Skip to main content
SpringerLink
Log in
Book cover

Hormone Therapy in Breast and Prostate Cancer pp 195–212Cite as

Clinical Utility of New Antiestrogens

  • Chapter

  • 332 Accesses

Part of the book series: Cancer Drug Discovery and Development ((CDD&D))

Abstract

Tamoxifen (Fig. 1) is the endocrine treatment of choice for all stages of hormone-responsive breast cancer. Additionally tamoxifen has been shown to reduce the incidence of cancer of the opposite breast (1) and has recently been demonstrated to prevent breast cancer (2). Although most women with hormone-responsive advanced breast cancer respond to tamoxifen, their disease eventually becomes refractory to tamoxifen. These patients are known to respond to second-line hormonal therapies. In this chapter, we will focus on new antiestrogens that are currently available or are being developed for use following tamoxifen failure. We have divided these new agents into three groups according to their target-site specificity and molecular properties (3); tamoxifen-like agents, raloxifene-like agents, and pure antiestrogens.

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

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   89.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   119.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD   169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Early Breast Cancer Trialists’ Collaborative Group. Tamoxifen for early breast cancer: an overview of the randomized trials. Lancet 1998; 351:1451–1467.

    Google Scholar 

  2. Fisher B, Costantino JP, Wickerham DL, Redmond CK, Kavanah M, Cronin WM, et al. Tamoxifen for prevention of breast cancer: report of the National Surgical Adjuvant breast and Bowel Project P-1 Study. J Natl Cancer Inst 1998; 90:1371–1388.

    Article  PubMed  CAS  Google Scholar 

  3. Schafer JI, Liu H, Tonetti DA, Jordan VC. The interaction of raloxifene and the active metabolite of the antiestrogen EM-800 (SC 5705) with the human estrogen receptor (ER). Cancer Res 1999; 59:4308–4313.

    PubMed  CAS  Google Scholar 

  4. Kangas L, Niemenen A.-L, Blanco G, Gronroos M, Kallio S, Karjalainen A, Perilla M, Soderwall M, Tiovola R. A new triphenylethylene compound Fc-1157a II antitumor effects. Cancer Chemo Pharm 1986; 17:109–113.

    Article  CAS  Google Scholar 

  5. Warri AM, Huovinon RL, Laine AM, Mairtikainen PM, Harkonen PL. Apoptosis in toremifene growth inhibition of human breast cancer cells in vivo and in vitro. J Natl Cancer Inst 1993; 85:1412–1418.

    Article  PubMed  CAS  Google Scholar 

  6. Grenman RL, Laine KM, Klemi PJ, Grenman S, Hayashida DJ, Joensuu H. Effect of the antiestrogen toremifene on growth of human mammary carcinoma cell line MCF-7. J Cancer Res Clin Oncol 1991; 117:223–2268.

    Article  PubMed  CAS  Google Scholar 

  7. Robinson SP, Goldstein D, Witt PL, Borden EC, Jordan VC. Inhibition of hormone dependent and independent breast cancer growth in vivo and in vitro with the antiestrogen toremifene and recombinant human interferon α2. Breast Cancer Res Treat 1990; 15:95–101.

    Article  PubMed  CAS  Google Scholar 

  8. DiSalle E, Zaccheo T, Ornati G. Anioestrogenic and antitumor properties of the new tripphenylethylene derivative toremifene in the rat. J Steroid Biochem 1990; 36:203–206.

    Article  CAS  Google Scholar 

  9. Huovinen R, Warri A, Collan Y. Mitotic activity, apoptosis and TRPM-2 messenger RNA expression in DMBA-induced rat mammary carcinoma treated with the antiestrogen toremifene. Intl J Cancer 1993; 55:685–691.

    Article  CAS  Google Scholar 

  10. Huovinen R, Kellokumpu-Lehtinen PL, Collan Y. Evaluating the response to antiestrogen toremifene treatment in DMBA-induced rat mammary carcinoma Intl J Exp Pathol 1994; 75:257–263.

    CAS  Google Scholar 

  11. Huovinen RL, Alanen KA, Collan Y. Cell proliferation in dimethylbenz(A) anthraceneinduced rat mammary carcinoma treated with antiestrogen toremifene. Acta Oncol 1995; 34:479–485.

    Article  PubMed  CAS  Google Scholar 

  12. Robinson SP, Mauel DA, Jordan VC. Antitumor actions of toremifene in the 7,12 dimethylbenzanthracene (DMBA)-induced rat mammary tumor model. Eur J Cancer 1988; 24:1817–1821.

    Article  CAS  Google Scholar 

  13. Robinson SP, Jordan VC. Antiestrogen action of toremifene on hormone-dependent, independent and heterogeneous breast tumor growth in the athymic mouse. Cancer Res 1989; 49:1758–1762.

    PubMed  CAS  Google Scholar 

  14. Osborne CK, Jarman M, McCague R, Coronado EB, Hilsenbeck SG, Wakeling AE. The importance of tamoxifen metabolism in tamoxifen-stimulated breast tumor growth. Cancer Chemo Pharmacol 1994; 34:89–95.

    Article  CAS  Google Scholar 

  15. Kangas L. Review of the pharmacological properties of toremifene. J Steroid Biochem 1990; 36:191–195.

    Article  PubMed  CAS  Google Scholar 

  16. Kangas L. Biochemical and pharmacological effects of toremifene metabolites. Cancer Chemo Pharmacol 1990; 27:8–12.

    Article  CAS  Google Scholar 

  17. O’Regan RM, Cisneros A, England GM, MacGregor JI, Muenzner HD, Assikis V, et al. Growth characteristics of human endometrial cancer transplanted in athymic mice and treated with new antiestrogens, toremifene and ICI 182,780. J Natl Cancer Inst 1998; 90:1552–1558.

    Article  PubMed  Google Scholar 

  18. Hard GC, Iatropoulos MJ, Jordan K, Radi K, Kaltenberg OP, Imondi AR, Williams GM. Major differences in the hepatocarcinogenicity and DNA adduct forming ability between toremifene and tamoxifen in female Crl;CD (BR) rats. Cancer Res 1993; 53:4534–4541.

    PubMed  CAS  Google Scholar 

  19. Hirsimaki P, Hirsimaki Y, Nieminen L, Payne BJ. Tamoxifen induces hepatocellular carcinoma in rat liver: A 1 year study with 2 antiestrogens. Arch Toxicol 1993; 67:49–59.

    Article  PubMed  CAS  Google Scholar 

  20. Dragan YP, Vaughan J, Jordan VC, Pitot HC. Comparison of tamoxifen and toremifene on liver and kidney tumor promotion in female rats. Carcinogenesis 1995; 16:2733–2741.

    Article  PubMed  CAS  Google Scholar 

  21. Antilla M, Valvaara R, Kivinen S, Maanpaa J. Pharmacokinetics of toremifene. J Steroid Biochem 1990; 36:249–252.

    Article  Google Scholar 

  22. Jordan VC. Biochemical pharmacology of antiestrogen action. Pharmacol Rev 1984; 36:245–276.

    PubMed  CAS  Google Scholar 

  23. Wiebe VJ, Benz C, Shemano I, Cadman TB, DeGregorio MW. Pharmacokinetics of toremifene and its metabolites in patients with advanced breast cancer. Cancer Chemo Pharmacol 1990; 25:247–251.

    Article  CAS  Google Scholar 

  24. Webster LK, Crinis NA, Stokes KH, Bishop JF. High performance liquid chromatographic method for the determination of toremifene and its major human metabolites. J Chromatogr B Biomed Appl 1991; 565:482–487.

    Article  CAS  Google Scholar 

  25. Berthou F, Dreano Y. High performance liquid chromatographic analysis of tamoxifen, toremifene and their major human metabolites. J Chromatogr B Biomed Appl 1993; 616:117–127.

    Article  CAS  Google Scholar 

  26. Bishop J, Muray R, Webster L, Pitt P, Stokes K, Fennessy A, Olveri I, Leber G. Phase I clinical and pharmacokinetics study of high dose toremifene in postmenopausal patients with advanced breast cancer. Cancer Chemo Pharmacol 1992; 30:174–178.

    Article  CAS  Google Scholar 

  27. Kohler PC, Hamm JF, Wiebe VJ, DeGregorio MW, Shemano I, Tormey DC. Phase I study of the tolerance and pharmacokinetics of toremifene in patients with cancer. Breast Cancer Res Treat 1991; 16:19–26.

    Google Scholar 

  28. Hamm JT, Tormey DC, Kohler PC, Haller D, Green M, Shemano I. Phase I study of toremifene in patients with advanced cancer. J Clin Oncol 1991; 9:2036–2041.

    PubMed  CAS  Google Scholar 

  29. Tominga T, Abe O, Izuo M, Nomurga UT. A phase I study of toremifene. Breast Cancer Res Treat 1990; 16:27.

    Google Scholar 

  30. Valavaara R, Pyrhonen S, Heikkinen M, Rissanen P, Blanco G, Tholix E, et al. Toremifene, a new antiestrogenic treatment of advanced breast cancer Phase II study. Eur J Cancer 1988; 24:785–790.

    Article  CAS  Google Scholar 

  31. Valavaara R, Pyrhonen S. Low-dose toremifene in the treatment of estrogen receptor-positive advanced breast cancer in postmenopausal women. Curr Ther Res 1989; 46:966–973.

    Google Scholar 

  32. Valavaara R. Phase II experience with toremifene in the treatment of ER-positive breast cancer of postmenopausal women. Cancer Invest 1990; 8:275–276.

    Article  PubMed  CAS  Google Scholar 

  33. Gunderson S. Toremifene, a new antiestrogenic compound in the treatment of advanced breast cancer. Phase II study. Eur J Cancer 1990; 24A:785–790.

    Google Scholar 

  34. Hietanen T, Baltina D, Johansson R, Numminen S, Hakala T, Helle L, Valavaara R. High dose toremifene (240mg daily) is effective as first line hormonal treatment in advanced breast cancer: an ongoing phase II multicenter Finnish-Latvian cooperative study. Breast Cancer Res Treat 1990; 16:37–40.

    Article  Google Scholar 

  35. Modig H, Borgstrom M, Nilsson I, Westman G. Phase II clinical study of toremifene in patients with metastatic breast cancer. J Steroid Biochem 1990; 36:235–236.

    Article  PubMed  CAS  Google Scholar 

  36. Hayes DF, Van Zyl JA, Hacking A, Goedhals L, Bezwoda WR, Maillard JA, Jones SE, Vogel CL, Berus RF, Shemano I. Randomized comparison of tamoxifen and two separate doses of toremifene in postmenopausal patients with metastatic breast cancer. J Clin Oncol 1995; 113:2556–2566.

    Google Scholar 

  37. Konstantinova MM, Gershanovich ML. Results of comparative clinical evaluation of antiestrogens toremifene and tamoxifen in locally advanced and disseminated breast cancer [in Russian]. Vopr Onkol 1990; 36:1182–1186.

    PubMed  CAS  Google Scholar 

  38. Nomura Y, Tominaga T, Abe O, Izuo M, Ogawa N. Clinical evaluation of NK 22 (toremifene citrate) in advanced or recurrent breast cancer: a comparative study by a double blind method with tamoxifen [in Japanese]. Gan to Kagaku Ryoho 1993; 20:247–258.

    PubMed  CAS  Google Scholar 

  39. Stenbygaard LE, Herrstedt J, Thomsen JF, Svendsen KR, Engelholm SA, Dombernowsky P. Toremifene and tamoxifen in advanced breast cancer: a double-blind cross-over trial. Breast Cancer Res Treat 1993; 25:57–63.

    Article  PubMed  CAS  Google Scholar 

  40. Ebbs SR, Roberts J, Baum M. Response to toremifene (Fc-1157a) therapy in tamoxifen failed patients with breast cancer. Preliminary communication. J Steroid Biochem 1990; 36:239.

    Article  PubMed  CAS  Google Scholar 

  41. Hindy I, Juhos E, Szanto J, Szamel I. Effect of toremifene in breast cancer patients. Preliminary communication. J Steroid Biochem 1990; 36:225–226.

    Article  PubMed  CAS  Google Scholar 

  42. Jonsson PE, Malmberg M, Bergljung L, Ingvar C. Phase II study of high dose toremifene in advanced breast cancer progressing during tamoxifen treatment. Anticancer Res 1991; 11:873–876.

    PubMed  CAS  Google Scholar 

  43. Asaishi K, Tominaga T, Abe O, Izuo M, Nomula Y. Efficacy and safety of high dose NK 622 (toremifene citrate) in tamoxifen failed patients with breast cancer [in Japanese]. Gan to Kagaku Ryoho 1993; 20:91–99.

    PubMed  CAS  Google Scholar 

  44. Pyrrhonen S, Valavaara R, Vuorinen J, Hajba A. High dose toremifene in advanced breast cancer resistant to or relapsed during tamoxifen treatment. Breast Cancer Res Treat 1994; 29:223–228.

    Article  Google Scholar 

  45. Vogel CL, Shemano I, Schoenfelder J, Gams RA, Green MR. Multicenter phase II efficacy trial of toremifene in tamoxifen refractory patients with advanced breast cancer. J Clin Oncol 1993; 11:345–350.

    PubMed  CAS  Google Scholar 

  46. Perry JJ, Berry DA, Weiss RB, Hayes DM, Duggan DB, Henderson IC. High dose toremifene for estrogen and progesterone receptor negative metastatic breast cancer. A phase II trial of the Cancer and Leukemia Group B (CALGB). Breast Cancer Res Treat 1995; 36:35–40.

    Article  PubMed  CAS  Google Scholar 

  47. Saarto T, Blomquist C, Ehnholm C, Taskinen MR, Elomaa I. Antiatherogenic effects of adjuvant antiestrogens: A randomized trial comparing the effects of tamoxifen and toremifene on plasma lipid levels in postmenopausal women with node-positive breast cancer. J Clin Oncol 1996; 14:429–433.

    PubMed  CAS  Google Scholar 

  48. Roos WK, Oeze L, Loser R, Eppenberger U. Antiestrogen action of 3-hydroxytamoxifen in the human breast cancer cell line MCF-7f. J Natl Cancer Inst 1993; 71:55–59.

    Google Scholar 

  49. Loser R, Seibel K, Eppenberger U. No loss of estrogenic and antiestrogenic activity after demethylation of droloxifene (3-OH tamoxifen). Intl J Cancer 1985; 36:701–701.

    Article  CAS  Google Scholar 

  50. Loser R, Seibel K, Roos W, Eppenberger U. In vivo and in vitro antiestrogenic action of 3-hydroxytamoxifen, tamoxifen and 4-hydroxytamoxifen. Eur J Cancer Clin Oncol 1985; 21:900–985.

    Article  Google Scholar 

  51. Eppenberger U, Wosikowski K, Kung W. Pharmacologic and biologic properties of droloxifene, a new antiestrogen. Am J Clin Oncol 1991; 14:s5–s14.

    Article  PubMed  Google Scholar 

  52. Kawamura I, Mizota T, Lacey E, Tanaka Y, Manda T, Shimomura K, Kohsaka M. Pharmacologic and biologic properties of droloxifene, a new antiestrogen. Japn J Pharmacol 1993; 63:27–34.

    Article  CAS  Google Scholar 

  53. Hasman M, Rattel B, Loser R. Preclinical data for droloxifene. Cancer Lett 1994; 84:101–116.

    Article  Google Scholar 

  54. Wosikowski K, Kung W, Hasmann M, Loser R, Eppenberger U. Inhibition of growth factor activated proliferation by antiestrogens and effects of early gene expression of MCF-7 cells. Int J Cancer 1993; 53:290–297.

    Article  PubMed  CAS  Google Scholar 

  55. Ke HZ, Simmons HA, Pirie CM, Crawford DT, Thompson DD. Droloxifene, a new estrogen antagonist/agonist, prevents bone loss in ovariectomized rats. Endocrinology 1995; 136:2435–2441.

    Article  PubMed  CAS  Google Scholar 

  56. Kawamura I, Mizota T, Kondo N, Shimomura L, Kohsaka M. Antitumor effects of droloxifene, a new antiestrogen drug against 7,12 dimethyl (a) anthracene-induced mammary tumor in rats. Japn J Pharmacol 1991; 57:215–224.

    Article  CAS  Google Scholar 

  57. Winterfeld G, Hauff P, Grolich M, Arnold W, Fichtner I, Staab HJ. Investigations of droloxifene and other hormonal manipulations on N-nitrosomethlurea-induced rat mammary tumours. J Cancer Res Clin Oncol 1992; 119:91–96.

    Article  PubMed  CAS  Google Scholar 

  58. Grill HJ, Pollow K. Pharmacokinetics of droloxifene and its metabolites in breast cancer patients. Am J Clin Oncol 1991; 14:s21–s29.

    Article  PubMed  Google Scholar 

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

    Article  Google Scholar 

  60. Bellmunt J, Sole L. European early phase II dose finding study of droloxifene in advanced breast cancer. Am J Clin Oncol 1991; 14:536–539.

    Article  Google Scholar 

  61. Ahlemann LM, Staab HJ, Loser R, Seibel K, Huber HJ. Inhibition of growth of human cancer by intermittent exposure to the antiestrogen droloxifene. Tumor Diagn Ther 1988; 9:41–46.

    Google Scholar 

  62. Abe O, Enomote K, Fujiwara K, Izuo M, Iino Y, Tominaga T, et al. Phase I study of FK 435. Japn J Cancer Clin 1990; 36:903–913.

    CAS  Google Scholar 

  63. Abe O, Enomote K, Fugiwara K, Izumo M, Iino Y, Tominaga T, et al. Japanese early phase II study of droloxifene in the treatment of advanced bresat cancer. Am J Clin Oncol 1991; 14:540–541.

    Article  Google Scholar 

  64. Haarstad H, Gundersen S, Wist E, Raabe N, Mella O, Kvinnsland S. Droloxifene: a new anti-estrogen phase II study in advanced breast cancer. Acta Oncol 1992; 31:425–428.

    Article  PubMed  CAS  Google Scholar 

  65. Buzdar AU, Kau S, Hortobagyi GN, Theriault RL, Booser D, Holmes FA, et al. Phase I trial of droloxifene in patients with metastatic breast cancer. Cancer Chemother Pharmacol 1994; 33:313–316.

    Article  PubMed  CAS  Google Scholar 

  66. Chander SK, McCague R, Lugmani Y, Newton C, Dowsett M, Jarman M, Coombes RC. Pyrrolidino-4-iodotamoxifen and 4-iodotamoxifen, new analogues of the antiestrogen tamoxifen for the treatment of breast cancer. Cancer Res 1991; 51:5851–5858.

    PubMed  CAS  Google Scholar 

  67. McCague R, Parr IB, Haynes BP. Metabolism of the 4 iodo derivative of tamoxifen by isolated rat hepatocytes. Demonstration that the iodine atom reduces metabolic conversion and identification of four metabolites. Biochem Pharmacol 1990; 40:2277–2283.

    Article  PubMed  CAS  Google Scholar 

  68. White INH, deMatteis F, Davies A, Smith LL, Crofton-Sleigh C, Venitt S, Hewer A, Phillips DH. Genotoxic potential of tamoxifen and analogues in female Fischer 344/n rats, DBA/2 and C57BL/6 mice and human MCL-5 cells. Carcinogenesis 1992; 13:2197–2203.

    Article  PubMed  CAS  Google Scholar 

  69. Carnochan P, Trivedi M, Young H, Eccles S, Potter G, Haynes B, Ott R. Biodistribution and kinetics of pyrrolidino-4-iodotamoxifen and 4-iodotamoxifen, new analogues of the antiestrogen, tamoxifen, in the treatment of breast cancer. J Nuclear Biol Med 1994; 38:96–98.

    CAS  Google Scholar 

  70. Jordan VC, Gradishar WJ. Molecular mechanisms and future uses of antiestrogens. Mole Aspects Med 1997; 18:168–247.

    Google Scholar 

  71. Coombes RC, Haynes BP, Dowsett M, Quigley M, English J, Judson IR, Griggs LJ, Potter GA, McCague R, Jarman M. Idoxifene: report of a phase I study in patients with metastatic disease. Cancer Res 1995; 55:1070–1074.

    PubMed  CAS  Google Scholar 

  72. Black LJ, Jones CD, Falcone JF. Antagonism of estrogen action with a new benzothiophenederived antiestrogen. Life Sci 1983; 32:1031–1036.

    Article  PubMed  CAS  Google Scholar 

  73. Black LJ, Sato M, Rowley ER, Magee DE, Bekele A, Williams DC, et al. Raloxifene (LY 139481 HCL) prevents bone loss and reduces serum cholesterol without causing uterine hypertrophy in ovariectomized rats. J Clin Invest 1994; 93:63–69.

    Article  PubMed  CAS  Google Scholar 

  74. Jordan VC, Phelps E, Lindgren JU. Effects of antiestrogens on bone in castrated and intact female rats. Breast Cancer Res Treat 1987; 10:31–35.

    Article  PubMed  CAS  Google Scholar 

  75. Sato M, Kim J, Short LL, Szemenda CW, Bryant HU. Longitudinal and cross-setional analysis of raloxifene effects on tibiae from ovariectomized rats. J Pharmacol Exp Ther 1995; 272:1251–1259.

    Google Scholar 

  76. Scholl M, Huff KK, Lippman ME. Antiestrogenic effects of LY117018 in MCF-7 cells. Endocrinology 1983; 113:611–617.

    Article  PubMed  CAS  Google Scholar 

  77. Gottardis MM, Jordan VC. The antitumor action of keoxifene and tamoxifen in the N-nitrosomethylurea-induced rat mammary carcinoma model. Cancer Res 1987; 47:4020–4024.

    PubMed  CAS  Google Scholar 

  78. Gradishar W, Glusman J, Lu Y, Vogel C, Cohen FJ, Sledge GW, Jr. Effects of high dose raloxifene in selected patients with advanced breast carcinoma. Cancer 2000; 88:2047–2053.

    Article  PubMed  CAS  Google Scholar 

  79. Delmas PD, Bjarnason NH, Mitlak BH, Ravoux AC, Shah AS, Huster WJ, et al. Effects of raloxifene on bone mineral density, serum cholesterol concentrations, and uterine endometrium in postmenopausal women. N Engl J Med 1997; 337:1641–1647.

    Article  PubMed  CAS  Google Scholar 

  80. Jordan VC, Glusman JE, Eckert S, Lippman M, Powles T, Costa A, et al. Incident primary breast cancers are reduced by raloxifene: integrated data from multicenter, double-blind, randomized trials in ˜ 12,000 postmenopausal women. Proc ASCO Abs 1998; 466:122a.

    Google Scholar 

  81. Cummings SR, Eckert S, Krueger KA, Grady P, Poweles TJ, Cauley JA, et al. The effect of raloxifene on risk of breast cancer in postmenopausal women: results from the MORE randomized trial. Multiple Outcomes of Raloxifene Evaluation. JAMA 1999; 281:2189–2197.

    Article  PubMed  CAS  Google Scholar 

  82. Palkowitz AD, Glasebrook AL, Thrasher JK, Hauser KL, Short LL, Philips L, et al. Discovery and synthesis of [6-hydroxy-3-[4-(1-piperidinyl)-ethoxy-phenoxy]-2-(4-hydroxyphenyl) benzo[b]thiophene: a novel, highly potent selective estrogen receptor modulator (SERM). J Med Chem 1997; 40:1407–1416.

    Article  PubMed  CAS  Google Scholar 

  83. Bryant HU, Glasebrook AL, Knadler MP, Shetler PK, Short LL, Sato M, et al. LY 353,381.HCL: a highly potent, orally active selective estrogen receptor modulator. The Endocrine Society 79th Annual Meeting (Abstr.), 1997; 548:p3–446.

    Google Scholar 

  84. Sato M, Turner CH, Wang T, Dee Adrian M, Rowley E, Bryant HU. LY 353,381.HCL: A novel raloxifene analog with improved SERM potency and efficacy in vivo. J Pharmacol Exp Ther 1998; 287:1–7.

    PubMed  CAS  Google Scholar 

  85. Munster PN, Buzdar A, Dhingra K, Enas N, Ni L, Major M, et al. Phase I study of a third-generation selective estrogen receptor modulator, LY353381.HCI, in metastatic breast cancer. J Clin Oncol 2001; 19,7:2002–2009.

    Google Scholar 

  86. Simard J, Labrie C, Belanger A, Gauthier S, Singh SM, Merand Y, Labrie F. Characterization of the effects of the novel non-steroidal antiestrogen EM-800 on basal and estrogeninduced proliferation of T-47D, ZR-75-1 and MCF-7 human breast cancer cells in vitro. Intl J Cancer 1997; 73:104–112.

    Article  CAS  Google Scholar 

  87. Couillard S, Gutman M, Labrie C, Belanger A, Candas B, Labrie F. Comparison of the effects of the antiestrogens EM-800 and tamoxifen on the growth of human breast ZR-75-1 cancer xenografts in nude mice. Cancer Res 1998; 58:60–64.

    PubMed  CAS  Google Scholar 

  88. Luo S, Stojanovic M, Labrie C, Labrie F. Inhibitory effect of the novel antiestrogen EM-800 and medroxyprogesterone acetate on estrone-stimulated growth of dimethylbenz[a]anthraceneinduced mammary carcinoma in rats. Intl J Cancer 1997; 3:580–586.

    Article  Google Scholar 

  89. Luo S, Sourla A, Labrie C, Gauthier S, Meraud Y, Belanger A, Labrie F. Effect of twentyfour-week treatment with the antiestrogen EM-800 on estrogen-sensitive parameters in intact and ovariectomized mice. Endocrinology 1998; 139:2645–2656.

    Article  PubMed  CAS  Google Scholar 

  90. Wakeling AE, Dukes M, Bowler J. A potent specific pure antiestrogen with clinical potential. J Endocrinol 1991; 99:455–464.

    Article  Google Scholar 

  91. Dauvois S, Danielian PS, White R, Parker MG. Antiestrogen ICI 164,384 reduces cellular estrogen receptor by increasing its turnover. Proc Natl Acad Sci USA 1992; 89:4037–4041.

    Article  PubMed  CAS  Google Scholar 

  92. Gibson MK, Nemmers LA, Beckman WC, Davis VL, Curtis SW, Korach KS. The mechanism of ICI 164, 384 antiestrogenicity involves rapid loss of estrogen receptor in uterine tissue. Endocrinology 1991; 129:2000–2010.

    Article  PubMed  CAS  Google Scholar 

  93. Thompson EW, Katz D, Shima TB, Wakeling AE, Lipman ME, Dickson RB. ICI 164, 384, a pure antagonist of estrogen stimulated MCF-7 cell proliferation and invasiveness. Cancer Res 1989; 49:6929–6934.

    PubMed  CAS  Google Scholar 

  94. Osborne CK, Coronado EB, Robinson JP. Human breast cancer in athymic nude mice: cytostatic effects of long-term antiestrogenic activity. Eur J Cancer 1987; 23:1189–1196.

    Article  CAS  Google Scholar 

  95. Osborne CK, Coronado-Heinsohn EB, Hilsenbeck SG, McCue BL, Wakeling AE, McClelland RA, et al. Comparison of the effects of a pure steroidal aniestrogen with those of tamoxifen in a model of human cancer. J Natl Cancer Inst 1995; 87:746–750.

    Article  PubMed  CAS  Google Scholar 

  96. Nicholson RI, Walker KJ, Bouzukar N, Wills RJ, Gee JM, Rushmere NK, Davies P. Estrogen deprivation in breast cancer. Clinical, experimental and biological aspects. Ann NY Acad Sci 1990; 595:316–327.

    Article  PubMed  CAS  Google Scholar 

  97. Gallagher A, Chambers TJ, Tobias JH. The estrogen antagonist ICI 182,780 reduces cancellous bone volumes in female rats. Endocrinology 1993; 133:2787–2791.

    Article  PubMed  CAS  Google Scholar 

  98. Howell A, DeFriend D, Robertson J, Blamey R, Walton P (1995). Response to a specific antiestrogen (ICI 182780) in tamoxifen-resistant breast cancer. Lancet 1995; 345:29–30.

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Division of Hematology/Oncology, Department of Medicine, Northwestern University Medical Program, The Robert H. Lurie Comprehensive Cancer Center, Chicago, IL

    Ruth M. O’Regan & William J. Gradishar

Authors
  1. Ruth M. O’Regan
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. William J. Gradishar
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Lombardi Comprehensive Cancer Center, Georgetown University, 3970 Reservoir Rd. NW Research Bldg. E501, Washington, DC, 20057, USA

    V. Craig Jordan

  2. AstraZeneca Pharmaceuticals Zeneca Pharmaceutical, Alderly Park, Alderly House, Macclesfield, SK 10 4TF, UK

    Barrington J.A. Furr

Rights and permissions

Reprints and permissions

Copyright information

© 2009 Humana Press, a part of Springer Science+Business Media, LLC

About this chapter

Cite this chapter

O’Regan, R.M., Gradishar, W.J. (2009). Clinical Utility of New Antiestrogens. In: Jordan, V.C., Furr, B.J. (eds) Hormone Therapy in Breast and Prostate Cancer. Cancer Drug Discovery and Development. Humana Press. https://doi.org/10.1007/978-1-59259-152-7_9

Download citation

  • DOI: https://doi.org/10.1007/978-1-59259-152-7_9

  • Publisher Name: Humana Press

  • Print ISBN: 978-1-60761-471-5

  • Online ISBN: 978-1-59259-152-7

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation