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Selective Estrogen Receptor Modulators pp 141–157Cite as

Pure Antiestrogens

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References

  1. Addo S, Yates RA, Laight A (2002) A phase I trial to assess the pharmacology of the new oestrogen receptor antagonist fulvestrant on the endometrium in healthy postmenopausal volunteers. Br J Cancer 87:1354–1359

    Article  PubMed  CAS  Google Scholar 

  2. Ameller T, Marsaud V, Legrand P, Gref R, Renoir JM (2004) Pure antiestrogen RU 58668-loaded nanospheres: morphology, cell activity and toxicity studies. Eur J Pharm Sci 21:361–370

    Article  PubMed  CAS  Google Scholar 

  3. Baker VL, Jaffe RB (1996) Clinical uses of antiestrogens. Obstet Gynecol Surv 51:45–59

    Article  PubMed  CAS  Google Scholar 

  4. Barkhem T, Carlsson B, Nilsson Y, Enmark E, Gustafsson J, Nilsson S (1998) Differential response of estrogen receptor alpha and estrogen receptor beta to partial estrogen agonists/antagonists. Mol Pharmacol 54:105–112

    PubMed  CAS  Google Scholar 

  5. Barsalou A, Gao W, Anghel SI, Carriere J, Mader S (1998) Estrogen response elements can mediate agonist activity of anti-estrogens in human endometrial Ishikawa cells. J Biol Chem 273:17138–17146

    Article  PubMed  CAS  Google Scholar 

  6. Bross PF, Baird A, Chen G, Jee JM, Lostritto RT, Morse DE, Rosario LA, Williams GM, Yang P, Rahman A, et al. (2003) Fulvestrant in postmenopausal women with advanced breast cancer. Clin Cancer Res 9:4309–4317

    PubMed  CAS  Google Scholar 

  7. Bross PF, Cohen MH, Williams GA, Pazdur R (2002) FDA drug approval summaries: fulvestrant. Oncologist 7:477–480

    Article  PubMed  CAS  Google Scholar 

  8. Bryant HU, Dere WH (1998) Selective estrogen receptor modulators: an alternative to hormone replacement therapy. Proc Soc Exp Biol Med 217:45–52

    PubMed  CAS  Google Scholar 

  9. Brzozowski AM, Pike AC, Dauter Z, Hubbard RE, Bonn T, Engstrom O, Ohman L, Greene GL, Gustafsson JA, Carlquist M (1997) Molecular basis of agonism and antagonism in the oestrogen receptor. Nature 389:753–758

    Article  PubMed  CAS  Google Scholar 

  10. Cathapermal S, Lavigne MC, Leong-Son M, Alibadi T, Ramwell PW (1998) Stereoisomer-specific inhibition of superoxide anion-induced rat aortic smooth-muscle cell proliferation by 17beta-estradiol is estrogen receptor dependent. J Cardiovasc Pharmacol 31:499–505

    Article  PubMed  CAS  Google Scholar 

  11. Dauvois S, White R, Parker MG (1993) The antiestrogen ICI 182780 disrupts estrogen receptor nucleocytoplasmic shuttling. J Cell Sci 106:1377–1388

    PubMed  CAS  Google Scholar 

  12. DeFriend DJ, Howell A, Nicholson RI, Anderson E, Dowsett M, Mansel RE, Blamey RW, Bundred NJ, Robertson JF, Saunders C, et al. (1994) Investigation of a new pure antiestrogen (ICI 182780) in women with primary breast cancer. Cancer Res 54:408–414

    PubMed  CAS  Google Scholar 

  13. Devin-Leclerc J, Meng X, Delahaye F, Leclerc P, Baulieu EE, Catelli MG(1998) Interaction and dissociation by ligands of estrogen receptor and Hsp90: the antiestrogen RU 58668 induces a protein synthesis-dependent clustering of the receptor in the cytoplasm. Mol Endocrinol 12:842–854

    Article  PubMed  CAS  Google Scholar 

  14. Doualla-Bell F, Bonneau MJ, Labrie F, Fortier MA (1995) Differential effects of a steroidal antiestrogen, EM-139, on prostaglandin and cyclic adenosine 3′,5′-monophosphate production in the circular and longitudinal layers of bovine myometrium. Biol Reprod 52:1358–1363

    Article  PubMed  CAS  Google Scholar 

  15. Dowsett M, Howell R, Salter J, Thomas NM, Thomas EJ (1995) Effects of the pure antioestrogen ICI 182780 on oestrogen receptors, progesterone receptors and Ki67 antigen in human endometrium in vivo. Hum Reprod 10:262–267

    PubMed  CAS  Google Scholar 

  16. Dukes M, Miller D, Wakeling AE, Waterton JC (1992) Antiuterotrophic effects of a pure antioestrogen, ICI 182,780: magnetic resonance imaging of the uterus in ovariectomized monkeys. J Endocrinol 135:239–247

    PubMed  CAS  Google Scholar 

  17. Dukes M, Waterton JC, Wakeling AE (1993) Antiuterotrophic effects of the pure antioestrogen ICI 182,780 in adult female monkeys (Macaca nemestrina): quantitative magnetic resonance imaging. J Endocrinol 138:203–210

    PubMed  CAS  Google Scholar 

  18. Fawell SE, White R, Hoare S, Sydenham M, Page M, Parker MG (1990) Inhibition of estrogen receptor-DNA binding by the “pure” antiestrogen ICI 164,384 appears to be mediated by impaired receptor dimerization. Proc Natl Acad Sci USA 87:6883–6887

    Article  PubMed  CAS  Google Scholar 

  19. Frasor J, Stossi F, Danes JM, Komm B, Lyttle CR, Katzenellenbogen BS (2004) Selective estrogen receptor modulators: discrimination of agonistic versus antagonistic activities by gene expression profiling in breast cancer cells. Cancer Res 64:1522–1533

    Article  PubMed  CAS  Google Scholar 

  20. Gallagher A, Chambers TJ, Tobias JH (1993) The estrogen antagonist ICI 182,780 reduces cancellous bone volume in female rats. Endocrinology 133:2787–2791

    Article  PubMed  CAS  Google Scholar 

  21. Gottardis MM, Ricchio ME, Satyaswaroop PG, Jordan VC (1990) Effect of steroidal and nonsteroidal antiestrogens on the growth of a tamoxifen-stimulated human endometrial carcinoma (EnCa101) in athymic mice. Cancer Res 50:3189–3192

    PubMed  CAS  Google Scholar 

  22. Gradishar WJ, Jordan VC (1997) Clinical potential of new antiestrogens. J Clin Oncol 15:840–852

    PubMed  CAS  Google Scholar 

  23. Hegele-Hartung C, Fritzemeier KH, Diel P (1997) Effects of a pure antiestrogen and progesterone on estrogen-mediated alterations of blood flow and progesterone receptor expression in the aorta of ovariectomized rabbits. J Steroid BioChem Mol Biol 63:237–249

    Article  PubMed  CAS  Google Scholar 

  24. Hoffmann J, Bohlmann R, Heinrich N, Hofmeister H, Kroll J, Kunzer H, Lichtner RB, Nishino Y, Parczyk K, Sauer G, et al. (2004) Characterization of new estrogen receptor destabilizing compounds: effects on estrogen-sensitive and tamoxifen-resistant breast cancer. J Natl Cancer Inst 96:210–218

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  26. Howell A, DeFriend DJ, Robertson JF, Blamey RW, Anderson L, Anderson E, Sutcliffe FA, Walton P (1996) Pharmacokinetics, pharmacological and anti-tumour effects of the specific anti-oestrogen ICI 182780 in women with advanced breast cancer. Br J Cancer 74:300–308

    PubMed  CAS  Google Scholar 

  27. Howell A, Robertson JF, Quaresma AJ, Aschermannova A, Mauriac L, Kleeberg UR, Vergote I, Erikstein B, Webster A, Morris C (2002) Fulvestrant, formerly ICI 182,780, is as effective as anastrozole in postmenopausal women with advanced breast cancer progressing after prior endocrine treatment. J Clin Oncol 20:3396–3403

    Article  PubMed  CAS  Google Scholar 

  28. Howell A, Robertson JFR, Abram P, Lichinitser MR, Elledge R, Bajetta E, Watanabe T, Morris C, Webster A, Dimery I, et al. (2004a) Comparison of fulvestrant versus tamoxifen for the treatment of advanced breast cancer in postmenopausal women previously untreated with endocrine therapy: a multinational, double-blind, randomized trial. J Clin Oncol 22:1605–1613

    Article  PubMed  CAS  Google Scholar 

  29. Howell SJ, Johnston SRD, Howell A (2004b) The use of selective estrogen receptor modulators and selective estrogen receptor down-regulators in breast cancer. Best Pract Res Clin Endocrinol Metab 18:47–66

    Article  PubMed  CAS  Google Scholar 

  30. Huynh H, Nickerson T, Pollak M, Yang X (1996) Regulation of insulin-like growth factor I receptor expression by the pure antiestrogen ICI 182780. Clin Cancer Res 2:2037–2042

    PubMed  CAS  Google Scholar 

  31. Jensen EV, Khan SA (2004) A two-site model for antiestrogen action. Mech Age Develop 125:679–682

    Article  CAS  Google Scholar 

  32. Jiang SY, Langan-Fahey SM, Stella AL, McCague R, Jordan VC (1992) Point mutation of estrogen receptor (ER) in the ligand-binding domain changes the pharmacology of antiestrogens in ER-negative breast cancer cells stably expressing complementary DNAs for ER. Mol Endocrinol 6:2167–2174

    Article  PubMed  CAS  Google Scholar 

  33. Johnston S (2004) Fulvestrant and the sequential endocrine cascade for advanced breast cancer. Br J Cancer 90(Suppl 1):S15–S18

    Article  PubMed  CAS  Google Scholar 

  34. Johnston SR, Lu B, Dowsett M, Liang X, Kaufmann M, Scott GK, Osborne CK, Benz CC (1997) Comparison of estrogen receptor DNA binding in untreated and acquired antiestrogen-resistant human breast tumors. Cancer Res 57:3723–3727

    PubMed  CAS  Google Scholar 

  35. Jordan VC (1993) A current view of tamoxifen for the treatment and prevention of breast cancer. Br J Pharmacol 110:507–517

    PubMed  CAS  Google Scholar 

  36. Kassem M, Okazaki R, Harris SA, Spelsberg TC, Conover CA, Riggs BL (1998) Estrogen effects on insulin-like growth factor gene expression in a human osteoblastic cell line with high levels of estrogen receptor. Calcif Tissue Int 62:60–66

    Article  PubMed  CAS  Google Scholar 

  37. Li S, Levesque C, Geng CS, Yan X, Labrie F (1995) Inhibitory effects of medroxyprogesterone acetate (MPA) and the pure antiestrogen EM-219 on estrone (E1)-stimulated growth of dimethylbenz(a)anthracene (DMBA)-induced mammary carcinoma in the rat. Breast Cancer Res Treat 34:147–159

    Article  PubMed  CAS  Google Scholar 

  38. Lim KB, Ng CY, Ong CK, Ong CS, Tran E, Nguyen TT, Chan GM, Huynh H (2001) Induction of apoptosis in mammary gland by a pure anti-estrogen ICI 182780. Breast Cancer Res Treat 68:127–138

    Article  PubMed  CAS  Google Scholar 

  39. Lonard DM, Smith CL (2002) Molecular perspectives on selective estrogen receptor modulators (SERMs): progress in understanding their tissue-specific agonist and antagonist actions. Steroids 67:15–24

    Article  PubMed  CAS  Google Scholar 

  40. Long BJ, Tilghman SL, Yue W, Thiantanawat A, Grigoryev DN, Brodie AM (1998) The steroidal antiestrogen ICI 182,780 is an inhibitor of cellular aromatase activity. J Steroid BioChem Mol Biol 67:293–304

    Article  PubMed  CAS  Google Scholar 

  41. Love RR, Newcomb PA, Wiebe DA, Surawicz TS, Jordan VC, Carbone PP, DeMets DL (1990) Effects of tamoxifen therapy on lipid and lipoprotein levels in postmenopausal patients with node-negative breast cancer. J Natl Cancer Inst 82:1327–1332

    PubMed  CAS  Google Scholar 

  42. Lundeen SG, Carver JM, McKean ML, Winneker RC (1997) Characterization of the ovariectomized rat model for the evaluation of estrogen effects on plasma cholesterol levels. Endocrinology 138:1552–1558

    Article  PubMed  CAS  Google Scholar 

  43. MacGregor JI, Jordan VC (1998) Basic guide to the mechanisms of antiestrogen action. Pharmacol Rev 50:151–196

    PubMed  CAS  Google Scholar 

  44. McClelland RA, Gee JM, Francis AB, Robertson JF, Blamey RW, Wakeling AE, Nicholson RI (1996) Short-term effects of pure anti-oestrogen ICI 182780 treatment on oestrogen receptor, epidermal growth factor receptor and transforming growth factor-alpha protein expression in human breast cancer. Eur J Cancer 32A: 413–416

    Article  PubMed  CAS  Google Scholar 

  45. Morris C, Wakeling A (2002) Fulvestrant (‘Faslodex’)-a new treatment option for patients progressing on prior endocrine therapy. Endocr Relat Cancer 9:267–276

    Article  PubMed  CAS  Google Scholar 

  46. Nawaz Z, Stancel GM, Hyder SM (1999) The pure antiestrogen ICI 182,780 inhibits progestin-induced transcription. Cancer Res 59:372–376

    PubMed  CAS  Google Scholar 

  47. Osborne CK, Coronado E, Allred DC, Wiebe V, DeGregorio M (1991)Acquired tamoxifen resistance: correlation with reduced breast tumor levels of tamoxifen and isomerization of trans-4-hydroxytamoxifen. J Natl Cancer Inst 83:1477–1482

    PubMed  CAS  Google Scholar 

  48. Osborne CK, Pippen J, Jones SE, Parker LM, Ellis M, Come S, Gertler SZ, May JT, Burton G, Dimery I, et al. (2002) Double-blind, randomized trial comparing the efficacy and tolerability of fulvestrant versus anastrozole in postmenopausal women with advanced breast cancer progressing on prior endocrine therapy: results of a North American trial. J Clin Oncol 20:3386–3395

    Article  PubMed  CAS  Google Scholar 

  49. Osipo C, Liu H, Meeke K, Jordan VC (2004) The consequences of exhaustive antiestrogen therapy in breast cancer: estrogen-induced tumor cell death. Exp Biol Med 229: 722–731

    CAS  Google Scholar 

  50. Pike AC, Brzozowski AM, Walton J, Hubbard RE, Thorsell AG, Li YL, Gustafsson JA, Carlquist M (2001) Structural insights into the mode of action of a pure antiestrogen. Structure 9:145–153

    Article  PubMed  CAS  Google Scholar 

  51. Pink JJ, Jordan VC (1996) Models of estrogen receptor regulation by estrogens and antiestrogens in breast cancer cell lines. Cancer Res 56:2321–2330

    PubMed  CAS  Google Scholar 

  52. Robertson JF, Harrison M (2004) Fulvestrant: pharmacokinetics and pharmacology. Br J Cancer 90(Suppl 1):S7–10

    Article  PubMed  CAS  Google Scholar 

  53. Robertson JF, Harrison MP (2003) Equivalent single-dose pharmacokinetics of two different dosing methods of prolonged-release fulvestrant (‘Faslodex’) in postmenopausal women with advanced breast cancer. Cancer Chemother Pharmacol 52:346–348

    Article  PubMed  CAS  Google Scholar 

  54. Robertson JF, Osborne CK, Howell A, Jones SE, Mauriac L, Ellis M, Kleeberg UR, Come SE, Vergote I, Gertler S, et al. (2003) Fulvestrant versus anastrozole for the treatment of advanced breast carcinoma in postmenopausal women: a prospective combined analysis of two multicenter trials. Cancer 98:229–238

    Article  PubMed  CAS  Google Scholar 

  55. Robertson JFR (2004) Selective oestrogen receptor modulators/new antioestrogens: a clinical perspective. Cancer Treat Rev 30:695–706

    Article  PubMed  CAS  Google Scholar 

  56. Robertson JFR, Come SE, Jones SE, Beex L, Kaufmann M, Makris A, Nortier JWR, Possinger K, Rutqvist LE (2005) Endocrine treatment options for advanced breast cancer — the role of fulvestrant. Eur J Cancer 41:346–356

    Article  PubMed  CAS  Google Scholar 

  57. Sakai F, Cheix F, Clavel M, Colon J, Mayer M, Pommatau E, Saez S (1978) Increases in steroid binding globulins induced by tamoxifen in patients with carcinoma of the breast. J Endocrinol 76:219–226

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  60. Sourla A, Luo S, Labrie C, Belanger A, Labrie F (1997) Morphological changes induced by 6-month treatment of intact and ovariectomized mice with tamoxifen and the pure antiestrogen EM-800. Endocrinology 138:5605–5617

    Article  PubMed  CAS  Google Scholar 

  61. Thomas EJ, Walton PL, Thomas NM, Dowsett M (1994) The effects of ICI 182,780, a pure anti-oestrogen, on the hypothalamic-pituitary-gonadal axis and on endometrial proliferation in pre-menopausal women. Hum Reprod 9:1991–1996

    PubMed  CAS  Google Scholar 

  62. Tong GM, Rajah TT, Zang XP, Pento JT (2002) The effect of antiestrogens on TGF-beta-mediated chemotaxis of human breast cancer cells. Anticancer Res 22:103–106

    PubMed  CAS  Google Scholar 

  63. van Bezooijen RL, Que I, Ederveen AG, Kloosterboer HJ, Papapoulos SE, Lowik CW (1998) Plasma nitrate + nitrite levels are regulated by ovarian steroids but do not correlate with trabecular bone mineral density in rats. J Endocrinol 159:27–34

    Article  PubMed  Google Scholar 

  64. Van de Velde P, Nique F, Bouchoux F, Bremaud J, Hameau MC, Lucas D, Moratille C, Viet S, Philibert D, Teutsch G (1994) RU 58 668, a new pure antiestrogen inducing a regression of human mammary carcinoma implanted in nude mice. J Steroid Bio Chem Mol Biol 48:187–196

    Article  Google Scholar 

  65. Van de Velde P, Nique F, Bremaud J, Hameau MC, Philibert D, Teutsch G (1995) Exploration of the therapeutic potential of the antiestrogen RU 58668 in breast cancer treatment. Ann NY Acad Sci 761:164–175

    PubMed  Google Scholar 

  66. Van de Velde P, Nique F, Planchon P, Prevost G, Bremaud J, Hameau MC, Magnien V, Philibert D, Teutsch G (1996) RU 58668: further in vitro and in vivo pharmacological data related to its antitumoral activity. J Steroid BioChem Mol Biol 59:449–457

    Article  PubMed  Google Scholar 

  67. Wakeling AE (2000) Similarities and distinctions in the mode of action of different classes of antioestrogens. Endocr Relat Cancer 7:17–28

    Article  PubMed  CAS  Google Scholar 

  68. Wakeling AE, Bowler J (1987) Steroidal pure antioestrogens. J Endocrinol 112:R7–10

    Article  PubMed  CAS  Google Scholar 

  69. Wakeling AE, Dukes M, Bowler J (1991) A potent specific pure antiestrogen with clinical potential. Cancer Res 51:3867–3873

    PubMed  CAS  Google Scholar 

  70. Wakeling AE, Newboult E, Peters SW(1989) Effects of antioestrogens on the proliferation of MCF-7 human breast cancer cells. J Mol Endocrinol 2:225–234

    PubMed  CAS  Google Scholar 

  71. Wijayaratne AL, McDonnell DP (2001) The human estrogen receptor-alpha is a ubiquitinated protein whose stability is affected differentially by agonists, antagonists, and selective estrogen receptor modulators. J Biol Chem 276:35684–35692

    Article  PubMed  CAS  Google Scholar 

  72. Willis KJ, London DR, Ward HW, Butt WR, Lynch SS, Rudd BT (1977) Recurrent breast cancer treated with the antioestrogen tamoxifen: correlation between hormonal changes and clinical course. Br Med J 1:425–428

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Research Unit, Hospital Clínico Universitario of Valencia, Valencia, Spain

    Carlos Hermenegildo

  2. Unidad Central de Investigación, School of Medicine and Dentistry, University of Valencia, Avda. Blasco Ibañez, 17, 46010, Valencia, Spain

    Carlos Hermenegildo

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  1. Carlos Hermenegildo
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Editors and Affiliations

  1. Department of Pediatrics Obstetrics and Gynecology School of Medicine, University of Valencia, Valencia, Spain

    Antonio Cano Sanchez

  2. Servei d’Obstetricia i Ginecologia, Hospital de la Santa Creu i Sant Pau, C/ Sant Antoni M. Claret 167, 08025, Barcelona

    Joaquim Calaf i Alsina

  3. Department of Obstetrics and Gynaecology, Hospital Universitario Virgen Macarena, School of Medicine University of Sevilla, Sevilla, Spain

    José-Luis Dueñas-Díez

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Hermenegildo, C. (2006). Pure Antiestrogens. In: Sanchez, A.C., Calaf i Alsina, J., Dueñas-Díez, JL. (eds) Selective Estrogen Receptor Modulators. Springer, Berlin, Heidelberg . https://doi.org/10.1007/3-540-34742-9_6

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