title: Are the effects of tamoxifen on the serum lipid profile modified by apolipoprotein E phenotypes?
abstract: BACKGROUND
  Tamoxifen has favorable effects on the serum lipid profile. It has been suggested that the apolipoprotein (Apo) E phenotype can influence serum lipid parameters; the ApoE allele 4 (ApoE4) is associated with higher total and low-density lipoprotein (LDL) cholesterol levels. The ApoE phenotype also affects lipid responses to diets or treatment with statins. However, the effect of tamoxifen on the lipid profile in different ApoE phenotypes is unknown.
  
  
  METHODS
  In the present study, we evaluated the effects of tamoxifen on the serum lipid profile in 11 ApoE4-positive postmenopausal women with breast cancer (phenotypes 3/4 and 4/4) compared with 33 ApoE4-negative women (phenotypes 3/2 and 3/3). Serum lipid parameters [high-density (HDL), LDL and total cholesterol, triglycerides, ApoAI, ApoB and lipoprotein (a)] were measured after an overnight fast before treatment and after 3 and 12 months. ApoE isoforms were determined by isoelectric focusing of delipidated very-low-density lipoproteins (VLDL).
  
  
  RESULTS
  During the follow-up period, serum levels of total and LDL cholesterol and ApoB decreased significantly in both groups, but no significant differences were found. Concentrations of serum HDL cholesterol were not significantly different between both groups. However, serum ApoAI levels increased significantly in ApoE4-negative subjects (p = 0.00005), but no significant changes in ApoE4-positive women were observed. Serum triglyceride levels increased by 23.2% (p < 0.05) in ApoE4-positive patients, but they did not change significantly in ApoE4-negative patients. The LDL/HDL cholesterol ratio decreased similarly in the two groups, but the ApoAI/ApoB ratio, which may be a better predictor of cardiovascular events, significantly changed in the ApoE4-negative subjects. Finally, the median level of Lp(a) decreased by 43.4% in the ApoE4-negative patients, whereas it did not change significantly in the ApoE4-positive group.
  
  
  CONCLUSIONS
  In postmenopausal Greek women with breast cancer, the levels of Lp(a) and triglycerides and the ApoAI/ApoB ratio respond more favorably to tamoxifen treatment in ApoE4-negative than in ApoE4-positive patients.
authors.affiliation: Department of Internal Medicine, Medical School, University of Ioannina, Ioannina, Greece.
authors.forename: Evagellos
authors.initials: E
authors.lastname: Liberopoulos
authors.forename: Sonia-Athena
authors.initials: SA
authors.lastname: Karabina
authors.forename: Alexandros
authors.initials: A
authors.lastname: Tselepis
authors.forename: Eleni
authors.initials: E
authors.lastname: Bairaktari
authors.forename: Costas
authors.initials: C
authors.lastname: Nicolaides
authors.forename: Nikolaos
authors.initials: N
authors.lastname: Pavlidis
authors.forename: Moses
authors.initials: M
authors.lastname: Elisaf
mesh_terms: D000368:Aged; D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology* / Q000627:therapeutic use; D001057:Apolipoproteins E / Q000235:genetics*; D001943:Breast Neoplasms / Q000097:blood* / Q000188:drug therapy; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D020847:Estrogen Receptor Modulators / Q000494:pharmacology* / Q000627:therapeutic use; D005260:Female; D006801:Humans; D008055:Lipids / Q000097:blood*; D008875:Middle Aged; D010641:Phenotype; D017698:Postmenopause / Q000097:blood*; D013629:Tamoxifen / Q000494:pharmacology* / Q000627:therapeutic use; D014280:Triglycerides / Q000097:blood
chemical_list: D018931:Antineoplastic Agents, Hormonal; D001057:Apolipoproteins E; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D020847:Estrogen Receptor Modulators; D008055:Lipids; D014280:Triglycerides; D013629:Tamoxifen