved lipid profiles during tamoxifen therapy. As part of a multicenter prospective observational trial in 176 breast cancer patients, we tested the hypothesis that tamoxifen‐induced lipid changes were associated with genetic variants in candidate target genes ( CYP2D6, ESR1 , and ESR2 ). Tamoxifen lowered low‐density lipoprotein cholesterol ( P <0.0001) by 23.5 mg/dl (13.5–33.5 mg/dl) and increased triglycerides ( P =0.006). In postmenopausal women, the ESR1‐ Xba I and ESR2–02 genotypes were associated with tamoxifen‐induced changes in total cholesterol ( P =0.03; GG vs GA/AA) and triglycerides ( P =0.01; gene–dose effect), respectively. In premenopausal women, the ESR1‐ Xba I genotypes were associated with tamoxifen‐induced changes in triglycerides ( P =0.002; gene–dose effect) and high‐density lipoprotein ( P =0.004; gene–dose effect). Our results suggest that estrogen receptor genotyping may be useful in predicting which women would benefit more from tamoxifen. Clinical Pharmacology & Therapeutics (2008); 83 , 5, 702–710. doi: 10.1038/sj.clpt.6100343