TAMOXIFEN AND TOREMIFENE LOWER SERUM-CHOLESTEROL BY INHIBITION OF DELTA(8)-CHOLESTENOL CONVERSION TO LATHOSTEROL IN WOMEN WITH BREAST-CANCER

Purpose: Long-term effects of tamoxifen and toremifene, a new antiestr ogen that closely resembles tamoxifen, were investigated on serum lipi ds and cholesterol metabolism. Patients and Methods: The study group c onsisted of 24 postmenopausal Finnish women with advanced breast cance r from an international multicenter study of 415 patients. Cholesterol metabolism was evaluated by measuring the cholesterol precursor (Delt a(8)-cholestenol, desmosterol, and lathosterol, reflecting cholesterol synthesis) and plant sterol (markers of cholesterol absorption) and c holestanol levels by gas-liquid chromatography. Results: Tamoxifen and toremifene lowered significantly serum low-density lipoprotein (LDL) cholesterol levels after 12 months of treatment by 16% and 15%, with n o change in high-density lipoprotein (HDL) cholesterol or serum trigly ceride levels, Serum Delta(8)-cholestenol was increased 40- and 55-fol d during toremifene and tamoxifen treatment, respectively, while the i ncrease of desmosterol less than doubled and was lacking for lathoster ol by toremifene. Plant sterols and cholestanol were only inconsistent ly increased in serum. Conclusion: Tamoxifen and toremifene inhibit th e conversion of Delta(8)-cholestenol to lathosterol so that serum tota l and LDL cholesterol levels ore lowered by downregulation of choleste rol synthesis. Thus, inhibition of the Delta(8)-isomerase may be the m ajor hypolipidemic effect of these agents, Reduced risk of coronary ar tery disease will probably occur also during long-term toremifene trea tment, because the drug reduces cholesterol and its synthesis, similar ly to tamoxifen. (C) 1995 by American Society of Clinical Oncology.