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Size and Oxidative Susceptibility of Low-Density Lipoprotein Particles in Breast Cancer Patients with Tamoxifen-Induced Fatty Liver

Departments of Obstetrics and Gynecology (A.W., Y.Ok., T.F.), Radiology (Y.Og.), and Medicine (T.S.), Kochi Medical School, Kochi 783-8505, Japan

Address all correspondence and requests for reprints to: Akihiko Wakatsuki, M.D., Department of Obstetrics and Gynecology, Kochi Medical School, Oko cho, Nankoku, Kochi 783-8505, Japan. E-mail: . wakatuki{at}kochi-ms.ac.jpm

Abstract

The purpose of the present study was to investigate the effects of tamoxifen on the size and oxidative susceptibility of low-density lipoprotein (LDL) particles in breast cancer patients with tamoxifen-induced fatty liver. We investigated the following breast cancer patients: 13 receiving no tamoxifen (group A), 13 receiving tamoxifen 40 mg daily but without fatty liver (group B), and 13 receiving tamoxifen 40 mg daily with fatty liver (group C). Plasma lipids and diameter of LDL particles were measured. Susceptibility of LDL to oxidation was analyzed by incubation with CuSO₄ while monitoring conjugated diene formation and assaying thiobarbituric acid reactive substances (TBARS). Plasma total and LDL cholesterol concentrations in groups B and C were significantly lower than those in group A. In group C, concentrations of plasma triglyceride (TG) and TBARS were significantly greater, but LDL particle diameter and lag time for LDL oxidation were significantly smaller than those in groups A and B. Plasma TG concentrations correlated negatively with computed tomography ratio of liver to spleen (r = -0.76; P < 0.001). LDL particle diameter correlated negatively with plasma TG (r = -0.62; P < 0.001) and TBARS (r = -0.44; P < 0.01), but positively with LDL lag time (r = 0.47; P < 0.01). Tamoxifen-induced fatty liver in breast cancer patients may be atherogenic, via increased TG and consequent small, easily oxidized LDL particles.