1. ¹Department of Medicine, Indiana University, Indianapolis, Indiana, USA
2. ²Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, Maryland, USA
3. ³Department of Internal Medicine and Breast Oncology Program, Comprehensive Cancer Center, University of Michigan Health and Hospitals System, Ann Arbor, Michigan, USA
4. ⁴Children's Hospital Oakland Research Institute, Oakland, California, USA
5. ⁵Current address: Division of Hematology/Oncology, Department of Medicine, Ohio State University, Columbus, Ohio, USA.

Correspondence: DF Hayes, (hayesdf@umich.edu)

Received 20 December 2006; Accepted 6 July 2007; Published online 22 August 2007.

Abstract

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-XbaI 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-XbaI 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.