Skip to main content

Advertisement

SpringerLink
Log in

Tamoxifen: From breast cancer therapy to the design of a postmenopausal prevention maintenance therapy

  • Published:
Osteoporosis International Aims and scope Submit manuscript

Conclusions

There are now exciting opportunities for developing a new prevention maintenance therapy for postmeno-pausal women. These strategies hold the promise of retarding the development of osteoporosis, coronary heart disease, and breast and endometrial cancer. An understanding of the molecular events involved in the target-site-specific effects of estrogen through a novel ERβ system or the selective activation of genes by antiestrogen through novel response elements provides a basis for new drug discovery in the future. However, for the present, the well-documented clinical effects of estrogen coupled with the expanding data base with tamoxifen have laid the foundation for the current clinical trials with raloxifene. Clinical studies with a large population of postmenopausal women will soon establish the efficacy of the drug to treat and prevent osteoporosis, and ancillary studies will confirm its actions in preventing breast cancer and coronary heart disease. Raloxifene is the first of a series of new agents that holds the potential to revolutionize the approach to disease prevention in the majority of postmenopausal women.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Grodstein F, Stampfer M. The epidemiology of coronary heart disease and estrogen replacement in postmenopausal women. Prog Cardiovasc Dis 1995;38:199–210

    Google Scholar 

  2. Lindsay R, Tohme JF. Oestrogen treatment of patients with established postmenopausal osteoporosis. Obstet Gynecol 1990;76:290–5.

    Google Scholar 

  3. Tang M-X, Jacobs D, Stern Y, et al. Effect of oestrogen during menopause on risk and age at onset of Alzheimer's disease. Lancet 1996;348:429–432.

    Google Scholar 

  4. Sherwin BB. Hormones, mood, and cognitive functioning in postmenopausal women. Obstet Gynecol 1996;87:S20–6.

    Google Scholar 

  5. Cohen CJ, Rahaman J. Endometrial cancer: management of high risk and recurrence including the tamoxifen controversy. Cancer 1995;76:2044–52.

    Google Scholar 

  6. Steinberg KK, Thacker SB, Smith SJ, et al. A meta-analysis of the effect of estrogen replacement therapy on the risk of breast cancer. JAMA 1991;265:1985–90.

    Google Scholar 

  7. Early Breast Cancer Trialists' Collaborative Group. Systemic treatment of early breast cancer by hormonal, cytotoxic or immune therapy. Lancet 1992;339:1–15, 71–85.

    Google Scholar 

  8. Love RR, Wiebe DA, Newcomb PA, et al. Effects of tamoxifen oncardivascular risk factors in postmenopausal women. Ann Intern Med 1991;115:860–4.

    Google Scholar 

  9. McDonald CC, Stewart JH, for the Scottish Breast Cancer Committee. Fatal myocardial infarctions in the Scottish adjuvant tamoxifen trial. BMJ 1991;303:435–7.

    Google Scholar 

  10. Love RR, Mazess RB, Barden HS, Epstein S, et al. Effects of tamoxifen on bone mineral density in postmenopausal women with breast cancer. N Engl J Med 1992;326:852–6.

    Google Scholar 

  11. Assikis VJ, Neven P, Jordan VC, Vergote I. A realistic clinical perspective of tamoxifen and endometrial carcinogenesis. Eur J Cancer 1996;32A:1464–6.

    Google Scholar 

  12. Jordan VC. A current view of tamoxifen for the treatment and prevention of breast cancer. Br J Pharmacol 1993;110:507–17.

    Google Scholar 

  13. Powles TJ, Hardy JR, Ashley SE, Farrington GM, et al. A pilot trial to evaluate the acute toxicity and feasibility of tamoxifen for prevention of breast cancer. Br J Cancer 1989;60:126–33.

    Google Scholar 

  14. Powles TJ, Tillyer CP, Jones AL, et al. Prevention of breast cancer with tamoxifen: an update on the Royal Marsden pilot program. Eur J Cancer 1990;26:680–4.

    Google Scholar 

  15. Powles TJ, Jones AL, Ashley SE, et al. The Royal Marsden Hospital pilot tamoxifen chemoprevention trial. Breast Cancer Res Treat 1994;31:73–82.

    Google Scholar 

  16. Powles TJ, Hickish T, Kanis JA, 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;14:78–84.

    Google Scholar 

  17. Jordan VC, Morrow M. An appraisal of strategies to reduce the incidence of breast cancer. Stem Cells 1993;11:252–62.

    Google Scholar 

  18. Lerner LJ, Jordan VC. Development of antiestrogens and their use in breast cancer (Eighth Cain Memorial award lecture). Cancer Res 1990;50:4177–89.

    Google Scholar 

  19. Jordan VC. Alternate antiestrogens and approaches to the prevention of breast cancer. J Cell Biochem Suppl 1995;22:51–7.

    Google Scholar 

  20. Tonetti DA, Jordan VC. Targeted antiestrogens to treat and prevent diseases in women. Mol Med Today 1996;2:218–23.

    Google Scholar 

  21. Tonetti DA, Jordan VC. Design of an ideal hormone replacement therapy for women. Mol Carcinog 1996;17:108–111.

    Google Scholar 

  22. Kuiper GGJM, Enmark E, Pelto-Huikko M, Nilsson S, Gustafsson J-A. Cloning of a novel estrogen receptor expressed in rat prostate and ovary. Proc Natl Acad Sci USA 1996;93:5925–30.

    Google Scholar 

  23. Baniahamad C, Nawaz Z, Banaihmad A, Glesson MAG, Tsai M-J, O'Malley BW. Enhancement of human estrogen receptor activity by SPT6: a potential coactivator. Mol Endocrinol 1995;9:34–43.

    Google Scholar 

  24. Yang NN, Venugopalan M, Hardikar S, Glasebrook A. Identification of an estrogen response element activated by metabolites of 17β-estradiol and raloxifene. Science 1996;273:1222–4.

    Google Scholar 

  25. Gradishar WJ, Jordan VC. The clinical potential of new antiestrogens. J Clin Oncol 1997 (in press).

  26. Ke HZ, Simmons HA, Pirie CM, Crawford DT, Thompson DD. Droloxifene, a new estrogen antagonist/agonist, prevents bone loss in ovariectomized rats. Endocrinology 1995;136:2435–41.

    Google Scholar 

  27. Raushning W, Pritchard KI. Droloxifene, a new antiestrogen: its role in metastatic breast cancer. Breast Cancer Res Treat 1994;31:83–94.

    Google Scholar 

  28. White INH, deMatteis F, Davies A, et al. Genotoxic potential of tamoxifen and analogues in female Fischer 344/n rats, DBA/2 and C57BL/6 mice and in human MCL-5 cells. Carcinogenesis 1992;13:2197–203.

    Google Scholar 

  29. Hasman M, Rattel B, Loser R, Preclinical data for droloxifene. Cancer Lett 1994;84:101–16.

    Google Scholar 

  30. Jordan VC, Phelps E, Lindgren JU. Effect of antiestrogens on bone in castrated and intact female rats. Breast Cancer Res Treat 1987;10:31–5.

    Google Scholar 

  31. Gottardis MM, Jordan VC. The antitumor action of keoxifene and tamoxifen in the JV-nitrosomethylurea-induced rat mammary carcinoma model. Cancer Res 1987;47:4020–4.

    Google Scholar 

  32. Black LJ, Sato M, Rowley ER, et al. (1994) Raloxifene (LY139481 HC1) prevents bone loss and reduces serum cholesterol without causing uterine hypotrophy in ovariectomized rats. J Clin Invest 93:63–9

    Google Scholar 

  33. Evans GL, Bryant HU, Magee D, Sato M, Turner RT. The effects of raloxifene on tibia histomorphometry in ovariectomized rats. Endocrinology 1994;134:2283–8.

    Google Scholar 

  34. Sato M, Kim J, Short LL, Szemenda CW, Bryant HU. Longitudinal and cross-sectional analysis of raloxifene effects on tibiae from ovariectomized rats. J Pharmacol Exp Ther 1995;272:1251–9.

    Google Scholar 

  35. Black LJ, Jones CD, Falcone JF. Antagonism of estrogen action with a new benzothiophene-derived antiestrogen. Life Sci 1983;32:1031–6.

    Google Scholar 

  36. Biegon A, Brewster M, Degani H, Pop E, Somjen D, Kaye AM. A permanently charged tamoxifen derivative displays anticancer activity and improved tissue selectivity in rodents. Cancer Res 1996;56:4328–31.

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Robert H. Lurie Cancer Center, Northwestern University Medical School, Olson Pavilion 8256, 303 E. Chicago Avenue, 60611, Chicago, IL, USA

    V. C. Jordan, J. I. MacGregor & D. A. Tonetti

Authors
  1. V. C. Jordan
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. J. I. MacGregor
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. D. A. Tonetti
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Jordan, V.C., MacGregor, J.I. & Tonetti, D.A. Tamoxifen: From breast cancer therapy to the design of a postmenopausal prevention maintenance therapy. Osteoporosis Int 7 (Suppl 1), 52–57 (1997). https://doi.org/10.1007/BF01674814

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF01674814

Keywords

Search

Navigation