title: The influence of letrozole on serum lipid concentrations in postmenopausal women with primary breast cancer who have completed 5 years of adjuvant tamoxifen (NCIC CTG MA.17L).
abstract: BACKGROUND
  The purpose of this study was to evaluate changes in serum lipid parameters {cholesterol, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, triglycerides and lipoprotein(a) [Lp(a)]}, in postmenopausal women receiving letrozole or placebo after adjuvant tamoxifen for early stage breast cancer (NCIC CTG MA.17L).
  
  
  METHODS
  MA.17L is a substudy of MA.17, a randomized, double-blind, placebo-controlled trial of letrozole 2.5 mg taken daily for 5 years in postmenopausal women with primary breast cancer completing approximately 5 years of prior adjuvant tamoxifen. Patients consenting to participate in this companion study had blood drawn and lipid parameters (total cholesterol, HDL cholesterol, LDL cholesterol, Lp(a), triglycerides) evaluated at baseline, 6 months, 12 months and yearly thereafter until completion of protocol therapy. It was required that women be non-hyperlipidemic and not taking lipid-lowering drugs at time of entry on this trial.
  
  
  RESULTS
  Three hundred and forty seven women were enrolled in the study. The letrozole and the placebo groups demonstrated marginally significant differences in the percentage change from baseline in HDL cholesterol at 6 months (P=0.049), in LDL cholesterol at 12 months (P=0.033) and triglycerides at 24 months (P=0.036). All comparisons of lipid parameters at other time points were not significantly different between the two treatment groups. No statistically significant differences in the number of patients exceeding the thresholds defined for the lipid parameters were found between the two treatment groups.
  
  
  CONCLUSIONS
  The MA.17 trial demonstrated a significant improvement in disease-free survival with the use of letrozole as extended adjuvant therapy post tamoxifen. Results from this study suggests that letrozole does not significantly alter serum cholesterol, HDL cholesterol, LDL cholesterol, triglycerides or Lp(a) in non-hyperlidiemic postmenopausal women with primary breast cancer treated up to 36 months following at least 5 years of adjuvant tamoxifen therapy. These findings further support the tolerability of extended adjuvant letrozole in postmenopausal women following standard tamoxifen therapy.
authors.affiliation: Division of Pharmaceutics and Biopharmaceutics, Faculty of Pharmaceutical Sciences, The University of British Columbia, Vancouver, BC, Canada. kwasan@interchange.ubc.ca
authors.forename: K M
authors.initials: KM
authors.lastname: Wasan
authors.forename: P E
authors.initials: PE
authors.lastname: Goss
authors.forename: P H
authors.initials: PH
authors.lastname: Pritchard
authors.forename: L
authors.initials: L
authors.lastname: Shepherd
authors.forename: M J
authors.initials: MJ
authors.lastname: Palmer
authors.forename: S
authors.initials: S
authors.lastname: Liu
authors.forename: D
authors.initials: D
authors.lastname: Tu
authors.forename: J N
authors.initials: JN
authors.lastname: Ingle
authors.forename: M
authors.initials: M
authors.lastname: Heath
authors.forename: D
authors.initials: D
authors.lastname: Deangelis
authors.forename: E A
authors.initials: EA
authors.lastname: Perez
mesh_terms: D000368:Aged; D047072:Aromatase Inhibitors / Q000493:pharmacokinetics / Q000627:therapeutic use; D001682:Biological Availability; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology / Q000601:surgery; D017024:Chemotherapy, Adjuvant; D008076:Cholesterol, HDL / Q000097:blood*; D008078:Cholesterol, LDL / Q000097:blood*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D000077289:Letrozole; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D009570:Nitriles / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D017698:Postmenopause; D011336:Probability; D012016:Reference Values; D018570:Risk Assessment; D018709:Statistics, Nonparametric; D016019:Survival Analysis; D013629:Tamoxifen / Q000627:therapeutic use*; D016896:Treatment Outcome; D014230:Triazoles / Q000493:pharmacokinetics* / Q000627:therapeutic use*
chemical_list: D047072:Aromatase Inhibitors; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D009570:Nitriles; D014230:Triazoles; D013629:Tamoxifen; D000077289:Letrozole