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Breast Cancer Research and Treatment

, Volume 79, Issue 1, pp 11–16 | Cite as

Sequential Changes in Serum Triglyceride Levels During Adjuvant Tamoxifen Therapy in Breast Cancer Patients and the Effect of Dose Reduction

  • Chien-Liang Liu
  • Tsen-Long Yang
Article

Abstract

Tamoxifen (TAM) and estrogen increase serum triglyceride (TG) levels, sometimes inducing severe hypertriglyceridemia and possibly contributing to death. Decreasing the dose of estrogen in estrogen replacement therapy may minimize its adverse effects, including the hypertriglyceridemia. The serum TG, total cholesterol, low-density-lipoprotein (LDL) cholesterol and high-density-lipoprotein (HDL) cholesterol were measured periodically in 116 breast cancer patients on adjuvant TAM therapy at a dose of 10 mg twice daily. The serum TG level was significantly increased 15 months after treatment, but the magnitude of increase was clinically insignificant in most patients (n = 102). If TG levels rose above 400 mg/dl, the dose of TAM was reduced to 10 mg once daily (n = 14). The TG was lowered to a safer level after the dose reduction of TAM in 10 of 14 patients. The other four patients had early onset hypertriglyceridemia after beginning TAM (within 6 months), and their TG levels did not decrease satisfactorily after dose reduction. Hence, they required antilipemic medication with or without discontinuing TAM. This study suggests that reducing TAM from 10 mg twice daily to 10 mg once daily decreases the marked hypertriglyceridemia that occurs in some patients during TAM treatment.

breast cancer dose reduction hypertriglyceridemia serum triglyceride level tamoxifen 

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References

  1. 1.
    Coezy E, Borgna JL, Rochefort H: Tamoxifen and metabolites in MCF7 cells: correlation between binding to estrogen receptor and inhibition of cell growth. Cancer Res 42: 317–323, 1982Google Scholar
  2. 2.
    Sutherland RL, Watts CKW, Hall RE, Ruenitz PC: Mechanisms of growth inhibition by nonsteroidal antiestrogens in human breast cancer cells. J Steroid Biochem 27: 891–897, 1987Google Scholar
  3. 3.
    Robinson E, Kimmick GG, Muss HB: Tamoxifen in postmenopausal women: a safety perspective. Drugs Aging 8: 329–337, 1996Google Scholar
  4. 4.
    Early Breast Cancer Trialists' Collaborative Group: Tamoxifen for early breast cancer: an overview of the randomized trials. Lancet 351: 1451–1467, 1998Google Scholar
  5. 5.
    Decensi A, Bonanni B, Guerrieri-Gonzaga A, Gandini S, Robertson C, Johansson H, Travaglini R, Sandri MT, Tessadrelli A, Farante G, Salinaro F, Bettega D, Barreca A, Boyle P, Costa A, Veronesi U: Biologic activity of tamoxifen at low doses in healthy women. J Natl Cancer Inst 90: 1461–1467, 1998Google Scholar
  6. 6.
    Pavlidis NA, Petris C, Briassoulis E, Klouvas G, Psilas C, Rempapis J, Petroutsos G: Clear evidence that long-term, low-dose tamoxifen treatment can induce ocular toxicity: a prospective study of 63 patients. Cancer 69: 2961–2964, 1992Google Scholar
  7. 7.
    Wogan GN: Review of toxicology of tamoxifen. Semin Oncol 24(Suppl 1): S1-87–S1-97, 1997Google Scholar
  8. 8.
    Bruning PF, Bonfrer JMG, Hart AAM, de Jong-Bakker M, Linders D, van Loon J, Nooyen WJ: Tamoxifen, serum lipoproteins and cardiovascular risk. Br J Cancer 58: 497–499, 1988Google Scholar
  9. 9.
    Bagdade JD, Wolter J, Subbaiah PV, Ryan W: Effects of tamoxifen treatment on plasma lipids and lipoprotein lipid composition. J Clin Endocrinol Metab 70: 1132–1135, 1990Google Scholar
  10. 10.
    Love RR, Wiebe DA, Newcomb PA, Cameron L, Leventhal H, Jordan VC, Feyzi J, DeMets DL: Effects of tamoxifen on cardiovascular risk factors in postmenopausal women. Ann Int Med 115: 860–864, 1991Google Scholar
  11. 11.
    Hozumi Y, Kawano M, Saito T, Miyata M: Effect of tamoxifen on serum lipid metabolism. J Clin Endocrinol Metab 83: 1633–1635, 1998Google Scholar
  12. 12.
    Brun LD, Gagne C, Rousseau C, Moorjani S, Lupien PJ: Severe lipemia induced by tamoxifen. Cancer 57: 2123–2126, 1986Google Scholar
  13. 13.
    Noguchi M, Taniya T, Tajiri K, Miwa K, Miyazaki I, Koshino H, Mabuchi H, Nonomura A: Fatal hyperlipaemia in a case of metastatic breast cancer treated by tamoxifen. Br J Surg 74: 586–587, 1987Google Scholar
  14. 14.
    Elisaf MS, Nakou K, Liamis G, Pavlidis NA: Tamoxifeninduced severe hypertriglyceridemia and pancreatitis. Ann Oncol 11: 1067–1069, 2000Google Scholar
  15. 15.
    Fisher B, Costantino JP, Redmond CK, Fisher ER, Wickerham DL, Cronin WM, Other NSABP Contributors: Endometrial cancer in tamoxifen-treated breast cancer patients: findings from the National Surgical Adjuvant Breast and Bowel Project (NSABP) B-14. J Natl Cancer Inst 86: 527–537, 1994Google Scholar
  16. 16.
    Rutqvist LE, Johansson H, Signomklao T, Johansson U, Fornander T, Wilking N: Adjuvant tamoxifen therapy for early stage breast cancer and second primary malignancies. J Natl Cancer Inst 87: 645–651, 1995Google Scholar
  17. 17.
    Walsh BW, Schiff I, Rosner B, Greenberg L, Ravnikar V, Sacks FM: Effects of postmenopausal estrogen replacement on the concentrations and metabolism of plasma lipoproteins. N Engl J Med 325: 1196–1204, 1991Google Scholar
  18. 18.
    Bertelli G, Pronzato P, Amoroso D, Cusimano MP, Conte PF, Montagna G, Bertolini S, Rosso R: Adjuvant tamoxifen in primary breast cancer: influence on plasma lipids and antithrombin III levels. Breast Cancer Res Treat 12: 307–310, 1988Google Scholar
  19. 19.
    Gylling H, Pyrhonen S, Mantyla E, Maenpaa H, Kangas L, Miettinen TA: Tamoxifen and toremifene lower serum cholesterol by inhibition of Δ8-cholesterol conversion to lathosterol in women with breast cancer. J Clin Oncol 13: 2900–2905, 1995Google Scholar
  20. 20.
    Rader DJ, Rosas S: Management of selected lipid abnormalities: hypertriglyceridemia, low HDL cholesterol, lipoprotein(a) in thyroid and renal diseases and post-transplantation. Med Clin North Am 84: 43–61, 2000Google Scholar
  21. 21.
    Council on Scientific Affairs: Management of disorders of cholesterol, triglyceride, and lipoprotein metabolism: report 6 of the Council on Scientific Affairs. Arch Fam Med 4: 869–878, 1995Google Scholar
  22. 22.
    Decensi A, Gandini S, Guerrieri-Gonzaga A, Johansson H, Manetti L, Bonanni B, Sandri MT, Barreca A, Costa A, Robertson C, Lien EA: Effect of blood tamoxifen concentrations on surrogate biomarkers in a trial of dose reduction in healthy women. J Clin Oncol 17: 2633–2638, 1999Google Scholar
  23. 23.
    Bernardes JRM, Nonogaki S, Seixas MT, de Lima GR, Baracat EC, Gebrim LH: Effect of a half dose of tamoxifen on proliferative activity in normal breast tissue. Int J Gynecol Obstet 67: 33–38, 1999Google Scholar

Copyright information

© Kluwer Academic Publishers 2003

Authors and Affiliations

  • Chien-Liang Liu
    • 1
  • Tsen-Long Yang
    • 1
  1. 1.Department of General SurgeryMackay Memorial HospitalTaipeiTaiwan

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