¹Indiana University, University of Michigan, Indianapolis, IN

Abstract

Background: Breast cancer and non-tumoral responses during tamoxifen treatment are variable; and this variability may be genetic.

Methods: We prospectively followed 185 breast cancer patients on tamoxifen therapy. Serum lipid analyses were performed in Clinical Laboratories at baseline and after 4 months of treatment. Genetic variants in the estrogen receptors [rs#2234693, (PvuII) and rs#9340799 (XbaI)] and [rs#1256049 (ESR2-01) and rs#4986938(ESR-02)] were analyzed.

Results: Tamoxifen significantly lowered cholesterol (-24.2 mg/dl) and LDL (-26.9mg/dl) compared to baseline. Women with the ER PvuII CC allele had a 2-fold greater decrease in total cholesterol when compared to women with CT/TT alleles (P=0.01). The premenopausal women with the AA/AG alleles of ER XbaI had a lower baseline total (204 vs. 244 mg/dl; P=0.012,) and LDL cholesterol (116 vs.150mg/d; p=0.0l) compared to women with the GG alleles. There was no association between baseline cholesterol and the XbaI polymorphism in postmenopausal women. In a multivariate analysis, grouping the subjects according to their combined ER and ER genotypes, the subgroup with ER PvuII CC and any ESR2-02 allele combination had the greatest reduction in total cholesterol concentration in response to tamoxifen when compared to women with ER CT/TT and any ESR2-02 (P=0.0032).

Conclusions: Estrogen receptor genotypes are associated with baseline cholesterol and the response of serum cholesterol to tamoxifen treatment in breast cancer.