Skip to main content
NCBI home page
British Journal of Cancer logoLink to British Journal of Cancer
. 1998 Sep;78(5):572–578. doi: 10.1038/bjc.1998.542

Effect of tamoxifen and transdermal hormone replacement therapy on cardiovascular risk factors in a prevention trial. Italian Chemoprevention Group.

A Decensi 1, C Robertson 1, N Rotmensz 1, G Severi 1, P Maisonneuve 1, V Sacchini 1, P Boyle 1, A Costa 1, U Veronesi 1
PMCID: PMC2063049  PMID: 9744493

Abstract

The combination of tamoxifen and transdermal hormone replacement therapy (HRT) may potentially reduce risks and side-effects of either agent, but an adverse interaction could attenuate their beneficial effects. We assessed the effects of their combination on cardiovascular risk factors within a prevention trial of tamoxifen. Baseline and 12-month measurements of total, low-density lipoprotein (LDL)- and high-density lipoprotein (HDL)-cholesterol, platelets and white blood cells were obtained in the following four groups: tamoxifen (n = 1117), placebo (n = 1112), tamoxifen and HRT (n = 68), placebo and HRT (n = 87). The analysis was further extended to women who were on HRT at randomization but discontinued it during the 12-month intervention period (n = 33 on tamoxifen and n = 35 on placebo) and to women who were not on HRT but started it during intervention (n = 36 in both arms of the study). Compared with small changes in the placebo group, tamoxifen was associated with changes in total, LDL- and HDL-cholesterol of approximately -9%, -19% and +0.2% in continuous HRT users compared with -9%, -14% and -0.8% in never HRT users. Similarly, there was no interaction on platelet count. In contrast, the decrease in total and LDL-cholesterol levels induced by tamoxifen was blunted by two-thirds in women who started HRT while on tamoxifen (P = 0.051 for the interaction term). We conclude that the beneficial effects of tamoxifen on cardiovascular risk factors are unchanged in current HRT users, whereas they may be attenuated in women who start transdermal HRT while on tamoxifen. Whereas a trial of tamoxifen in women already on transdermal HRT is warranted, prescription of HRT during tamoxifen may attenuate its activity.

Full text

PDF
572

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Assikis V. J., Neven P., Jordan V. C., Vergote I. A realistic clinical perspective of tamoxifen and endometrial carcinogenesis. Eur J Cancer. 1996 Aug;32A(9):1464–1476. doi: 10.1016/0959-8049(96)00184-0. [DOI] [PubMed] [Google Scholar]
  2. Belchetz P. E. Hormonal treatment of postmenopausal women. N Engl J Med. 1994 Apr 14;330(15):1062–1071. doi: 10.1056/NEJM199404143301508. [DOI] [PubMed] [Google Scholar]
  3. Chang J., Powles T. J., Ashley S. E., Gregory R. K., Tidy V. A., Treleaven J. G., Singh R. The effect of tamoxifen and hormone replacement therapy on serum cholesterol, bone mineral density and coagulation factors in healthy postmenopausal women participating in a randomised, controlled tamoxifen prevention study. Ann Oncol. 1996 Sep;7(7):671–675. doi: 10.1093/oxfordjournals.annonc.a010715. [DOI] [PubMed] [Google Scholar]
  4. Chetkowski R. J., Meldrum D. R., Steingold K. A., Randle D., Lu J. K., Eggena P., Hershman J. M., Alkjaersig N. K., Fletcher A. P., Judd H. L. Biologic effects of transdermal estradiol. N Engl J Med. 1986 Jun 19;314(25):1615–1620. doi: 10.1056/NEJM198606193142505. [DOI] [PubMed] [Google Scholar]
  5. Colvin P. L., Jr, Auerbach B. J., Koritnik D. R., Hazzard W. R., Applebaum-Bowden D. Differential effects of oral estrone versus 17 beta-estradiol on lipoproteins in postmenopausal women. J Clin Endocrinol Metab. 1990 Jun;70(6):1568–1573. doi: 10.1210/jcem-70-6-1568. [DOI] [PubMed] [Google Scholar]
  6. Costantino J. P., Kuller L. H., Ives D. G., Fisher B., Dignam J. Coronary heart disease mortality and adjuvant tamoxifen therapy. J Natl Cancer Inst. 1997 Jun 4;89(11):776–782. doi: 10.1093/jnci/89.11.776. [DOI] [PubMed] [Google Scholar]
  7. Fisher B., Costantino J. P., Redmond C. K., Fisher E. R., Wickerham D. L., Cronin W. M. 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. 1994 Apr 6;86(7):527–537. doi: 10.1093/jnci/86.7.527. [DOI] [PubMed] [Google Scholar]
  8. Friedewald W. T., Levy R. I., Fredrickson D. S. Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clin Chem. 1972 Jun;18(6):499–502. [PubMed] [Google Scholar]
  9. Gillum R. F., Ingram D. D., Makuc D. M. White blood cell count, coronary heart disease, and death: the NHANES I Epidemiologic Follow-up Study. Am Heart J. 1993 Mar;125(3):855–863. doi: 10.1016/0002-8703(93)90181-8. [DOI] [PubMed] [Google Scholar]
  10. Grodstein F., Stampfer M. J., Colditz G. A., Willett W. C., Manson J. E., Joffe M., Rosner B., Fuchs C., Hankinson S. E., Hunter D. J. Postmenopausal hormone therapy and mortality. N Engl J Med. 1997 Jun 19;336(25):1769–1775. doi: 10.1056/NEJM199706193362501. [DOI] [PubMed] [Google Scholar]
  11. Grodstein F., Stampfer M. J., Manson J. E., Colditz G. A., Willett W. C., Rosner B., Speizer F. E., Hennekens C. H. Postmenopausal estrogen and progestin use and the risk of cardiovascular disease. N Engl J Med. 1996 Aug 15;335(7):453–461. doi: 10.1056/NEJM199608153350701. [DOI] [PubMed] [Google Scholar]
  12. Handin R. I. Platelets and coronary artery disease. N Engl J Med. 1996 Apr 25;334(17):1126–1127. doi: 10.1056/NEJM199604253341710. [DOI] [PubMed] [Google Scholar]
  13. Holme I. An analysis of randomized trials evaluating the effect of cholesterol reduction on total mortality and coronary heart disease incidence. Circulation. 1990 Dec;82(6):1916–1924. doi: 10.1161/01.cir.82.6.1916. [DOI] [PubMed] [Google Scholar]
  14. Jaiyesimi I. A., Buzdar A. U., Decker D. A., Hortobagyi G. N. Use of tamoxifen for breast cancer: twenty-eight years later. J Clin Oncol. 1995 Feb;13(2):513–529. doi: 10.1200/JCO.1995.13.2.513. [DOI] [PubMed] [Google Scholar]
  15. Jordan V. C., Fritz N. F., Langan-Fahey S., Thompson M., Tormey D. C. Alteration of endocrine parameters in premenopausal women with breast cancer during long-term adjuvant therapy with tamoxifen as the single agent. J Natl Cancer Inst. 1991 Oct 16;83(20):1488–1491. doi: 10.1093/jnci/83.20.1488. [DOI] [PubMed] [Google Scholar]
  16. Katzenellenbogen B. S. Estrogen receptors: bioactivities and interactions with cell signaling pathways. Biol Reprod. 1996 Feb;54(2):287–293. doi: 10.1095/biolreprod54.2.287. [DOI] [PubMed] [Google Scholar]
  17. Kinosian B., Glick H., Garland G. Cholesterol and coronary heart disease: predicting risks by levels and ratios. Ann Intern Med. 1994 Nov 1;121(9):641–647. doi: 10.7326/0003-4819-121-9-199411010-00002. [DOI] [PubMed] [Google Scholar]
  18. Love R. R., Cameron L., Connell B. L., Leventhal H. Symptoms associated with tamoxifen treatment in postmenopausal women. Arch Intern Med. 1991 Sep;151(9):1842–1847. [PubMed] [Google Scholar]
  19. Love R. R., Newcomb P. A., Wiebe D. A., Surawicz T. S., Jordan V. C., Carbone P. P., DeMets D. L. Effects of tamoxifen therapy on lipid and lipoprotein levels in postmenopausal patients with node-negative breast cancer. J Natl Cancer Inst. 1990 Aug 15;82(16):1327–1332. doi: 10.1093/jnci/82.16.1327. [DOI] [PubMed] [Google Scholar]
  20. Lukac J., Kusić Z., Kordić D., Koncar M., Bolanca A. Natural killer cell activity, phagocytosis, and number of peripheral blood cells in breast cancer patients treated with tamoxifen. Breast Cancer Res Treat. 1994;29(3):279–285. doi: 10.1007/BF00666482. [DOI] [PubMed] [Google Scholar]
  21. McDonald C. C., Alexander F. E., Whyte B. W., Forrest A. P., Stewart H. J. Cardiac and vascular morbidity in women receiving adjuvant tamoxifen for breast cancer in a randomised trial. The Scottish Cancer Trials Breast Group. BMJ. 1995 Oct 14;311(7011):977–980. doi: 10.1136/bmj.311.7011.977. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Nachtigall L. E. Emerging delivery systems for estrogen replacement: aspects of transdermal and oral delivery. Am J Obstet Gynecol. 1995 Sep;173(3 Pt 2):993–997. doi: 10.1016/0002-9378(95)90249-x. [DOI] [PubMed] [Google Scholar]
  23. Newcomb P. A., Storer B. E. Postmenopausal hormone use and risk of large-bowel cancer. J Natl Cancer Inst. 1995 Jul 19;87(14):1067–1071. doi: 10.1093/jnci/87.14.1067. [DOI] [PubMed] [Google Scholar]
  24. Pennisi E. Drug's link to genes reveals estrogen's many sides. Science. 1996 Aug 30;273(5279):1171–1171. doi: 10.1126/science.273.5279.1171. [DOI] [PubMed] [Google Scholar]
  25. Powles T. J., Hickish T., Casey S., O'Brien M. Hormone replacement after breast cancer. Lancet. 1993 Jul 3;342(8862):60–61. doi: 10.1016/0140-6736(93)91931-b. [DOI] [PubMed] [Google Scholar]
  26. Powles T. J., Hickish T., Kanis J. A., Tidy A., Ashley S. Effect of tamoxifen on bone mineral density measured by dual-energy x-ray absorptiometry in healthy premenopausal and postmenopausal women. J Clin Oncol. 1996 Jan;14(1):78–84. doi: 10.1200/JCO.1996.14.1.78. [DOI] [PubMed] [Google Scholar]
  27. Powles T. J., Jones A. L., Ashley S. E., O'Brien M. E., Tidy V. A., Treleavan J., Cosgrove D., Nash A. G., Sacks N., Baum M. The Royal Marsden Hospital pilot tamoxifen chemoprevention trial. Breast Cancer Res Treat. 1994;31(1):73–82. doi: 10.1007/BF00689678. [DOI] [PubMed] [Google Scholar]
  28. Riggs B. L., Melton L. J., 3rd The prevention and treatment of osteoporosis. N Engl J Med. 1992 Aug 27;327(9):620–627. doi: 10.1056/NEJM199208273270908. [DOI] [PubMed] [Google Scholar]
  29. Rosenberg L., Hennekens C. H., Rosner B., Belanger C., Rothman K. J., Speizer F. E. Early menopause and the risk of myocardial infarction. Am J Obstet Gynecol. 1981 Jan;139(1):47–51. doi: 10.1016/0002-9378(81)90410-5. [DOI] [PubMed] [Google Scholar]
  30. Rutqvist L. E., Johansson H., Signomklao T., Johansson U., Fornander T., Wilking N. Adjuvant tamoxifen therapy for early stage breast cancer and second primary malignancies. Stockholm Breast Cancer Study Group. J Natl Cancer Inst. 1995 May 3;87(9):645–651. doi: 10.1093/jnci/87.9.645. [DOI] [PubMed] [Google Scholar]
  31. Rutqvist L. E., Mattsson A. Cardiac and thromboembolic morbidity among postmenopausal women with early-stage breast cancer in a randomized trial of adjuvant tamoxifen. The Stockholm Breast Cancer Study Group. J Natl Cancer Inst. 1993 Sep 1;85(17):1398–1406. doi: 10.1093/jnci/85.17.1398. [DOI] [PubMed] [Google Scholar]
  32. Slowinska-Srzednicka J., Zgliczynski S., Jeske W., Stopinska-Gluszak U., Srzednicki M., Brzezinska A., Zgliczynski W., Sadowski Z. Transdermal 17 beta-estradiol combined with oral progestogen increases plasma levels of insulin-like growth factor-I in postmenopausal women. J Endocrinol Invest. 1992 Jul-Aug;15(7):533–538. doi: 10.1007/BF03348801. [DOI] [PubMed] [Google Scholar]
  33. Smigel K. Breast Cancer Prevention Trial shows major benefit, some risk. J Natl Cancer Inst. 1998 May 6;90(9):647–648. doi: 10.1093/jnci/90.9.647. [DOI] [PubMed] [Google Scholar]
  34. Thaulow E., Erikssen J., Sandvik L., Stormorken H., Cohn P. F. Blood platelet count and function are related to total and cardiovascular death in apparently healthy men. Circulation. 1991 Aug;84(2):613–617. doi: 10.1161/01.cir.84.2.613. [DOI] [PubMed] [Google Scholar]
  35. Van Erpecum K. J., Van Berge Henegouwen G. P., Verschoor L., Stoelwinder B., Willekens F. L. Different hepatobiliary effects of oral and transdermal estradiol in postmenopausal women. Gastroenterology. 1991 Feb;100(2):482–488. doi: 10.1016/0016-5085(91)90220-f. [DOI] [PubMed] [Google Scholar]
  36. Walsh B. W., Li H., Sacks F. M. Effects of postmenopausal hormone replacement with oral and transdermal estrogen on high density lipoprotein metabolism. J Lipid Res. 1994 Nov;35(11):2083–2093. [PubMed] [Google Scholar]
  37. Yang N. N., Venugopalan M., Hardikar S., Glasebrook A. Identification of an estrogen response element activated by metabolites of 17beta-estradiol and raloxifene. Science. 1996 Aug 30;273(5279):1222–1225. doi: 10.1126/science.273.5279.1222. [DOI] [PubMed] [Google Scholar]

Articles from British Journal of Cancer are provided here courtesy of Cancer Research UK

RESOURCES