Hormone therapy for breast cancer, with an emphasis on the pure antiestrogen fulvestrant : mode of action, antitumor efficacy and effects on bone health
[en] Breast cancer is a major health problem in women of developed Western countries. Whereas estrogen receptor (ER) may be involved in many cases in breast carcinogenesis, its expression in breast tumors may predict a favorable response to hormone therapy. In this review, we report the role played by ER in breast cancer and compare the effects and mechanisms of action of partial (tamoxifen) and pure (fulvestrant) antiestrogens, as well as of aromatase inhibitors. Moreover, as ER also has a critical role in bone metabolism, we review the beneficial and adverse effects of breast cancer hormone therapy on bone health, with a particular emphasis on fulvestrant, the only pure antiestrogen recently approved by the FDA for Phase III clinical trials. We conclude that, because of its therapeutic efficacy and its seemingly minimal effect on bone integrity, fulvestrant represents a new option for the hormonal treatment of breast cancer that deserves further clinical evaluation.
Disciplines :
Immunology & infectious disease Oncology
Author, co-author :
Journé, Fabrice
Body, Jean-Jacques
Leclercq, Guy
Laurent, Guy ; Université de Mons > Faculté de Médecine et de Pharmacie > Histologie
Language :
English
Title :
Hormone therapy for breast cancer, with an emphasis on the pure antiestrogen fulvestrant : mode of action, antitumor efficacy and effects on bone health
Beatson GT. On the treatment of inoperable cases of carcinoma of the mamma: suggestions for a new method of treatment, with illustrative cases. Lancet 1896;148:104-7
Jensen EV. Mechanism of estrogen action in relation to carcinogenesis. Proc Can Cancer Conf 1966;6:143-65
Green S, Walter P, Kumar V, et al. Human oestrogen receptor cDNA: sequence, expression and homology to v-erb-A. Nature 1986;320:134-9
Kuiper GG, Enmark E, Pelto-Huikko M, et al. Cloning of a novel receptor expressed in rat prostate and ovary. Proc Natl Acad Sci USA 1996;93:5925-30.
Mosselman S, Polman J, Dijkema R. ER beta: identification and characterization of a novel human estrogen receptor. FEBS Lett 1996;392:49-53
Germain P, Staels B, Dacquet C, et al. Overview of nomenclature of nuclear receptors. Pharmacol Rev 2006;58:685-704
Ascenzi P, Bocedi A, Marino M. Structure-function relationship of ERα and beta: impact on human health. Mol Aspects Med 2006; 27:299-402
Hall JM, McDonnell DP. Coregulators in nuclear estrogen receptor action: from concept to therapeutic targeting. Mol Interv 2005;5:343-57
Lonard DM, O'Malley BW. Expanding functional diversity of the coactivators. Trends Biochem Sci 2005;30:126-32
Riggins RB, Schrecengost RS, Guerrero MS, Bouton AH. Pathways to tamoxifen resistance. Cancer Lett 2007;256:1-24
Bjornstrom L, Sjoberg M. Mechanisms of estrogen receptor signaling: convergence of genomic and nongenomic actions on target genes. Mol Endocrinol (Baltimore) 2005;19:833-42
Levin ER, Pietras RJ. Estrogen receptors outside the nucleus in breast cancer. Breast Cancer Res Treat 2008;108(3):351-61
Stossi F, Barnett DH, Frasor J, et al. Transcriptional profiling of estrogen-regulated gene expression via estrogen receptor (ER) alpha or ERbeta in human osteasarcoma cells: distinct and common target genes for these receptors. Endocrinology 2004;145:3473-86
Speirs V, Carder PJ, Lane S, et al. Oestrogen receptor beta: what it means for patients with breast cancer. Lancet Oncol 2004;5:174-81
Bardin A, Boulle N, Lazennec G, et al. Loss of ERbeta expression as a common step in estrogen-dependent tumor progression. Endocr Relat Cancer 2004;11:537-51
Journé F, Body JJ, Leclercq G, et al. Estrogen responsiveness of IBEP-2, a new human cell line derived from breast carcinoma. Breast Cancer Res Treat 2004;86:39-53
Cheang MC, Treaba DO, Speers CH, et al. Immunohistochemical detection using the new rabbit monoclonal antibody SP1 of estrogen receptor in breast cancer is superior to mouse monoclonal antibody 1D5 in predicting survival. J Clin Oncol 2006;24:5637-44
Dunnwald LK, Rossing MA, Li CI. Hormone receptor status, tumor characteristics, and prognosis: a prospective cohort of breast cancer patients. Breast Cancer Res 2007;9:R6
Allred DC, Harvey JM, Berardo M, Clark GM. Prognostic and predictive factors in breast cancer by immunohistochemical analysis. Mod Pathol 1998;11:155-68
Wells CA, Sloane JP, Coleman D, et al. Consistency of staining and reporting of oestrogen receptor immunocytochemistry within the European Union: an inter-laboratory study. Virchows Arch 2004;445:119-28
Jensen EV, Block GE, Smith S, et al. Estrogen receptors and breast cancer response to adrenalectomy. Natl Cancer Inst Monogr 1971;34:55-70
Jordan VC. The development of tamoxifen for breast cancer therapy: a tribute to the late Arthur L Walpole. Breast Cancer Res Treat 1988;11:197-209
Jensen EV, Jordan VC. The estrogen receptor: a model for molecular medicine. Clin Cancer Res 2003;9:1980-9
Shiau AK, Barstad D, Loria PM, et al. The structural basis of estrogen receptor/coactivator recognition and the antagonism of this interaction by tamoxifen. Cell 1998;95:927-37
Webb P, Lopez GN, Uht RM, Kushner PJ. Tamoxifen activation of the estrogen receptor/AP-1 pathway: potential origin for the cell-specific estrogen-like effects of antiestrogens. Mol Endocrinol (Baltimore) 1995;9:443-56
Khan S, Abdelrahim M, Samudio I, Safe S. Estrogen receptor/Sp1 complexes are required for induction of cad gene expression by 17beta-estradiol in breast cancer cells. Endocrinology 2003;144:2325-35
EBCTCG. Tamoxifen for early breast cancer: an overview of the randomised trials. Early Breast Cancer Trialists' Collaborative Group. Lancet 1998;351:1451-67
EBCTCG. Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomised trials. Lancet 2005;365:1687-717
Bernstein L, Deapen D, Cerhan JR, et al. Tamoxifen therapy for breast cancer and endometria] cancer risk. J Natl Cancer Inst 1999;91:1654-62
Howell SJ, Johnston SR, Howell A. The use of selective estrogen receptor modulators and selective estrogen receptor down-regulators in breast cancer. Best Pract Res Clin Endocrinol Metab 2004;18:47-66
Jones CD, Suarez T, Massey EH, et al. Synthesis and antiestrogenic activity of [3,4-dihydro-2-(4-methoxyphenyl)-1-naphthalenyl] [4-[2-(1-pyrrolidinyl)ethoxy]-phenyl]methanone, methanesulfonic acid salt. J Med Chem 1979;22:962-6
Black LJ, Sato M, Rowley ER, et al. Raloxifene (LY139481 HCI) prevents bone loss and reduces serum cholesterol without causing uterine hypertrophy in ovariectomized rats. J Clin Invest 1994;93:63-9
Black LJ, Jones CD, Falcone JF. Antagonism of estrogen action with a new benzothiophene derived antiestrogen. Life Sci 1983;32:1031-6
Buzdar AU, Marcus C, Holmes F, et al. Phase II evaluation of Ly156758 in metastatic breast cancer. Oncology 1988;45:344-5
Massarweh S, Schiff R. Unraveling the mechanisms of endocrine resistance in breast cancer: new therapeutic opportunities. Clin Cancer Res 2007;13:1950-4
Jordan VC, Osipo C, Schafer JM, et al. Changing role of the oestrogen receptor in the life and death of breast cancer cells. Breast (Edinburgh) 2003;12:432-41
Howell A, Osborne CK, Morris C, Wakeling AE. ICI 182,780 (Faslodex): development of a novel, 'pure' antiestrogen. Cancer 2000;89:817-25
Howell A. Pure oestrogen antagonists for the treatment of advanced breast cancer. Endocr Rel Cancer 2006;13:689-706
Wakeling AE, Dukes M, Bowler J. A potent specific pure antiestrogen with clinical potential. Cancer Res 1991;51:3867-73
DeFriend DJ, Howell A, Nicholson RI, et al. Investigation of a new pure antiestrogen (ICI 182780) in women with primary breast cancer. Cancer Res 1994;54:408-14
Howell A, DeFriend D, Robertson J, et al. Response to a specific antioestrogen (ICI 182780) in tamoxifen-resistant breast cancer. Lancet 1995;345:29-30
Robertson JF. Faslodex (ICI 182, 780), a novel estrogen receptor downregulator - future possibilities in breast cancer. J Steroid Biochem Mol Biol 2001;79:209-12
Auger S, Merand Y, Pelletier JD, et al. Synthesis and biological activities of thioether derivatives related to the antiestrogens tamoxifen and ICI 164384. J Steroid Biochem Mol Biol 1995;52:547-65
Hoffmann J, Bohlmann R, Heinrich N, et al. Characterization of new estrogen receptor destabilizing compounds: effects on estrogen-sensitive and tamoxifen-resistant breast cancer. J Natl Cancer Inst 2004;96:210-8
Claussner A, Nedelec L, Nique F, et al. 11 beta-amidoalkyl estradiols, a new series of pure antiestrogens. J Steroid Biochem Mol Biol 1992;41:609-14
Nique F, Van de Velde P, Bremaud J, et al. 11 beta-Amidoalkoxyphenyl estradiols, a new series of pure antiestrogens. J Steroid Biochem Mol Biol 1994;50:21-9
Van de Velde P, Nique F, Bouchoux F, et al. RU 58,668, a new pure antiestrogen inducing a regression of human mammary carcinoma implanted in nude mice. J Steroid Biochem Mol Biol 1994;48:187-96
Jin L, Borras M, Lacroix M, et al. Antiestrogenic activity of two 11 beta-estradiol derivatives on MCF-7 breast cancer cells. Steroids 1995;60:512-8
Dukes M, Chester R, Yarwood L, Wakeling AE. Effects of a non-steroidal pure antioestrogen, ZM 189,154, on oestrogen target organs of the rat including bones. J Endocrinol 1994;141:335-41
Von Angerer E, Biberger C, Leichtl S. Studies on heterocycle-based pure estrogen antagonists. Ann NY Acad Sci 1995;761:176-91
Walter G, Liebl R, Von Angerer E. Synthesis and biological evaluation of stilbene-based pure estrogen antagonists. Bioorg Med Chem Lett 2004;14:4659-63
Kanbe Y, Kim MH, Nishimoto M, et al. Discovery of thiochroman and chroman derivatives as pure antiestrogens and their structure-activity relationship. Bioorg Med Chem 2006;14:4803-19
Chen D, Pace PE, Coombes RC, Ali S. Phosphorylation of human estrogen receptor alpha by protein kinase A regulates dimerization. Mol Cell Biol 1999;19:1002-15
Pike AC, Brzozowski AM, Walton J, et al. Structural insights into the mode of action of a pure antiestrogen. Structure 2001;9:145-53
Dauvois S, White R, Parker MG. The antiestrogen ICI 182780 disrupts estrogen receptor nucleocytoplasmic shuttling. J Cell Sci 1993;106:1377-88
Devin-Leclerc J, Meng X, Delahaye F, et al. 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 (Baltimore) 1998;12:842-54
Long X, Nephew KP, Fulvestrant (ICI 182,780)-dependent interacting proteins mediate immobilization and degradation of estrogen receptor-alpha. J Biol Chem 2006;281:9607-15
Lupien M, Jeyakumar M, Hebert E, et al. Raloxifene and ICI182,780 increase estrogen receptor-alpha association with a nuclear compartment via overlapping sets of hydrophobic amino acids in activation function 2 helix 12. Mol Endocrinol (Baltimore) 2007;21:797-816
Jacquot Y, Laios I, Cleeren A, et al. Synthesis, structure, and estrogenic activity of 4-amino-3-(2-methylbenzyl)coumarins on human breast carcinoma cells. Bioorg Med Chem 2007;15:2269-82
Alarid ET. Lives and times of nuclear receptors. Mol Endocrinol (Baltimore) 2006;20:1972-81
Leclercq G, Lacroix M, Laios I, Laurent G. Estrogen receptor alpha: impact of ligands on intracellular shuttling and turnover rate in breast cancer cells. Curr Cancer Drug Target 2006;6:39-64
Wijayaratne AL, McDonnell DP. 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 2001;276:35684-92
Laios I, Journé F, Nonclercq D, et al. Role of the proteasome in the regulation of estrogen receptor alpha turnover and function in MCF-7 breast carcinoma cells. J Steroid Biochem Mol Biol 2005;94:347-59
Laios I, Journé F, Laurent G, et al. Mechanisms governing the accumulation of estrogen receptor alpha in MCF-7 breast cancer cells treated with hydroxytamoxifen and related antiestrogens. J Steroid Biochem Mol Biol 2003;87:207-21
Peekhaus NT, Chang T, Hayes EC, et al. Distinct effects of the antiestrogen Faslodex on the stability of estrogen receptors-alpha and -beta in the breast cancer cell line MCF-7. J Mol Endocrinol 2004;32:987-95
Howell A, Robertson JF, Quaresma Albano J, et al. 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 2002;20:3396-403
Osborne CK, Pippen J, Jones SE, et al. 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 2002;20:3386-95
Perey L, Paridaens R, Hawle H, et al. Clinical benefit of fulvestrant in postmenopausal women with advanced breast cancer and primary or acquired resistance to aromatase inhibitors: final results of phase II Swiss Group for Clinical Cancer Research Trial (SAKK 21/00). Ann Oncol 2007;18:64-9
Robertson JF, Osborne CK, Howell A, et al. Fulvestrant versus anastrozole for the treatment of advanced breast carcinoma in postmenopausal women: a prospective combined analysis of two multicenter trials. Cancer 2003;98:229-38
Dodwell D, Vergote I. A comparison of fulvestrant and the third-generation aromatase inhibitors in the second-line treatment of postmenopausal women with advanced breast cancer. Cancer Treat Rev 2005;31:274-82
Brodie AM, Schwarzel WC, Shaikh AA, Brodie HJ. The effect of an aromatase inhibitor, 4-hydroxy-4-androstene-3,17-dione, on estrogen-dependent processes in reproduction and breast cancer. Endocrinology 1977;100:1684-95
Mokbel K. The evolving role of aromatase inhibitors in breast cancer. Int J Clin Oncol 2002;7:279-83
Wiseman LR, Goa KL. Formestane. A review of its pharmacological properties and clinical efficacy in the treatment of postmenopausal breast cancer. Drugs Aging 1996;9:292-306
Perez Carrion R, Alberola Candel V, Calabresi F, et al. Comparison of the selective aromatase inhibitor formestane with tamoxifen as first-line hormonal therapy in postmenopausal women with advanced breast cancer. Ann Oncol 1994;5(Suppl 7):S19-24
Cuzick J. The ATAC trial: the vanguard trial for use of aromatase inhibitors in early breast cancer. Expert Rev Anticancer Ther 2007;7:1089-94
Forbes JF, Cuzick J, Buzdar A, et al. Effect of anastrozole and tamoxifen as adjuvant treatment for early-stage breast cancer: 100-month analysis of the ATAC trial. Lancet Oncol 2008;9:45-53
Ellis MJ, Ma C. Letrozole in the neoadjuvant setting: the P024 trial. Breast Cancer Res Treat 2007;105(Suppl 1):33-43
Hadjidakis DJ, Androulakis II. Bone remodeling. Ann NY Acad Sci 2006;1092:385-96
Khosla S. Minireview: the OPG/RANKL/RANK system. Endocrinology 2001;142:5050-5
Lindsay R. Hormones and bone health in postmenopausal women. Endocrine 2004;24:223-30
Hallworth RB. Prevention and treatment of postmenopausal osteoporosis. Pharm World Sci 1998;20:198-205
Greendale G, Caulsey J. Estrogens in osteoporosis. In: Cummings SR, Cosman F, Jamal SA, editors. Osteoporosis: an evidence-based guide to prevention and management. Philadelphia, PA: American College of Physicians, USA; 2002. p. 127-50
Rossouw JE, Anderson GL, Prentice RL, et al. Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results From the Women's Health Initiative randomized controlled trial. JAMA 2002;288:321-33
Albright F, Bloomberg E, Smith PH. Post-menopausal osteoporosis. Trans Assoc Am Phys 1940;4:298
Tobias JH, Compston JE. Does estrogen stimulate osteoblast function in postmenopausal women? Bone 1999;24:121-4
Lee K, Jessop H, Suswillo R, et al. Endocrinology: bone adaptation requires oestrogen receptor-alpha. Nature 2003;424:389
Shevde NK, Bendixen AC, Dienger KM, Pike JW. Estrogens suppress RANK ligand-induced osteoclast differentiation via a stromal cell independent mechanism involving c-Jun repression. Proc Natl Acad Sci USA 2000;97:7829-34
Bord S, Ireland DC, Beavan SR, Compston JE. The effects of estrogen on osteoprotegerin, RANKL, and estrogen receptor expression in human osteoblasts. Bone 2003;32:136-41
Raisz LG. Pathogenesis of osteoporosis: concepts, conflicts, and prospects. J Clin Invest 2005;115:3318-25
Samuels A, Perry MJ, Tobias JH. High-dose estrogen induces de novo medullary bone formation in female mice. J Bone Miner Res 1999;14:178-86
Riggs BL. The mechanisms of estrogen regulation of bone resorption. J Clin Invest 2000;106:1203-4
Oursler MJ. Estrogen regulation of gene expression in osteoblasts and osteoclasts. Crit Rev Eukaryot Gene Expr 1998;8:125-40
Michael H, Harkonen PL, Vaananen HK, Hentunen TA. Estrogen and testosterone use different cellular pathways to inhibit osteoclastogenesis and bone resorption. J Bone Miner Res 2005;20:2224-32
Love RR, Mazess RB, Barden HS, et al. Effects of tamoxifen on bone mineral density in postmenopausal women with breast cancer. N Engl J Med 1992;326:852-6
Jordan VC, Gapstur S, Morrow M. Selective estrogen receptor modulation and reduction in risk of breast cancer, osteoporosis, and coronary heart disease. J Natl Cancer Inst 2001;93:1449-57
Jordan VC, Phelps E, Lindgren JU. Effects of anti-estrogens on bone in castrated and intact female rats. Breast Cancer Res Treat 1987;10:31-5
Powles TJ, Hickish T, Kanis JA, et al. 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
Gottardis MM, Jordan VC. Antitumor actions of keoxifene and tamoxifen in the N-nitrosomethylurea-induced rat mammary carcinoma model. Cancer Res 1987;47:4020-4
Gottardis MM, Ricchio ME, Satyaswaroop PG, Jordan VC. Effect of steroidal and nonsteroidal antiestrogens on the growth of a tamoxifen-stimulated human endometrial carcinoma (EnCa101) in athymic mice. Cancer Res 1990;50:3189-92
Delmas PD, Bjarnason NH, Mitlak BH, et al. Effects of raloxifene on bone mineral density, serum cholesterol concentrations, and uterine endometrium in postmenopausal women. N Engl J Med 1997;337:1641-7
Delmas PD, Ensrud KE, Adachi JD, et al. Efficacy of raloxifene on vertebral fracture risk reduction in postmenopausal women with osteoporosis: four-year results from a randomized clinical trial. J Clin Endocrinol Metab 2002;87:3609-17
Siris ES, Harris ST, Eastell R, et al. Skeletal effects of raloxifene after 8 years: results from the continuing outcomes relevant to Evista (CORE) study. J Bone Miner Res 2005;20:1514-24
Martino S, Cauley JA, Barrett-Connor E, et al. Continuing outcomes relevant to Evista: breast cancer incidence in postmenopausal osteoporotic women in a randomized trial of taloxifene. J Natl Cancer Inst 2004;96:1751-61
Taranta A, Brama M, Teti A, et al. The selective estrogen receptor modulator raloxifene regulates osteoclast and osteoblast activity in vitro. Bone 2002;30:368-76
Qu Q, Harkonen PL, Vaananen HK. Comparative effects of estrogen and antiestrogens on differentiation of osteoblasts in mouse bone marrow culture. J Cell Biochem 1999;73:500-7
Tou L, Quibria N, Alexander JM. Regulation of human cbfa1 gene transcription in osteoblasts by selective estrogen receptor modulators (SERMs). Mol Cell Endocrinol 2001;183:71-9
Smith IE, Dowsett M. Aromatase inhibitors in breast cancer. N Engl J Med 2003;348:2431-42
Heshmati HM, Khosla S, Robins SP, et al. Role of low levels of endogenous estrogen in regulation of bone resorption in late postmenopausal women. J Bone Miner Res 2002;17:172-8
McCloskey E, Hannon R, Lakner C, et al. The letrozole (L), exemestane (E) and anastrozole (A) pharmacodynamics (LEAP) trial: a direct comparison of bone biochemical measurements between aromatase inhibitors (AIs) in healthy postmenopausal women. J Clin Oncol 2006;24:16S [abstract]
Body JJ, Bergmann P, Boonen S, et al. Management of cancer treatment-induced bone loss in early breast and prostate cancer - a consensus paper of the Belgian Bone Club. Osteoporos Int 2007;18:1439-50
Cummings SR, Black DM, Thompson DE, et al. Effect of alendronate on risk of fracture in women with low bone density but without vertebral fractures: results from the Fracture Intervention Trial. JAMA 1998;280:2077-82
Boonen S, Body JJ, Boutsen Y, et al. Evidence-based guidelines for the treatment of postmenopausal osteoporosis: a consensus document of the Belgian Bone Club. Osteoporos Int 2005;16:239-54
Brufsky A, Harker WG, Beck JT, et al. Zoledronic acid inhibits adjuvant letrozole-induced bone loss in postmenopausal women with early breast cancer. J Clin Oncol 2007;25:829-36
Gnant MF, Mlineritsch B, Luschin-Ebengreuth G, et al. Zoledronic acid prevents cancer treatment-induced bone loss in premenopausal women receiving adjuvant endocrine therapy for hormone-responsive breast cancer: a report from the Austrian Breast and Colorectal Cancer Study Group. J Clin Oncol 2007;25:820-8
Confavreux CB, Fontana A, Guastalla JP, et al. Estrogen-dependent increase in bone turnover and bone loss in postmenopausal women with breast cancer treated with anastrozole. Prevention with bisphosphonates. Bone 2007;41:346-52
Chlebowski RT. Bone health in women with early-stage breast cancer. Clin Breast Cancer 2005;5(Suppl 2):S35-40
Gallagher A, Chambers TJ, Tobias JH. The estrogen antagonist ICI 182,780 reduces cancellous bone volume in female rats. Endocrinology 1993;133:2787-91
Wakeling AE. Use of pure antioestrogens to elucidate the mode of action of oestrogens. Biochem Pharmacol 1995;49:1545-9
Rickard DJ, Waters KM, Ruesink TJ, et al. Estrogen receptor isoform-specific induction of progesterone receptors in human osteoblasts. J Bone Miner Res 2002;17:580-92
Sibonga JD, Dobnig H, Harden RM, Turner RT. Effect of the high-affinity estrogen receptor ligand ICI 182,780 on the rat tibia. Endocrinology 1998;139:3736-42
Turner RT, Evans GL, Dobnig H. The high-affinity estrogen receptor antagonist ICI 182,780 has no effect on bone growth in young male rats. Calcif Tissue Int 2000;66:461-4
Vandenput L, Swinnen JV, Van Herck E, et al. The estrogen receptor ligand ICI 182,780 does not impair the bone-sparing effects of testosterone in the young orchidectomized rat model. Calcif Tissue Int 2002;70:170-5
Lea CK, Flanagan AM. Ovarian androgens protect against bone loss in rats made oestrogen deficient by treatment with ICI 182,780. J Endocrinol 1999;160:111-7
Gunther DF, Calikoglu AS, Underwood LE. The effects of the estrogen receptor blocker, Faslodex (ICI 182,780), on estrogen-accelerated bone maturation in mice. Pediatr Res 1999;46:269-73
Gunther DF, Underwood LE, Calikoglu AS. Androgen-accelerated bone maturation in mice is not attenuated by Faslodex, an estrogen receptor blocker. Bone 2001;28:410-3
Donnez J, Hervais Vivancos B, Kudela M, et al. A randomized, placebo-controlled, dose-ranging trial comparing fulvestrant with goserelin in premenopausal patients with uterine fibroids awaiting hysterectomy. Fertil Steril 2003;79:1380-9
Robertson JF. Fulvestrant (Faslodex) how to make a good drug better. Oncologist 2007;12:774-84
Pearce ST, Jordan VC. The biological role of estrogen receptors alpha and beta in cancer. Crit Rev Oncol Hematol 2004;50:3-22
AstraZeneca website. Available from: www.astrazeneca.com
Femara website. Available from: www.femara.com/home.jsp?m=2
Aromasin website. Available from: www.aromasin.com
NCI clinical trial. Available from: www.cancer.gov/search/ ResultsClinicalTrialaAdvanced.aspx?protocolsearchid=4186256
Faslodex™ (fulvestrant) ongoing studies. Available from: www.astrazenecaclinicaltrials.com/article/514067.aspx
