title: Administration of long-term tamoxifen therapy modifies the plasma lipoprotein-lipid concentration and lipid transfer protein I activity in postmenopausal women with breast cancer.
abstract: Tamoxifen remains one of the most effective agents in the treatment of breast cancer. However, the development of persistent side effects from chronic administration of tamoxifen remains a concern. The objective of this project was to investigate the effect of long-term tamoxifen therapy (2 years) on the plasma lipoprotein concentration and lipid transfer activity in postmenopausal women diagnosed with breast cancer. Two distinct populations of breast cancer patients were recruited for this study: postmenopausal women diagnosed with breast cancer that have never been on tamoxifen and postmenopausal women diagnosed with breast cancer that have been on tamoxifen (20 mg once daily) for 2 years (n = 18 each group). Blood was collected for total and lipoprotein cholesterol (C) and triglyceride (TG) analysis by established enzymatic assays prior to and 2 years following the initial tamoxifen dose. To determine the effect of tamoxifen administration on lipid transfer between lipoprotein fractions, lipid transfer protein (LTP I) activity was measured. A significant decrease in total and low-density lipoprotein (LDL) cholesterol levels and a moderate increase in high-density lipoprotein (HDL) triglyceride levels were observed in plasma samples from postmenopausal women with breast cancer who were administered tamoxifen for 2 years. No significant differences in total and lipoprotein C and TG plasma levels were observed in samples from women with breast cancer that never received tamoxifen. LTP I activity was significantly decreased in patients receiving tamoxifen compared to patients who never received tamoxifen. These specific tamoxifen-induced effects may be important for a number of reasons. Although the apparent decrease in total C and LDL-C levels are favorable for reducing the risk of cardiovascular disease, the elevated levels of HDL-TG have been related to the increased risk of ischemic heart disease. Furthermore, understanding how tamoxifen influences LTP I activity provides valuable insight into how the administration of tamoxifen modifies plasma lipoprotein-lipid levels.
authors.affiliation: Division of Pharmaceutics and Biopharmaceutics, Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, Canada.
authors.forename: K M
authors.initials: KM
authors.lastname: Wasan
authors.forename: M
authors.initials: M
authors.lastname: Ramaswamy
authors.forename: J
authors.initials: J
authors.lastname: Haley
authors.forename: B P
authors.initials: BP
authors.lastname: Dunn
mesh_terms: D000368:Aged; D018931:Antineoplastic Agents, Hormonal / Q000008:administration & dosage / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000097:blood* / Q000517:prevention & control; D002352:Carrier Proteins / Q000097:blood*; D002784:Cholesterol / Q000097:blood*; D053480:Cholesterol Ester Transfer Proteins; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D015243:Cholesterol, VLDL / Q000097:blood; D005260:Female; D006023:Glycoproteins / Q000097:blood*; D006801:Humans; D008875:Middle Aged; D017698:Postmenopause / Q000097:blood*; D013629:Tamoxifen / Q000008:administration & dosage / Q000627:therapeutic use*; D014280:Triglycerides / Q000097:blood*
chemical_list: D018931:Antineoplastic Agents, Hormonal; C506642:CETP protein, human; D002352:Carrier Proteins; D053480:Cholesterol Ester Transfer Proteins; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D015243:Cholesterol, VLDL; D006023:Glycoproteins; D014280:Triglycerides; D013629:Tamoxifen; D002784:Cholesterol