Estrogen receptor genotypes, menopausal status, and the lipid effects of tamoxifen

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 23.5mg/dl (13.5-33.5 mg/dl) and increased triglycerides (P = 0.006). In postmenopausal women, the ESR1-Xbal 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-Xbal 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.