title: Tamoxifen therapy in breast cancer: do apolipoprotein E genotype and menopausal state affect plasma lipid changes induced by the drug?
abstract: OBJECTIVE
  This study examines the lipid profile change produced in response to tamoxifen (TAM) treatment, and its possible 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 increase 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 increased 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 genotype. Compared to premenopausal patients, postmenopausal breast cancer patients showed a more beneficial lipid profile change in response to treatment.
authors.affiliation: Department of Basic Biomedical Sciences, Faculty of Biomedical Sciences, Universidad Europea de Madrid, Madrid - Spain.
authors.forename: María
authors.initials: M
authors.lastname: Gaibar
authors.forename: Gerónimo
authors.initials: G
authors.lastname: Fernández
authors.forename: Alicia
authors.initials: A
authors.lastname: Romero-Lorca
authors.forename: Apolonia
authors.initials: A
authors.lastname: Novillo
authors.forename: Armando
authors.initials: A
authors.lastname: Tejerina
authors.forename: Fernando
authors.initials: F
authors.lastname: Bandrés
authors.forename: Ana
authors.initials: A
authors.lastname: Fernández-Santander
mesh_terms: D000328:Adult; D000368:Aged; D000483:Alleles; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use*; D001057:Apolipoproteins E / Q000097:blood / Q000235:genetics*; D001943:Breast Neoplasms / Q000097:blood* / Q000188:drug therapy* / Q000235:genetics; D008076:Cholesterol, HDL / Q000097:blood / Q000235:genetics; D008078:Cholesterol, LDL / Q000097:blood / Q000235:genetics; D015331:Cohort Studies; D005260:Female; D005838:Genotype; D006801:Humans; D050356:Lipid Metabolism / Q000187:drug effects*; D008055:Lipids / Q000097:blood* / Q000235:genetics; D008875:Middle Aged; D017698:Postmenopause / Q000097:blood / Q000235:genetics; D012189:Retrospective Studies; D013629:Tamoxifen / Q000627:therapeutic use*; D014280:Triglycerides / Q000097:blood / Q000235:genetics; D055815:Young Adult
chemical_list: D018931:Antineoplastic Agents, Hormonal; D001057:Apolipoproteins E; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D008055:Lipids; D014280:Triglycerides; D013629:Tamoxifen