PII‐18

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 α[rs#2234693, (PvuII) and rs#9340799 (XbaI)] and β[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 ERα 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 ERα and ERβ genotypes, the subgroup with ER α 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 α 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. Clinical Pharmacology & Therapeutics (2005) 79 , P40–P40; doi: 10.1016/j.clpt.2005.12.143