© 2013 Wichtig Editore - eISSN 1724-6008 Int J Biol Markers ( 2013; 4): e371-e376 28 - e371 ORIGINAL ARTICLE The role of the apolipoprotein E (ApoE) in lipid me- tabolism has been extensively investigated. It is well known that ApoE is a constituent of very low-density li- poproteins and high-density lipoproteins and acts as a ligand to hepatic receptors (5, 6). The 3 most common isoforms of the ApoE protein in humans are E2, E3 and E4, which are encoded by the corresponding alleles ε2, 3 and 4 (5, 6). The presence of some ApoE isoforms, such as ApoE4, determines faster chylomicron clearance and re- duced plasma TG levels, whereas the ApoE2 isoform has been associated with increased plasma TG levels due to its minimal receptor binding activity (7). Several studies have addressed whether the APOE genotype affects the link between serum lipids and breast cancer risk. For in- INTRODUCTION Tamoxifen (TAM) is widely used as an adjuvant in breast cancer (BC) treatment because of its antiestrogen effects. TAM therapy has been described as cardioprotec- tive due to its beneficial effects on lipoprotein metabo- lism, reducing plasma levels of total cholesterol (TC) and LDL-cholesterol (LDL-C) (1). In addition, TAM therapy has been linked to increased levels of apolipoprotein A-1 and reduced levels of apolipoprotein B-100, both considered reliable markers of cardiovascular disease (2). The use of TAM has also been related to elevated plasma triglyceride (TG) levels as an important adverse effect (3, 4). Tamoxifen therapy in breast cancer: do apolipoprotein E genotype and menopausal state affect plasma lipid changes induced by the drug? María Gaibar 1 , Gerónimo Fernández 1 , Alicia Romero-Lorca 1 , Apolonia Novillo 1 , Armando Tejerina 2 , Fernando Bandrés 2 , Ana Fernández Santander 1 1 Department of Basic Biomedical Sciences, Faculty of Biomedical Sciences, Universidad Europea de Madrid, Madrid - Spain 2 School of Advanced Studies, Fundación Tejerina, Madrid - Spain ABSTRACT Objective: This study examines the lipid profile change produced in response to tamoxifen (TAM) treatment, and its pos- sible relationship with both apolipoprotein E genotype and menopausal state in patients with breast cancer. Methods: Blood samples were collected from 86 Spanish women with breast cancer before initiating TAM treatment and in the following 6, 12 and 18 months of treatment. Plasma lipid levels (total cholesterol, triglycerides, HDL-cholesterol and LDL-cholesterol) were determined using an automatic analyzer. Genotypes for apolipoprotein E (ApoE) were identified by PCR-RFLP using the HhaI enzyme. Results: In all patients, significant reductions in total cholesterol and LDL-cholesterol concentrations and a significant in- crease in triglyceride concentrations were observed after 6, 12, and 18 months of TAM treatment compared to baseline (p<0.01 for each time point). In the subset of APOE4-negative patients, triglyceride concentrations also significantly in- creased after 6, 12, and 18 months of treatment (p=0.019, p=0.045, p=0.001, respectively), while APOE4-positive patients showed no significant lipid changes at 12 and 18 months. However, after 18 months of TAM treatment the overall triglyceride concentrations had risen by 24.75% in APOE4-negative patients vs 29.9% in APOE4-positive patients. In postmenopausal women, significant reductions in total cholesterol, LDL-cholesterol and LDL/HDL ratios were observed at each time point (p<0.020 for each). Conclusions: TAM treatment induced similar plasma triglyceride increases in patients with positive or negative APOE geno- type. Compared to premenopausal patients, postmenopausal breast cancer patients showed a more beneficial lipid profile change in response to treatment. Key words: Breast cancer, Apolipoprotein E, Tamoxifen, Lipid profile, Hypertriglyceridemia Received: April 10, 2013; Accepted: June 7, 2013 DOI: 10.5301/JBM.5000037 FOR PERSONAL USE ONLY