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Background and development of aromatase inhibitors

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Aromatase Inhibitors

Part of the book series: Milestones in Drug Therapy MDT ((MDT))

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References

  1. Miller WR (1996) Aromatase inhibitors. Endocr Relat Cancer 3: 65–79

    CAS  Google Scholar 

  2. Henderson IC, Canellos GP (1980) Cancer of the breast: the past decade. New Engl J Med 302: 17–30: 78–90

    CAS  PubMed  Google Scholar 

  3. Miller WR (1990) Endocrine treatment for breast cancers: biological rationale and current progress. J Steroid Biochem Mol Biol 37: 467–480

    CAS  PubMed  Google Scholar 

  4. Miller WR (1989) Aromatase inhibitors in the treatment of advanced breast cancer. Cancer Treat Rev 16: 83–93

    Article  CAS  PubMed  Google Scholar 

  5. Combs DW (1995) Recent developments in aromatase inhibitors. Exp Opin Ther Patents 5: 529–534

    CAS  Google Scholar 

  6. Fishman J, Goto J (1981) Mechanisms of oestrogen biosynthesis: participation of multiple enzyme sites in placental aromatase hydroxylations. J Biol Chem 256: 4466–4471

    CAS  PubMed  Google Scholar 

  7. Means GD, Mahendroo MS, Corbin CJ, Mathis JM, Powell FE, Mendelson CR, Simpson ER (1989) Structural analysis of the gene encoding human aromatase cytochrome P-450, the enzyme responsible for estrogen biosynthesis. J Biol Chem 264: 19385–19391

    CAS  PubMed  Google Scholar 

  8. Bulun SE, Simpson ER (1994) Regulation of aromatase expression in human tissues. Breast Cancer Res Treat 30: 19–29

    Article  CAS  PubMed  Google Scholar 

  9. Johnston JO, Metcalf BW (1984) Aromatase: a target enzyme in breast cancer. In: Sunkara P (ed.): Novel approaches to cancer chemotherapy. Academic Press, London, 307–328

    Google Scholar 

  10. Kao YC, Cam LL, Laughton CA, Zhou D, Chen S (1996) Binding characteristics of seven inhibitors of human aromatase: a site directed mutagenesis study. Cancer Res 56: 3451–3461

    CAS  PubMed  Google Scholar 

  11. Santen RJ, Misbin RI (1981) Aminoglutethimide: review of pharmacology and clinical use. Pharmacotherapy 1: 95–120

    CAS  PubMed  Google Scholar 

  12. Vanden Bossche H., Moereels H, Koymans LMH (1994) Aromatic inhibitors-mechanisms for non-steroidal inhibitors. Breast Cancer Res Treat 30: 43–55

    CAS  PubMed  Google Scholar 

  13. Barone RM, Shamonki IM, Siiteri PK, Judd HL (1979) Inhibition of peripheral aromatization of androstenedionc to estrone in postmenopausal women with breast cancer using A’-testololactone. J Clin Endocrinol Metab 49: 672–676

    CAS  PubMed  Google Scholar 

  14. Griffiths CT, Hall TC, Saba Z, Barlow JJ, Nevinny HB (1973) Preliminary trial of aminoglutethimide in breast cancer. Cancer 32: 31–37

    CAS  PubMed  Google Scholar 

  15. Lipton A, Santen RJ (1974) Medical adrenalectomy using aminoglutethimide and dexamethasone in advanced breast cancer. Cancer 33: 503–512

    CAS  PubMed  Google Scholar 

  16. Segaloff A (1982) Testololactone: clinical trials. Cancer Res 42: 3387–3388

    Google Scholar 

  17. Segaloff A, Weeth JB, Meyer KK, Rongone EL, Cunningham ME (1962) Hormonal therapy in cancer of the breast. 19. Effect of oral administration of Δ1-testololactone on clinical course and hormonal excretion. Cancer 15: 633–635

    CAS  Google Scholar 

  18. Newsome HH, Brown PN, Terz JJ, Lawrence W (1977) Medical and surgical adrenalectomy in patients with advanced breast carcinoma. Cancer 39: 542–546

    CAS  PubMed  Google Scholar 

  19. Hughes SW, Burley DM (1970) Aminoglutethimide. a “side-effect” turned to therapeutic advantage. Postgrad Med J 46: 409–416

    CAS  Google Scholar 

  20. Thompson EA Jr, Siiteri PK (1974) Utilization of oxygen and reduced nicotinamide adenine dinucleotide phosphate by human placental microsomes during aromatization of androstenedione. J Biol Chem 249: 5364–5372

    CAS  PubMed  Google Scholar 

  21. Santen RJ, Santner S, Davis B, Veldhuis J, Samojlik E, Ruby E (1978) Aminoglutethimide inhibits extraglandular estrogen production in postmenopausal women with breast carcinoma. J Clin Endocr Metab 46: 1257–1265

    Google Scholar 

  22. Stuart-Harris R, Smith IE, Dowsett M, Bozek T, McKinna JA, Gazet J-C, Jeffcoate SL, Kurkure A, Carr L (1984) Low-dose aminoglutethimide in treatment of advanced breast cancer. Lancet 2: 604–607

    CAS  PubMed  Google Scholar 

  23. Graves PE, Salhanick HA (1979) Stereoselective inhibition of aromatase by enantiomers of aminoglutethimide. Endocrinology 105: 52–57

    CAS  PubMed  Google Scholar 

  24. Harris AL, Dowsett M, Cantwell BM, Sainsbury JR, Needham G, Farndon J, Wilson R (1986) Endocrine effects of low dose aminoglutethimide with hydrocortisone — an optimal hormone suppressive regime. Breast Cancer Res Treat 7: 68–72

    Google Scholar 

  25. Harris AL, Cantwell BM, Sainsbury JR, Needham G, Evans RG, Dawes PT, Wilson R, Farndon J (1986) Low dose aminoglutethimide (125 mg twice daily) with hydrocortisone for the treatment of advanced breast cancer. Breast Cancer Res Treat 7: 41–44

    Google Scholar 

  26. Murray R, Pitt P (1985) Low-dose aminoglutethimide without steroid replacement in the treatment of postmenopausal women with advanced breast cancer. Eur J Cancer Clin Oncol 21: 19–22

    CAS  PubMed  Google Scholar 

  27. Harris AL, Powles TJ, Smith IE, Coombes RC, Ford HT, Gazet JC, Harmer GE, Morgan M, White H, Parsons CA et al. (1983) Aminoglutethimide for the treatment of advanced postmenopausal breast cancer. Eur J Cancer Clin Oncol 19: 11–17

    CAS  PubMed  Google Scholar 

  28. Gale KE (1982) Treatment of advanced breast cancer with aminoglutethimide: a 14-year experience. Cancer Res 42(suppl.): 3389s–3396s

    CAS  PubMed  Google Scholar 

  29. Murray RM, Pitt P (1984) Treatment of advanced metastatic breast cancer, carcinoma of the prostate and endometrial cancer with aminoglutethimide. In: GA Nagel, RJ Santen (eds): Aminoglutethimide as an aromatase inhibitor in the treatment of cancer. Hans Huber, Bern, 109–122

    Google Scholar 

  30. Lipton A, Santen RJ, Harvey HA (1984) Aminoglutethimide clinical trials. In: HA Harvey, A Lipton, MA Michaels (eds): Breast cancer: therapeutic modalities current and future. MES Medical Education Services, Mississauga, 127–135

    Google Scholar 

  31. Santen RJ, Samojlik E, Worgul TJ (1981) Aminoglutethimide product profile. In: RJ Santen, IC Henderson (eds): Pharmanual: a comprehensive guide to the therapeutic use of aminoglutethimide. S Karger, Basel, 101–160

    Google Scholar 

  32. Santen RJ, Worgul TJ, Harvey H, Lipton A, Boucher A, Samojlik E, Wells S (1982) Aminoglutethimide as treatment of postmenopausal women with advanced breast carcinoma. Correlation of clinical and hormonal responses. Ann Intern Med 96: 94–101

    CAS  PubMed  Google Scholar 

  33. Harris AL (1985) Could aminoglutethimide replace adrenalectomy. Breast Cancer Res Treat 6: 201–211

    Article  CAS  PubMed  Google Scholar 

  34. Lawrence DV, Lipton A, Harvey HA, Santen RJ, Wells SA, Cox CE, White DS (1980) Influence of estrogen receptor status on response of metastatic breast cancer to aminoglutethimide. Cancer 45: 786–791

    CAS  PubMed  Google Scholar 

  35. Santen RJ, Worgul TJ, Samojlik E, Interroule A, Boucher AE, Lipton A, Harvey HA, White DS, Smart E, Cox C et al. (1981) A randomised trial comparing surgical adrenalectomy with aminoglutethimide plus hydrocortisone in women with advanced breast cancer. N Eng J Med 305: 545–551

    CAS  Google Scholar 

  36. Harris AL, Dowsett M, Jeffcoate SL, McKenna JA, Morgan M, Smith IE (1982) Endocrine and therapeutic effects of aminoglutethimide in premenopausal patients with breast cancer. J Clin Endocrinol Metab 55: 718–720

    CAS  PubMed  Google Scholar 

  37. Santen RJ (1984) Panel discussion. In: HA Harvey, A Lipton, MA Michaels (eds): Breast cancer: therapeutic modalities current and future. MES Medical Education Services, Mississauga

    Google Scholar 

  38. Murray RM, Pitt P (1981) Medical adrenalectomy in patients with advanced breast cancer resistant to anti-oestrogen treatment. Breast Cancer Res Treat 1: 91–95

    Article  CAS  PubMed  Google Scholar 

  39. Santen RJ, Wells SA (1980) The use of aminoglutethimide in the treatment of patients with metastatic carcinoma of the breast. Cancer 46: 1066–1074

    CAS  PubMed  Google Scholar 

  40. Smith IE, Harris AL, Morgan M, Ford HT, Gazet JC, Harmer CL, White H, Parsons CA, Villards A, Walsh G et al. (1981) Tamoxifen versus aminoglutethimide in the treatment of advanced breast carcinoma. A control randomised cross-over trial. Br Med J 283: 1432–1434

    CAS  Google Scholar 

  41. Smith IE, Harris AL, Morgan M, Gazet JC, McKenna JA (1982) Tamoxifen versus aminoglutethimide versus combined tamoxifen and aminoglutethimide in the treatment of advanced breast carcinoma. Cancer Res 42: 3430–3433

    Google Scholar 

  42. Smith IE, Stuart-Harris R, Harris AL, Dowsett M (1984) Aminoglutethimide alone and in combination in the treatment of advanced breast cancer: clinical and endocrine aspects. In: HA Harvey, A Lipton, MA Michaels (eds): Breast cancer: therapeutic modalities current and future. MES Medical Education Services, Mississauga, 145–149

    Google Scholar 

  43. Stuart-Harris RC, Smith IE (1984) Aminoglutethimide in the treatment of advanced breast cancer. Cancer Treat Rev 11: 189–204

    Article  CAS  PubMed  Google Scholar 

  44. Brodie AM, Schwarzel WC, Sheikh AA, Brodie HJ (1977) The effect of an aromatase inhibitor, 4-hydroxyandrostenedione, on estrogen-dependent processes in reproduction and breast cancer. Endocrinology 110: 1684–1695

    Google Scholar 

  45. Schwarzel WC, Kruggel W, Brodie HJ (1973) Studies on the mechanisms of estrogen biosynthesis. 8. The development of inhibitors of the enzyme system in human placenta. Endocrinology 92: 866–880

    CAS  PubMed  Google Scholar 

  46. Brodie AM, Garnett WM, Hendrickson JR, Tsai-Morris CH, Marcotte PA, Robinson CH (1981) Inactivation of aromatase in vitro by 4-hydroxy-4-androstene-3,17-dione and 4-acetoxy-4-androstene-3,17-dione and sustained effects in vivo. Steroids 38: 693–702

    Article  CAS  PubMed  Google Scholar 

  47. Cunningham D, Powles TJ, Dowsett M, Hutchison G, Brodie AM, Ford HT, Gazet JC, Coombes RC (1987) Oral 4-hydroxyandrostenedione, a new endocrine treatment for disseminated breast cancer. Cancer Chemother Pharmacol 20: 253–255

    Article  CAS  PubMed  Google Scholar 

  48. Dowsett M, Cunningham DC, Stein RC, Evans S, Dehennin L, Hedley A, Coombes RC (1989) Dose-related endocrine effects and pharmacokinetics of oral and intramuscular 4-hydroxyandrostenedione in postmenopausal breast cancer patients. Cancer Res 49: 1306–1312

    CAS  PubMed  Google Scholar 

  49. MacNeill FA, Jacobs S, Dowsett M, Lonning PE (1995) The effects of oral 4-hydroxyandrostenedione on peripheral aromatisation in post-menopausal breast cancer patients. Cancer Chemother Pharmacol 36: 249–254

    CAS  PubMed  Google Scholar 

  50. Coombes RC, Goss P, Dowsett M, Gazet JC, Brodie A (1984) 4-Hydroxy-androstenedionein treatment of postmenopausal patients with advanced breast cancer. Lancet 2: 1237–1239

    CAS  PubMed  Google Scholar 

  51. Dowsett M, Coombes RC (1994) Second generation aromatase inhibitor — 4-hydroxyandrostenedione. Breast Cancer Res Treat 30: 81–87

    Article  CAS  PubMed  Google Scholar 

  52. Dowsett M, Goss PE, Powles TJ, Hutchinson G, Brodie AMH, Jeffcoate SL, Coombes RC (1987) Use of the aromatase inhibitors 4-hydroxyandrostenedione in postmenopausal breast cancer: optimization of therapeutic dose and route. Cancer Res 47: 1957–1961

    CAS  PubMed  Google Scholar 

  53. Coombes RC, Hughes SWM, Dowsett M (1992) 4-Hydroxyandrostenedione: a new treatment for postmenopausal patients with breast cancer. Eur J Cancer 28: 1941–1945

    Google Scholar 

  54. Carrion RP, Candel VA, Calabresi F, Michel RT, Santos R, Delozier T, Goss P, Mauriac L, Feuilhade F, Freue M et al. (1994) Comparison of the selective aromatase inhibitor formestane with tamoxifen as first-line hormonal therapy in postmenopausal women with advanced breast cancer. Ann Oncol 5: S19–S24

    Google Scholar 

  55. Rose C, Freue M, Kjaer M, Boni C, Janicke F, Coombes C, Willemse PHB, van Belle S, Carrion RP, Jolivet J et al. (1996) An open, comparative randomized trial comparing formestane vs oral megestrol acetate as a second-line therapy in postmenopausal advanced breast cancer patients. Eur J Cancer 32A: 49

    Google Scholar 

  56. Bhatnagar AS, Hausler A (1987) Fortschritte in der Entwicklung neuer wirksamer und selektiver Aromatasehemmer. In: K Possinger, WR Miller (eds): Aromatasehemmer Neuer Perspektiven in der Behandlung des Mammakaranoms. Verlag: Munchen W Zuchshverat, Aktuelle Onkologie 38, 23–28

    Google Scholar 

  57. Schieweck K, Bhatnager AS, Matter A (1988) CGS 16949A, a new nonsteroidal aromatase inhibitor: effects on hormone-dependent and independent tumors in vitro. Cancer Res 48: 834–838

    CAS  PubMed  Google Scholar 

  58. Santen RJ, Demers LM, Adlercreutz H, Harvey H, Santner S, Sander S, Lipton A (1989) Inhibition of aromatase with CGS16949A in postmenopausal women. J Clin Endocrinol Metab 68: 99–106

    CAS  PubMed  Google Scholar 

  59. Coombes RC, Stein RC, Dowsett M (1989) Aromatase inhibitors in human breast cancer. In: JS Beck (ed.): Oestrogen and the human breast. Proceedings of the Royal Society of Edinburgh, 283–291

    Google Scholar 

  60. Santen RJ (1989) Novel methods of estrogen deprivation for treatment of breast disease. In: JS Beck (ed.): Oestrogen and the human breast. Proceedings of the Royal Society of Edinburgh.

    Google Scholar 

  61. Falkson G, Raats JI, Falkson HC (1992) Fadrozole hydrochloride, a new nontoxic aromatase inhibitor for the treatment of patients with metastatic breast cancer. J Steroid Biochem Mol Biol 43: 161–165

    Article  CAS  PubMed  Google Scholar 

  62. Hofken K (1993) Experience with aromatase inhibitors in the treatment of advanced breast cancer. Cancer Treat Rev 19: 37–44

    Google Scholar 

  63. Bonnefoi HR, Smith IE, Dowsett M, Trunet PF, Houston SJ, da Luz RJ, Rubens RD, Coombes RC, Powles TJ (1996) Therapeutic effects of the aromatase inhibitor fadrozole hydrochloride in advanced breast cancer. Br J Cancer 173: 539–542

    Google Scholar 

  64. Buzdar A, Jonat W, Howell A, Jones SE, Blomqvist C, Vogel CL, Eiermann W, Wolter JM, Azab M, Webster A et al. (1996) Anastrozole, a potent and selective aromatase inhibitor, versus megestrol acetate in postmenopausal women with advanced breast cancer: results of overview analysis of two phase III trials. J Clin Oncol 14: 2000–2011

    CAS  PubMed  Google Scholar 

  65. Thurlimann B, Beretta K, Bacchi M, Castiglione-Gertsch M, Goldhirsch A, Jungi WF, Cavalli F, Senn HJ, Fey M, Lohnert T (1996) First-line fadrozole HCI (CGS 16949A) versus tamoxifen in postmenopausal women with advanced breast cancer. Prospective randomised trial of the Swiss Group for Clinical Cancer Research SAKK 20/88. Ann Oncol 7: 471–479

    CAS  PubMed  Google Scholar 

  66. Lonning PE, Jacobs S, Jones A, Haynes B, Powles TJ, Dowsett M (1991) The influence of CGS 16949A on peripheral aromatisation in breast cancer patients. Br J Cancer 63: 789–793

    CAS  PubMed  Google Scholar 

  67. Demers LM, Melby JC, Wilson TE, Lipton A, Harvey GA, Santen RJ (1990) The effects of CGS 16949A, an aromatase inhibitor on adrenal mineralocorticoid biosynthesis. J Clin Endocrinol Metab 70: 1162–1166

    CAS  PubMed  Google Scholar 

  68. Stein RC, Dowsett M, Hedley A, Ford HT, Gazet JC, Coombes RC (1990) Preliminary study of the treatment of advanced breast cancer in postmenopausal women with aromatase inhibitor CGS 16949A. Cancer Res 50: 1381–1384

    CAS  PubMed  Google Scholar 

  69. Dowsett M, Smithers D, Moore J, Trunet PF, Coombes RC, Powles TJ, Rubens R, Smith IE (1994) Endocrine changes with the aromatase inhibitor fadrozole hydrochloride in breast cancer. Eur J Cancer 30A: 1453–1458

    CAS  PubMed  Google Scholar 

  70. Plourde PV, Dryoff M, Dukes M (1994) Arimidex (TM): a potent and selective fourth-generation aromatase inhibitor. Breast Cancer Res Treat 30: 103–111

    Article  CAS  PubMed  Google Scholar 

  71. Demers LM, Lipton A, Harvey HA, Kambic KB, Grossberg H, Brady C, Santen RJ (1993) The efficacy of CGS 20267 in suppressing estrogen biosynthesis in patients with advanced stage breast cancer. J Steroid Biochem 44: 687–691

    CAS  Google Scholar 

  72. Iveson TJ, Smith IE, Ahern J, Smithers DA, Trunet PF, Dowsett M (1993) Phase I study of the oral nonsteroidal aromatase inhibitor CGS 20267 in postmenopausal patients with advanced breast cancer. Cancer Res 53: 266–270

    CAS  PubMed  Google Scholar 

  73. van der Wall E, Donker TH, de Frankrijker E, Nortier HW, Thijssen JH, Blankenstein RA (1993) Inhibition of the in vivo conversion of androstenedione to estrone by the aromatase inhibitor vorozole in healthy postmenopausal women. Cancer Res 53: 4563–4566

    PubMed  Google Scholar 

  74. Wouters W, Snoeck E, De Coster R (1994) Vorozole, a specific non-steroidal aromatase inhibitor. Breast Cancer Res Treat 30: 89–94

    Article  CAS  PubMed  Google Scholar 

  75. Lonning PE (1996) Pharmacology of new aromatase inhibitors. The Breast 5: 202–208

    Google Scholar 

  76. Geisler J, King N, Dowsett M, Ottestad L, Lundgren S, Walton P, Kormeset PO, Lonning PE (1996) Influence of anastrozole (arimidex), a selective, nonsteroidal aromatase inhibitor, on in vivo aromatization and plasma estrogen levels in postmenopausal women with breast cancer. Br J Cancer 74: 1286–1291

    CAS  PubMed  Google Scholar 

  77. Dowsett M (1996) Biological background to aromatase inhibition. The Breast 5: 196–201

    Article  Google Scholar 

  78. Demers LM (1994) Effects of Fadrozole (CGS 16949A) and Letrozole (CGS 20267) on the inhibition of aromatase activity in breast cancer patients. Breast Cancer Res Treat 30: 95–102

    Article  CAS  PubMed  Google Scholar 

  79. Bhatnagar AS, Hausler A, Schieweck K, Lang M, Bowman R (1995) Highly selective inhibition of estrogen biosynthesis by CGS 20267, a new non-steroidal aromatase inhibitor. J Steroid Biochem Mol Biol 37: 1021–1027

    Google Scholar 

  80. Geisler J, Haynes B, Anker G, Dowsett M, Lonning PE (2002) Influence of letrozole and anastrozole on total body aromatization and plasma estrogen levels in postmenopausal breast cancer patients evaluated in a randomized, cross-over study. J Clin Oncol 20: 751–757

    Article  CAS  PubMed  Google Scholar 

  81. Gershanovich M, Chaudri HA, Campos D, Lurie H, Bonaventura A, Jeffrey M, Buzzi F, Bodrogi I, Ludwig H, Reichardt P et al. (1998) Letrozole, a new oral aromatase inhibitor: randomized trial comparing 2.5 mg daily, 0.5 mg daily and aminoglutethimide in postmenopausal women with advanced breast cancer. Ann Oncol 9: 639–645

    Article  CAS  PubMed  Google Scholar 

  82. Johannessen DC, Engan T, Di Salle E, Zurlo MG, Paolini J, Ornati G, Piscitelli G, Kvinnsland S, Lonning PE (1997) Endocrine and clinical effects of exemestane (PNU 155971), a novel steroidal aromatase inhibitor, in postmenopausal breast cancer patients: a phase I study. Clin Cancer Res 3: 1101–1108

    CAS  PubMed  Google Scholar 

  83. Vermeulen A, Paridaens R, Heuson JC (1983) Effects of aminoglutethimide on adrenal steroid secretion. Clin Endocrinol 19: 673–682

    CAS  Google Scholar 

  84. Miller WR, O’Neill JS (1989) The relevance of local estrogen metabolism within the breast. Proc Roy Soc Edin 95B: 203–217

    Google Scholar 

  85. Simpson ER, Mendelson CR (1989) The regulation of estrogen biosynthesis in human adipose tissue. In: Oestrogen and the human breast. Proc Roy Soc Edin 95: 153–159

    CAS  Google Scholar 

  86. Samojlik E, Santen RJ, Worgul TJ (1984) Suppression of residual oestrogen production with aminoglutethimide in women following surgical hypophyscctomy or adrenalectomy. Clin Endocrinol 20: 43–51

    CAS  Google Scholar 

  87. Adams JB, Garcia M, Rochefort H (1981) Estrogenic effects of physiological concentrations of 5-androstene 3B17B diol and its metabolism in MCF-7 human breast cancer cells. Cancer Res 41: 4720–4726

    CAS  PubMed  Google Scholar 

  88. Wander HK, Blosscy HCh and Nagcl GA (1986) Aminoglutethimide in the treatment of premenopausal patients with metastatic breast cancer. Eur J Cancer Clin Oncol 22: 1371–1374

    Article  CAS  PubMed  Google Scholar 

  89. Santen RJ, Samojlik E, Wells SA (1980) Resistance of the ovary to blockade of aromatization with aminoglutethimide. J Clin Endocrinol Metab 51: 473–477

    CAS  PubMed  Google Scholar 

  90. Stein RC, Dowsett M, Hedley A, Gazet JC, Ford HT, Coombes RC (1990) The clinical end endocrine effects of 4-hydroxyandrostenedione alone and in combination with goserelin in premenopausal women with advanced breast cancer. Br J Cancer 52: 679–683

    Google Scholar 

  91. Santen RJ, Manni A, Harvey H, Redmond C (1990) Endocrine treatment of breast cancer in women. Endocr Rev 11: 1–45

    Google Scholar 

  92. Sherman BM, Chapler FK, Crickard K, Wycoff D (1979) Endocrine consequences of continuous antiestrogen therapy with tamoxifen in premenopausal women. J Clin Invest 64: 398–404

    CAS  PubMed  Google Scholar 

  93. Groom GV, Griffiths K (1976) Effect of the anti-oestrogen tamoxifen on plasma levels of luteinizing hormone, follicle stimulating hormone, prolactin, oestradiol and progesterone in normal premenopausal women. J Endocrinol 70: 421–428

    CAS  PubMed  Google Scholar 

  94. Liehr JG (2002) Breast carcinogensis and its prevention by inhibition of estrogen genotoxicity. In: WR Miller, JN Ingle (eds): Endocrine therapy in breast cancer. Marcel Dekker, New York, 287–301

    Google Scholar 

  95. Sharpe RM (1994) Could environmental oestrogenic chemicals be responsible for some disorders of human male reproductive development. Curr Opin Urol 4: 295–301

    Google Scholar 

  96. Setchell KD, Borriello SP, Hulme P, Kirk DN, Axelson M (1984) Nonsteroidal estrogens of dietary origin: possible roles in hormone-dependent disease. Am J Clin Nutrition 40: 569–578

    CAS  Google Scholar 

  97. McLachlan JA, Newbold R (1987) Estrogens and development. Environ Health Perspect 75: 25–27

    CAS  PubMed  Google Scholar 

  98. Mouridsen H, Gershanovich M, Sun Y, Perez-Carrion R, Boni C, Monnier A, Apffelstaedt J, Smith R, Sleeboom HP, Janicke F et al. (2001) Superior efficacy of letrozole versus tamoxifen as first-line therapy for postmenopausal women with advanced breast cancer: results of a Phase III study of the International Letrozole Breast Cancer Group. J Clin Oncol 19: 2596–2606

    CAS  PubMed  Google Scholar 

  99. Mouridsen H, Sun Y, Gershanovich M, Perez-Carrion R, Smith R, Chaudri-Ross HA, Lang R, Brady C, Dugan M (2001) Final survival analysis of the double-blind, randomized, multinational Phase III trial of letrozole (Femara®) compared to tamoxifen as first-line hormonal therapy for advanced breast cancer. Breast Cancer Res Treat 69: 211

    Google Scholar 

  100. Nabholtz JM, Buzdar A, Pollak M, Harwin W, Burton G, Mangalik A, Steinberg M, Webster A, von Euler M (2000) Anastrozole is superior to tamoxifen as first-line therapy for advanced breast cancer in postmenopausal women: results of a North American multicenter randomized trial. Arimidex Study Group. J Clin Oncol 18: 3758–3767

    CAS  PubMed  Google Scholar 

  101. Dixon JM, Love CD, Bellamy CO, Cameron DA, Leonard RC, Smith H, Miller WR (2001) Letrozole as primary medical therapy for locally advanced and large operable breast cancer. Breast Cancer Res Treat 66: 191–199

    Article  CAS  PubMed  Google Scholar 

  102. Eiermann W, Paepke S, Appfelstaedt J (2001) Letrozole Neoadjuvant Breast Cancer Study Group. Preoperative treatment of postmenopausal breast cancer patients with letrozole. A randomized double-blind multicenter study. Ann Oncol 12: 1527–1532

    CAS  PubMed  Google Scholar 

  103. ATAC Trialist’s Group (2002) Anastrozole alone or in combination with tamoxifen versus tamoxifen alone for adjuvant treatment of postmenopausal women with early breast cancer: first results of the ATAC randomised trial. Lancet 359: 2131–2139

    Google Scholar 

  104. Miller WR, Sharpe RM (1998) Environmental oestrogens and human reproductive cancers. Endocr Relat Cancer 5: 69–96

    Article  CAS  Google Scholar 

  105. Miller WR, Dixon JM, Macfarlane L, Cameron D, Anderson TJ (2002) Pathological features of breast cancer response following neoadjuvant treatment with either letrozole or tamoxifen. Eur J Cancer 39: 462–468

    Google Scholar 

  106. Lipton A, Demers LM, Harvey HA, Kambic KB, Grossberg H, Brady C, Adlercruetz H, Trunet PF, Santen RJ (1995) Letrozole (CGS 20267). A Phase I study of a new potent oral aromatase inhibitor of breast cancer. Cancer 75: 2132–2138

    CAS  PubMed  Google Scholar 

  107. Johnston SR, Haynes BP, Sacks NP, McKinna JA, Griggs LJ, Jarman M, Baum M, Smith IE, Dowsett M (1993) Effect of oestrogen receptor status and time on the intra-tumoural accumulation of tamoxifen and N-desmethyltamoxifen following short-term therapy in human primary breast cancer. Breast Cancer Res Treat 28: 241–250

    Article  CAS  PubMed  Google Scholar 

  108. Miller WR, Anderson TJ, Iqbal S, Dixon JM (2002) Neoadjuvant therapy: prediction of response. In: WR Miller, JN Ingle (eds): Endocrine therapy in breast cancer. Marcel Dekker, New York, 223–229

    Google Scholar 

  109. Ellis MJ, Coop A, Singh B, Mauriac L, Llombert-Cussac A, Janicke F, Miller WR, Evans DB, Dugan M, Brady C (2001) Letrozole is more effective neoadjuvant endocrine therapy than tamoxifen for ErbB-1-and/or ErbB-2-positive, estrogen receptor-positive primary breast cancer: evidence from a phase III randomized trial. J Clin Oncol 19: 3808–3816

    CAS  PubMed  Google Scholar 

  110. Dixon JM, Jackson J, Hills M, Renshaw L, Cameron DA, Anderson TJ, Miller WR, Dowsett M (2004) Anastrozole demonstrates clinical and biological effectiveness in oestrogen receptor-positive breast cancers, irrespective of the erbB2 status. Eur J Cancer 40: 2742–2747

    Article  CAS  PubMed  Google Scholar 

  111. Allegra JC, Barlock A, Huff KK, Lippman ME (1980) Changes in multiple or sequential estrogen receptors in breast cancer. Cancer 45: 792–794

    CAS  PubMed  Google Scholar 

  112. Hawkins RA, Tesdale AL, Anderson ED, Levack PA, Chetty U, Forrest AP (1990) Does the oestrogen receptor concentration of a breast cancer change during systemic therapy? Br J Cancer 61: 877–880

    CAS  PubMed  Google Scholar 

  113. Miller WR, Hawkins RA, Mullen P, Sourdaine P, Telford J (1995) Aromatase inhibition: determinants of response and resistance. Endocr Relat Cancer 2: 73–85

    CAS  Google Scholar 

  114. Fuqua SA, Wiltschke C, Castles C, Wolf D, Allred DC (1995) A role for estrogen-receptor variants in endocrine resistance. Endocr Relat Cancer 2: 19–25

    CAS  Google Scholar 

  115. Fujimoto N, Katzenellenbogen BS (1994) Alteration in the agonist/antagonist balance of antiestrogens by activation of protein kinase A signalling pathways in breast cancer cells: antiestrogen-selectivity and promoter-dependence. Mol Endocrinol 8: 296–304

    Article  CAS  PubMed  Google Scholar 

  116. Isaacs JT (1988) Clonal heterogeneity in relation to response. In: BA Stoll (ed.): Endocrine management of cancer: biological bases. Karger, Basel, 125–140

    Google Scholar 

  117. Howell A, Defriend D, Anderson E (1995) Clues to the mechanism of endocrine resistance from clinical studies in advanced breast cancer. Endocr Relat Cancer 2: 131–139

    CAS  Google Scholar 

  118. Santen RJ (1982) Overall experience with aminoglutethimide in the management of advanced breast cancer. In: RW Elsdon-Dew, IM Jackson, GFB Birdwood (eds): Aminoglutethimide: an alternative endocrine therapy for breast carcinoma. Academic Press, London, 3–7

    Google Scholar 

  119. Herman ME, Katzenellenbogen B (1994) Alterations in transforming growth factor-α and-β production and cell responsiveness during the progression of MCF-7 human breast cancer cells to estrogen-autonomous growth. Cancer Res 54: 5867–5874

    CAS  PubMed  Google Scholar 

  120. King RJ, Wang DY, Daly RJ, Darbre PD (1989) Approaches to studying the role of growth factors in the progression of breast tumours from the steroid sensitive to insensitive state. J Steroid Biochem 34: 133–138

    Article  CAS  PubMed  Google Scholar 

  121. Miller WR, O’Neill JS (1988) The importance of local synthesis of estrogen within the breast. Steroids 50: 537–548

    Google Scholar 

  122. Kadohama N, Yarborough C, Zhou D, Chen S, Osawa Y (1992) Kinetic properties of aromatase mutants ProSOSPhe, Asp309Asn and Asp309Ala and their interactions with aromatase inhibitors. J Steroid Biochem Mol Biol 43: 693–701

    Article  CAS  PubMed  Google Scholar 

  123. James VH, Reed MJ, Adams EF, Ghilchick M, Lai LC, Coldham NG, Newton CJ, Purohit A, Owen AM, Singh A et al. (1989) Oestrogen uptake and metabolism in vivo. Proc Roy Soc Edin 95B: 185–193

    Google Scholar 

  124. Miller WR (1992) In vitro and in vivo effects of 4-hydroxyandrostenedione on steroid and tumour metabolism. In: RC Coombes, M Dowsett (eds): 4-Hydroxy-androstenedione — a new approach to hormone-dependent cancer, International Congress and Symposium Series. Royal Society of Medicine Services, London, 45–50

    Google Scholar 

  125. Sourdaine P, Parker MG, Telford J, Miller WR (1994) Analysis of the aromatase cytochrome P450 gene in human breast cancer. J Mol Endocrinol 13: 331–337

    CAS  PubMed  Google Scholar 

  126. Lonning PE, Bajetta E, Murray R, Tubiana-Hulin M, Eisenberg PD, Mickiewicz E, Celio L, Pitt P, Mita M, Aaronson NK et al. (2000) Activity of exemestane (Aromasin) in metastatic breast cancer after failure of nonsteroid aromatase inhibitors: a phase II trial. J Clin Oncol 18: 2234–2244

    CAS  PubMed  Google Scholar 

  127. Carlini P, Frassoldati A, De Marco S, Casali A, Ruggeri EM, Nardi M, Papaldo P, Fabi A, Paoloni F, Cognetti F (2001) Formestane, a steroidal aromatase inhibitor after failure of non-steroidal aromatase inhibitors (anastrozole and letrozole): is a clinical benefit still available? Ann Oncol 12: 1539–1543

    Article  CAS  PubMed  Google Scholar 

  128. Miller WR, Jackson J (2003) The therapeutic potential of aromatase inhibitors. Expert Opin Invest Drugs 12: 337–351

    CAS  Google Scholar 

  129. Goss PE (2001) Chemoprevention with aromatase inhibitors. In: WR Miller, RJ Santen (eds): Aromatase inhibition and breast cancer. Marcel Dekker, New York, 161–181

    Google Scholar 

  130. Kaplowitz PB (2001) Aromatase inhibitors as therapy for pubertal gynecomastia. In: WR Miller, RJ Santen (eds): Aromatase inhibition and breast cancer. Marcel Dekker, New York, 259–266

    Google Scholar 

  131. Smith MR (2001) Aromatase inhibition and prostate cancer. In: WR Miller, RJ Santen (eds): Aromatase inhibition and breast cancer. Marcel Dekker, New York, 271–276

    Google Scholar 

  132. Bulun S, Zeitoun KM, Takayama K, Sasano H, Simpson ER (2001) Aromatase in endometriosis: biological and clinical application. In: WR Miller, RJ Santen (eds): Aromatase inhibition and breast cancer. Marcel Dekker, New York, 279–291

    Google Scholar 

  133. Geisler J, King N, Anker G, Ornati G, Di Salle E, Lønning PE, Dowsett M (1998) In vivo inhibition of aromatization by exemestane, a novel irreversible aromatase inhibitor, in postmenopausal breast cancer patients. Clin Cancer Res 4(9): 2089–2093

    CAS  PubMed  Google Scholar 

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  1. Breast Unit, Paderewski Building, Western General Hospital, Edinburgh, EH4 2XU, UK

    William R. Miller

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  1. AstraZeneca, Global Discovery, Mereside, Alderley Park, Macclesfield, Cheshire, SK10 4TG, UK

    Barrington J.A. Furr

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Miller, W.R. (2006). Background and development of aromatase inhibitors. In: Furr, B.J. (eds) Aromatase Inhibitors. Milestones in Drug Therapy MDT. Birkhäuser Basel. https://doi.org/10.1007/3-7643-7418-7_1

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