title: Lipid concentrations in postmenopausal women on letrozole after 5 years of tamoxifen: an NCIC CTG MA.17 sub-study.
abstract: To evaluate changes in serum lipid parameters (cholesterol, HDL cholesterol, LDL cholesterol, triglycerides, and lipoprotein(a) [Lp(a)]), in postmenopausal women receiving letrozole after tamoxifen therapy. MA.17L is a sub-study of MA.17, a double-blind, placebo-controlled trial of extended adjuvant letrozole. Eligible postmenopausal women were non-hyperlipidemic and not on lipid-lowering drugs. This analysis considers the 183 patients on the letrozole arm. Lipid parameters evaluated at baseline, 6 months, 12 months, and yearly thereafter until completion of 5 years of letrozole. The median duration of letrozole treatment was 5.0 years with a range from 0.03 to 6.05 years. After 5 year tamoxifen, patients on letrozole experienced significant increases from baseline in total cholesterol, LDL cholesterol, and Lp(a) at all study time points but no statistically significant changes in triglycerides. Specifically, a statistically significant increase was found at 60 months in total cholesterol [mean percentage change from baseline (PC) 5.27; p = 0.003], HDL cholesterol (mean PC 6.75; p = 0.003), LDL cholesterol (mean PC 10.02; p = 0.001), Lp(a) (mean PC 105.95; p < 0.0001). 103 (56 %) women in the study had clinically significantly elevated levels of Lp(a) (106 % above baseline) after 5 years of therapy. The results were similar after excluding the 21 % of patients who had ever received anti-lipid treatment. Significant increases in total cholesterol, HDL cholesterol, LDL cholesterol, and, most notably, Lp(a) in postmenopausal women were observed following 5 years of adjuvant letrozole treatment and after 5 years of tamoxifen therapy and such patients should have monitoring of their lipid levels in clinical practice.
authors.affiliation: Faculty of Pharmaceutical Sciences, The University of British Columbia, Vancouver, BC, V6T 1Z3, Canada. Kishor.Wasan@ubc.ca
authors.forename: Kishor M
authors.initials: KM
authors.lastname: Wasan
authors.forename: Paul E
authors.initials: PE
authors.lastname: Goss
authors.forename: P Haydn
authors.initials: PH
authors.lastname: Pritchard
authors.forename: Lois
authors.initials: L
authors.lastname: Shepherd
authors.forename: Dongsheng
authors.initials: D
authors.lastname: Tu
authors.forename: James N
authors.initials: JN
authors.lastname: Ingle
mesh_terms: D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D047072:Aromatase Inhibitors / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000097:blood / Q000188:drug therapy*; D017024:Chemotherapy, Adjuvant; D002784:Cholesterol / Q000097:blood; D008076:Cholesterol, HDL / Q000097:blood; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D000077289:Letrozole; D008055:Lipids / Q000097:blood*; D017270:Lipoprotein(a) / Q000097:blood; D008875:Middle Aged; D009570:Nitriles / Q000008:administration & dosage / Q000627:therapeutic use*; D017698:Postmenopause; D013629:Tamoxifen / Q000627:therapeutic use*; D013997:Time Factors; D014230:Triazoles / Q000008:administration & dosage / Q000627:therapeutic use*
chemical_list: D000970:Antineoplastic Agents; D047072:Aromatase Inhibitors; D008076:Cholesterol, HDL; D008055:Lipids; D017270:Lipoprotein(a); D009570:Nitriles; D014230:Triazoles; D013629:Tamoxifen; D000077289:Letrozole; D002784:Cholesterol