Skip to main content
SpringerLink
Log in

Clinical Utility of Aromatase Inhibitors

  • Chapter
Hormone Therapy in Breast and Prostate Cancer

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

  • 329 Accesses

Abstract

Over the last 30 years, aromatase inhibitors have progressed from the status of experimental agents to that of established second-line treatment of advanced breast cancer, and their use in the adjuvant setting is currently being tested in large multicenter trials. The contrast between the chance discovery of the prototype inhibitor, aminoglutethimide, and the intensive development of the new third-generation compounds could not be more striking. Aminoglutethimide was developed in the 1950s as a derivative of the anticonvulsant glutethimide (1); having been found to have a superior therapeutic index to its parent compound, it was marketed in the USA for the treatment of epilepsy in1960. How-ever, between 1963 and 1965, several cases of severe endocrine disturbance in children treated with the drug were reported, leading the Food and Drug Administration (FDA) to withdraw its licence in 1966.

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

Access this chapter

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

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Hughes S, Burley D. ASantnarminoglutethimide: a ‘side-effect’ turned to therapeutic advantage. Postgrad Med J 1970; 46:409–416.

    Article  CAS  Google Scholar 

  2. Hall T, Barlow J. Treatment of metastatic breast cancer with aminoglutethimide. Clin Res 1969; 17:402.

    Google Scholar 

  3. Lipton A, Santen R. Medical adrenalectomy using aminoglutethimide and dexamethasone in advanced breast cancer. Cancer 1974; 33:503–512.

    Article  PubMed  CAS  Google Scholar 

  4. Santen R, Santner S, Davis, B, Veldhuis, J, Samojlik, E, Ruby, E. Aminoglutethimide inhibits extraglandular estrogen production in postmenopausal women with breast carcinoma. J Clin Endocrinol Metab 1978; 47:1257–1265.

    Article  PubMed  CAS  Google Scholar 

  5. Miller WR, Forrest AP. Oestradiol synthesis from C19 steroids by human breast cancer. Br J Cancer 1974; 33:16–18.

    Google Scholar 

  6. Silva M, Rowlands M, Dowsett M, Gasterson B, McKinna JA Fryatt I, et al. Intratumoral aromatase as a prognostic factor in human breast carcinoma. Cancer Res 1989; 49:2588–2591.

    PubMed  CAS  Google Scholar 

  7. Lipton A, Santer RJ, Santner S, Harvey HA, Sanders SI, Matthews YL. Prognostic value of breast cancer aromatase. Cancer 1992; 70:1951–1955.

    Article  PubMed  CAS  Google Scholar 

  8. Thorsen T, Tangen N, Stoa KF. Concentrations of endogenous estradiol as related to estradiol receptor sites in breast tumour cytosol. Eur J Cancer Clin Oncol 1982; 18:333–337.

    Article  PubMed  CAS  Google Scholar 

  9. van Landeghem AA, Poortman J, Nabuun M, Thijssen JH. Endogenous concentration and subcellular distribution of estrogens in normal and malignant breast tissue. Cancer Res 1985; 45:2900–2906.

    PubMed  Google Scholar 

  10. James V, Reed M. Steroid hormones and human cancer. Prog Cancer Res Ther 1980; 14:471–487.

    CAS  Google Scholar 

  11. Early Breast Cancer Trialists’ Collaborative Group (EBCTCG). Systemic treatment of early breast cancer by hormonal, cytotoxic and immune therapy. Lancet 1992; 339:1–15, 71–85.

    Google Scholar 

  12. Jaiyesimi I, Buzdar A, Decker DA, Hortobaggi GN. Use of tamoxifen for breast cancer: twenty-eight years later. J Clin Oncol 1995; 13:513–529.

    PubMed  CAS  Google Scholar 

  13. Gale K, Anderson J, Tonneg DC, Mansow EG, Davis TE, Horton J, et al. An Eastern Cooperative Oncology Group Phase III trial comparing aminoglutethimide to tamoxifen. Cancer 1994; 73:354–361.

    Article  PubMed  CAS  Google Scholar 

  14. Garcia-Giralt E, Ayme Y, Carton M, Daban A, Delozier T, Fargeot P, et al. Second and third line hormonotherapy in advanced post-menopausal breast cancer: a multicenter randomized trial comparing medroxyprogesterone acetate with aminoglutethimide in patients who have become resistant to tamoxifen. Breast Cancer Res Treatment 1993; 24:139–145.

    Article  Google Scholar 

  15. MacNeill F, Jones A, Jacobs S, Lonning PE, Powles TJ, Dowsett M. The influence of Aminoglutethimide and its analogue Rogletimide on peripheral aromatisation in breast cancer. Br J Cancer 1992; 66:692–697.

    PubMed  CAS  Google Scholar 

  16. Miller W. Aromatase inhibitors. Endoc-Rel Cancer 1996; 3:65–79.

    Article  CAS  Google Scholar 

  17. Howell A, Mackintosh J, Jones M, Redford J, Wagstaff J, Sellwood RA. The definition of the “no change” category in patients treated with endocrine therapy and chemotherapy for advanced carcinoma of the breast. Eur J Cancer Clin Oncol 1988; 24:1567–1572.

    Article  PubMed  CAS  Google Scholar 

  18. Santen R, Worgul T, Samojlik E, Interrante A, Boucher AE, Lipton A, et al. A randomised trial comparing surgical adrenalectomy with aminoglutethimide plus hydrocortione in women with advanced breast cancer. N Engl J Med 1981; 305:545–551.

    Article  PubMed  CAS  Google Scholar 

  19. Lipton A, Harvey HA, Santer RJ, Boucher A, White D, Bernatt A. A randomised trial of aminoglutethimide versus tamoxifen in metastatic breast cancer. Cancer 1982; 50:2265–2268.

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  21. Harris AL, Dowsett M, Smith JE, Powles TJ. Suppression of plasma 6-keto-prostaglandin F1-alfa and 13, 14-dihydro-15-ketoprostaglandin F2-alfa by aminoglutethimide in advanced breast cancer. Br J Cancer 1983; 48:595–598.

    PubMed  CAS  Google Scholar 

  22. Harris A. Aminoglutethimide: a new endocrine therapy in breast cancer. Exp Cell Biol 1985; 53:1–8.

    PubMed  CAS  Google Scholar 

  23. Smith I, Harris A, Morgan M, Ford HT, Gazet JC, Harmer CL, et al. Tamoxifen versus aminoglutethimide in the treatment of advanced breast cancer. A controlled randomised cross-over trial. BMJ 1981; 283:1432–1434.

    Article  PubMed  CAS  Google Scholar 

  24. Smith I, Harris A, Morgan M, Gazet JC, McKinna JA. Tamoxifen versus aminoglutethimide versus combined tamoxifen and amiaoglutethimide in the treatment of advanced breast cancer. Cancer Res 1982; 42:3430S–3433S.

    PubMed  CAS  Google Scholar 

  25. Milsted R, Habeshaw T, Kaye S, Sangster G, Macbeth F, Cambell-Ferguson J, et al. A randomized trial of tamoxifen versus tamoxifen with aminoglutethimide in postmenopausal women with advanced breast cancer. Cancer Chemother Pharmacol 1985; 14:272–273.

    Article  PubMed  CAS  Google Scholar 

  26. Ingle J, Green S, Ahmann DL, Long HJ, Edmonson JH, Rubin J, et al. Randomized trial of tamoxifen alone or combined with aminoglutethimide and hydrocortisone in women with metastatic breast cancer. J Clin Oncol 1986; 4:958–964.

    PubMed  CAS  Google Scholar 

  27. Alonso-Munoz N, Ojeda-Gonzalez M. Randomized trial of tamoxifen versus aminoglutethimide and versus tamoxifen and aminoglutethimide in advanced postmenopausal breast cancer. Oncology 1988; 45:350–353.

    Article  PubMed  CAS  Google Scholar 

  28. Lien E, Anker G, Lonning PE, Solheim E, Ueland PM. Decreased serum concentrations of tamoxifen and its metabolites induced by aminoglutethimide. Cancer Res 1990; 50:5851–5857.

    PubMed  CAS  Google Scholar 

  29. Dowsett M, PC, Johnston SRD, Hoston SJ. Miles DW, Verbeek JA, Smith IE. Pharmacokinetic interaction between letrozole and tamoxifen in postmenopausal patients with advanced breast cancer. Breast 1997; 6:245.

    Google Scholar 

  30. Lonning P. Aromatase inhibition: past, present and future, in Endocrine Aspects of Breast Cancer. Dowsett M, Parthenon Publishing, Carnforth, UK, 1992, pp 53–76.

    Google Scholar 

  31. Dowsett M, Cunningham DC, Stein RC, Evans S, Dehernin L, et al. Dose-related endocrine effects and pharnacokinetics of oral and intramuscular 4-hydroxyandrostenedione in postmenopausal breast cancer patients. Cancer Res 1989; 49:1306–1312.

    PubMed  CAS  Google Scholar 

  32. Dowsett M, Goss PE, Powles TJ, Hutchison G, Brodie AMH, Jefferate SL, et al. Use of the aromatase inhibitor 4-hydroxyandrostenedione in postmenopausal breast cancer: optimisation of therapeutic dose and route. Cancer Res 1987; 47:1957–61.

    PubMed  CAS  Google Scholar 

  33. Coombes RC, Goss PE, Dowsett M, Hutchinson G, Cunningham D, Jarman M, Brodie AM. 4-Hydroxyandrostenedione treatment for postmenopausal patients with advanced breast cancer. Steroids 1987; 50:245–252.

    Article  PubMed  CAS  Google Scholar 

  34. Stein RC, Dowsett M, Coombes RC. Studies of formestane alone and in combination with goserelin in premenopausal breast cancer. Adv Clin Oncol 1994; 2:149–154.

    Google Scholar 

  35. Jones AL, MacNeill F, Jacobs S, Lonning PE, Dowsett M, Powles TJ. The influence of intramuscular 4-hydroxyandrostenedione on peripheral aromatisation in breast cancer patients. Eur J Cancer 1992; 28A:1712–1716.

    Article  PubMed  CAS  Google Scholar 

  36. Coombes RC, Stein RC, Dowsett M. Aromatase inhibitors in human breast cancer. Proc R Society Edinburgh 1989; 95B:283–291.

    Google Scholar 

  37. Hoffken K, Jonat W, Possinger K, Kolbel M, Kunz T, Wagner H, Becher R, et al. Aromatase inhibition with 4-hydroxyandrostenedione in the treatment of postmenopausal patients with advanced breast cancer a phase II study. J Clin Oncol 1990; 8:875–880.

    PubMed  CAS  Google Scholar 

  38. Pickles T, Perry L, Murray P, Plowman P. 4-hydroxyandrostenedione: further clinical and extended endocrine observations. Br J Cancer 1990; 62:309–313.

    PubMed  CAS  Google Scholar 

  39. Santen RJ, Manni A, Harvey H, Redmond C. Endocrine treatment of breast cancer in women. Endoc Rev 1990; 11:1–45.

    Article  Google Scholar 

  40. Goss PE, Garyn KM. Current perspectives of aromatase inhibitors in breast cancer. J Clin Oncol 1994; 12:2460–2470.

    PubMed  CAS  Google Scholar 

  41. Perez-Carrion R, Alberola C, Calabresi F, Michel RT, Santos R, Delozier T, 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; 9:S19–S24.

    Google Scholar 

  42. Geisler J, King N, Anker G, Ornati G, Di Salle E, Lonning PE, et al. In vivo inhibition of whole body aromatisation by exemestane (PNU 155971), a novel steroidal aromatase inhibitor, in postmenopausal breast cancer patients. Breast Cancer Res Treatment 1997; 46(1):55.

    Google Scholar 

  43. Lonning PE, Paridaens R, Thurlimann B, Piscitelli G, di Salle E. Exemestane experience in breast cancer. J Steroid Biochem Mol Biol 1997; 61:151–155.

    Article  PubMed  CAS  Google Scholar 

  44. Lonning PE, Jacobs S, Jones A, Haynes B, Powles T, Dowsett M. The influence of CGS 16949A on peripheral aromatisation in breast cancer patients. Br J Cancer 1991; 63(5):789–793.

    PubMed  CAS  Google Scholar 

  45. Demers LM, LA, Harvey HA, Hanagan J, Mulagha M, Santen RI. The effects of long term fadrozole hydrochloride treatment in patients with advanced stage breast cancer. J Steroid Biochem Mol Biol 1993; 44:683–685.

    Google Scholar 

  46. Hoffken K. Experience with aromatase inhibitors in the treatment of advanced breast cancer. Cancer Treatment Rev 1993; 19(Suppl B):37–44.

    Article  Google Scholar 

  47. Bonnefoi WR, Johnston S, Dowsett M, Trunet PF, Houston SJ, da Luz RJ, Rubens RD, et al. Therapeutic effects of the aromatase inhibitor fadrozole hydrochloride in advanced breast cancer. Br J Cancer 1996; 73:539–542.

    PubMed  CAS  Google Scholar 

  48. Miller AA, Lipton A, Henderson CC, Navari R, Mulagha MT, Cooper J. Fadrozole hydrochloride in postmenopausal patients with advanced breast carcinoma. Cancer 1996; 78:789–793.

    Article  PubMed  CAS  Google Scholar 

  49. Falkson CI, Falkson HC. A randomised study of CGS 16949A (fadrozole) versus tamoxifen in previously untreated patients with metastatic breast cancer. Ann Oncol 1996; 7:465–469.

    PubMed  CAS  Google Scholar 

  50. Buzdar AU, Smith R, Vogel C, Bonomi P, Kelter AM, Favis G, et al. Fadrozole HCI (CGS- 16949A) versus megestrol acetate treatment of postmenopausal patients with metastatic breast cancer: results of two randomised double blind controlled multiinstitutional trials. Cancer 1996a; 77:2503–2513.

    Article  PubMed  CAS  Google Scholar 

  51. Thurlimann B, Beretta K, Bacchi M, Castiglione-Certsch M, Goldhirsch A, Jungi WF, et al. First-line fadrozole HCl (CGS 16949A) versus tamoxifen in postmenopausal women with advanced breast cancer. Prospective randomised trial of the Swiss group for Clinical Cancer Research SAKK. Ann Oncol 1996; 7:471–479.

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  53. Stein RC, Dowsett M, Davenport J, Hedley A, Ford HT, Gazet JC, et al. Preliminary study of the treatment of advanced breast cancer in postmenopausal women with the aromatase inhibitor CGS 16949A. Cancer Res 1990; 50:1381–1384.

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  55. Johnston SRD, Smith IE, Doody D, Jacobs S, Robertshaw H, Dowsett M. Clinical and endocrine effects of the oral aromatase inhibitor vorozole in postmenopausal patients with advanced breast cancer. Cancer Res 1994; 54:5875–5881.

    PubMed  CAS  Google Scholar 

  56. Juranka PF, Zastaway RL, Ling V. P-glycoprotein multidrug resistance and a super family of membrane-associated transport proteins. FASEB J 1989; 3:2583–2592.

    PubMed  CAS  Google Scholar 

  57. Yates RA, Dowsett M, Fisher GV, Selen A, Wyld PJ. Arimidex (ZD1033): a selective, potent inhibitor of aromatase in post-menopausal female volunteers. Br J Cancer 1996; 73:543–548.

    PubMed  CAS  Google Scholar 

  58. Geisler J, King N, Dowsett M, Ottestad L, Lundgren S, Walton P, et al. Influence of Anastozole (Arimidex) a non-steroidal aromatase inhibitor, on in vivo aromatisation and plasma oestrogen levels in postmenopausal women with breast cancer. Br J Cancer 1996; 74:1289–1291.

    Google Scholar 

  59. Dowsett M, Jones A, Johnston SRD, Jacobs S, Trunet P, Smith IE. In vivo measurement of aromatase inhibition by letrozole (CGS 20267) in postmenopausal patients with breast cancer. Clin Cancer Res 1995; 1:1511–1515.

    PubMed  CAS  Google Scholar 

  60. Buzdar A, Jonat W, Howell A, Jones SE, Blomqvist C, Vogel CL, Eiermann W, et al. 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 1996b; 14:2000–2011.

    PubMed  CAS  Google Scholar 

  61. Dombernowsky P, Smith I, Falkson G, Leonard R, Panasci L, Bellmunt J, et al. Letrozole, a new oral aromatase inhibitor for advanced breast cancer: double-blind randomized trial showing a dose effect and improved efficacy and tolerability compared with megestrol acetate. J Clin Oncol 1998; 16:453–461.

    PubMed  CAS  Google Scholar 

  62. Smith I, Dombernowsky P, Falkson G, Leonard R, Panasci L, Bellmunt J, et al. Double-blind trial in postmenapausal (PMP) women with advanced breast cancer (ABC) showing a doseeffect and superiority of 2.5 mg letrozole over megestrol acetate. Eur J Cancer 1996; 32A:49.

    Article  Google Scholar 

  63. Bergh J, Bonneterre J, Illiger HJ, Murray R, Nortier J, Paridaens R, et al. Vorozole (Rivizor ™) versus aminoglutethimide (AG) in the treatment of postmenopausal breast cancer relapsing after tamoxifen. Proc Am Society Clin Oncol 1997; 16:155a.

    Google Scholar 

  64. Marty M, Geschanovich M, Campos B, Romieu G, Lurie H, Bonaventura T, et al. Letrozole, a new potent selective aromatase inhibitor (AI) superior to aminoglutethimide (AG) in postmenopausal women with advanced breast cancer (ABC) previously treated with antiestrogens. Proc Am Society Clin Oncol 1997; 16:156a.

    Google Scholar 

  65. Buzdar A, Jonat W, Howell A, Yin H, Lee D. Significant improved survival with Arimidex (anastrozole) versus megestrol acetate in postmenopausal advanced breast cancer: updated results of two randomised trials. Proc Am Society Clin Oncol 1997; 16:156a.

    Google Scholar 

  66. Buzdar AU, Jonat W, Howell A, Jones SE, Blomqvist CP, Vogel CL, et al. Anastrozole versus megestrol acetate in postmenopausal women with advanced breast cancer: Results of a survival update based on a combined analysis of data from two mature phase III trials. Cancer (in press).

    Google Scholar 

  67. Rose C, Kamby C, Mouridsen HT, Bastholt L, Brinker M, Skovgaard-Poulsen H, Andersen AP, et al. Combined endocrine treatment of postmenopausal patients with advanced breast cancer. A randomized trial of tamoxifen versus tamoxifen plus aminoglutethimide and hydrocortisone. Breast Cancer Res Treatment 1986; 7(Suppl):S45–S50.

    Article  Google Scholar 

  68. Dowsett M, Tobias JS, Howell A, Blackman A, Welch H, King N, et al. The effect of anestrogale on the pharnacokinetics of tamoxifen in postmenopausal women with early breast cancer. Brit J Cancer

    Google Scholar 

  69. Masamura S, Santner SJ, Heitjan DF, Santen RJ. Estrogen deprivation causes estradiol hypersensitivity in human breast cancer cells. J Clin Endocrinol Metab 1995; 80:2918–2925.

    Article  PubMed  CAS  Google Scholar 

  70. Adams J. Hermaphrodiol: A ‘new’ estrogen and its role in the etiology of human breast cancer. Commentaries on research in breast disease, vol. 3 (Bulbrook R, Taylor DJ, eds). Alan R. Liss, New York, 1983, pp 133.

    Google Scholar 

  71. Rubens RD, Tirson CL, Coleman RE, Knight RK, Tong D, Winter PJ, et al. Prednisolone improves the response to primary endocrine treatment for advanced breast cancer. Br J Cancer 1988; 58:626–630.

    PubMed  CAS  Google Scholar 

  72. Bates T, Riley DL, Houghton S, Baum M. Breast cancer in elderly women: a Cancer Research Campaign trial comparing treatment with tamoxifen and optimal surgery with tamoxifen alone. Br J Surg 1991; 78:591–594.

    Article  PubMed  CAS  Google Scholar 

  73. Mustacchi G, Milani S, Pluchinotta A, De Matteus A, Bubagotti A, Berrota A. Tamoxifen or surgery plus tamoxifen as primary treatment for elderly patients with operable breast cancer. AntiCancer Res 1994; 14:2197–2200.

    PubMed  CAS  Google Scholar 

  74. Fisher B, Gunduz N, Coyle J, Rodock C, Saffer E. Presence of a growth-stimulating factor in serum following tumor removal in mice. Cancer Res 1989; 49:1996–2001.

    PubMed  CAS  Google Scholar 

  75. Anderson EDC, Anderson E, Hawkins RA, Anderson TJ, Leonard RCF, Chetty U. Primary systemic therapy for operable breast cancer. Br J Cancer 1991; 63:561–566.

    PubMed  CAS  Google Scholar 

  76. Gazet J-C, Coombes RC, Ford HT, Griffin M, Corbishley C, Nakinde V, Lowndes S, et al. Assessment of the effect of pretreatment with neoadjuvant therapy on primary breast cancer. Br J Cancer 1996; 73:758–762.

    PubMed  CAS  Google Scholar 

  77. Dixon JM, Love CDB, Tucker S, Bellamy D, Cameron D, Miller WR, Leonard RCF. Letrozole as primary medical therapy for locally advanced and large operable breast cancer. Breast Cancer Res Treatment 1997; 46:54.

    Google Scholar 

  78. Dixon JM, Love CDB, Tucker S, Bellamy D, Cameron D, Miller WR, Leonard RCF. Letrozole as primary medical therapy for locally advanced breast cancer. Breast 1997; 6:245.

    Article  Google Scholar 

  79. Wolf DM, Jordan VC. William L. McGuire Memorial Symposium. Drug resistance to tamoxifen during breast cancer therapy. Breast Cancer Res Treatment 1993; 27:27–40.

    Article  CAS  Google Scholar 

  80. Jones AL, Powles T, Law M, Tidy A, Easton D, Coombes RC, et al. Adjuvant aminoglutethimide for postmenopausal patients with primary breast cancer: analysis at 8 years. J Clin Oncol 1992; 10:1547–1552.

    PubMed  CAS  Google Scholar 

  81. Santen RT, Samojlik E, Wells SA. Resistance of ovary to blockade of aromatisation with aminoglutethimide. J Clin Endocrinol Metab 1980; 51:473–477.

    Article  PubMed  CAS  Google Scholar 

  82. Harris AL, Dowsett M, Smith IL, Powles TJ. Aminoglutethimide in the treatment of advanced postmenopausal breast cancer. Cancer Res 1982; (Suppl)42:3405–3408.

    Google Scholar 

  83. Wander HE, Blossey HC, Nagel GA. Aminoglutethimide in the treatment of premenopausal patients with metastatic breast cancer. Eur J Cancer 1986; 22:1371–1374.

    Article  CAS  Google Scholar 

  84. Wouters W, de Coster R, Tuman RW, Bowden CR, Bruynseels J, Vanderpas H, Van Rooy P, et al. Aromatase inhibition by R76713. J Steroid Biochem 1989; 34:427–430.

    Article  PubMed  CAS  Google Scholar 

  85. Shetty G, Krishnamurthy H, Krishnamurthy HN, Bhatnagar AS, Moudgal RN. Effect of estrogen deprivation on the reproductive physiology of male and female primates. J Steroid Biochem Mol Biol 1997; 61:157–166.

    Article  PubMed  CAS  Google Scholar 

  86. Miller WR, O’Neill J. The importance of local synthesis of estrogen within the breast. Steroids 1987; 50:537–548.

    Article  PubMed  CAS  Google Scholar 

  87. Santen RJ, Samojlik E, Worgul TJ. Aminoglutethimide product profile, in Pharmanual: A Comprehensive Guide to the Therapeutic Use of Aminoglutethimide (Henderson RSI, ed). Karger, Basel, 1981, pp.101–160.

    Google Scholar 

  88. Miller W. Importance of intratumoural aromatase and its susceptibility to inhibitors, in Aromatase inhibition: then, now and tomorrow. (Dowsett M, ed). Parthenon Publishing New York, 1994, pp 43–53.

    Google Scholar 

  89. Bezwoda WR, MN, Dansey R. Correlation of breast tumour aromatase activity and response to aromatase inhibition with aminoglutethimide. Oncology 1987; 44:345–349.

    Google Scholar 

  90. Santen RJ, Martel J, Hoahland F, Naftolin F, Roa L, Harada N, Hafer L, et al. Stromal spindle cells contain aromatase in human breast tumors. J Clin Endocrinol Metab 1994; 79:627–632.

    Article  PubMed  CAS  Google Scholar 

  91. Sasano H, Nagura H, Harada N, Goukom Y, Kimura M. Immunolocalization of aromatase and other steroidogenic enzymes in breast disorders. Human Pathol 1994; 25:530–535.

    Article  CAS  Google Scholar 

  92. Lu Q, Nakmura J, Savinov A, Yue W, Weisz J, Dabbs DJ, et al. Expression of aromatase protein and messenger ribonucleic acid in tumor epithelial cells and evidence of functional significance of locally produced estrogen in human breast cancers. Endocrinology 1996; 137:3061–3068.

    Article  PubMed  CAS  Google Scholar 

  93. Hamon JT. Loss of hormonal responsiveness in breast cancer, in Endocrine Management of Cancer: Biological Basis (Stoll B, ed). Karger, Basel, 1988, pp 61–71.

    Google Scholar 

  94. Isaacs J. Clinical heterogeneity in relation to response, in Endocrine Management of Cancer: Biological Basis (Stoll B, ed). Karger, Basel, 1988, pp 125–145.

    Google Scholar 

  95. Taylor RE, Powles T, Humphreys J, Bettelheim R, Dowsett M, Casey AJ, et al. Effects of endocrine therapy on steroid receptor content of breast cancer. Br J Cancer 1982; 45:80–85.

    PubMed  CAS  Google Scholar 

  96. Chohan PB, Foster AB, Harland SJ, Jarman M, Leung CS, et al. Metabolism of aminoglutethimide in man; desmolase and aromatase inhibition studies. R Society Med Int Cong Symp Series 1982; 53:19–21.

    Google Scholar 

  97. Strocchi E, Carnaggi CM, Martoni A, Cellerino R, Miseria S, Malacarne P, lndelli M, et al. Aminoglutethimide in advanced breast cancer: plasma levels and clinical results after low and high doses. Cancer Chemother Pharmacol 1991; 27:451–455.

    Article  PubMed  CAS  Google Scholar 

  98. Murray FT, Santner S, Samojlik E, Santen R. Serum aminoglutethimide levels: studies of serum half-life, clearance and patient compliance. J Clin Pharmacol 1989; 19:704–711.

    Google Scholar 

  99. Santens R. Overall experience with aminoglutethimide in the management of advanced breast carcinoma, in Aminoglutethimide: An Alternative Endocrine Therapy for Breast Carcinoma I. (Elsdon-Dew RW, Birdwood GFB, eds). Academic Press, London, 1982, pp 3–7.

    Google Scholar 

  100. Dowsett M, Harris A, Smith IE, Jeffcoate SL. Endocrine changes associated with relapse in advanced breast cancer patients on aminoglutethimide therapy. J Clin Endocrinol Metab 1984; 58:99–104.

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  102. Coombes RC, Goss P, Dowsett M, Gazet J-C, Brodie A. 4-Hydroxyandrostenedione treatment of postmenopausal patients with advanced breast cancer. Lancet 1984; ii:1237–1239.

    Article  Google Scholar 

  103. Bundred NJ, Erenier O, Stewart HJ, Dale BA, Forrest APM. Beneficial response to pituitary ablation following aminoglutethimide. Br J Surg 1986; 73:388–389.

    Article  PubMed  CAS  Google Scholar 

  104. Kadohama N, Yarborough C, Zhou D, Chen S, Osawa Y. Kinetic properties of aromatase mutants Pro308Phe, Asp309Asn and Asp309Ala and their interactions with aromatase inhibitors. J Steroid Biochem Mol Biol 1992; 43:693–701.

    Article  PubMed  CAS  Google Scholar 

  105. Miller W. In vitro and in vivo effects of 4-hydroxyandrostenedione on steroid and tumor metabolism, in 4-Hydroxyandrostenedione: A New Approach to Hormone-Dependent Cancer (DM Coombes RC, ed). Royal Society of Medicine Ltd International Congress and Symposium Series, London, 1992, pp 45–50.

    Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  107. Adams JB, Garda M, Rochefort H. Estrogenic effects of physiological concentrations of 5- androstene-3β,17β-diol and its metabolism in MCF-7 human breast cancer cells. Cancer Res 1981; 41:4720–4726.

    PubMed  CAS  Google Scholar 

  108. Shearer RJ, Hendry W, Sommerville IF, Ferguson JD. Plasma testosterone. An accurate monitor of hormone treatment in prostatic cancer. Br J Urol 1973; 45:668–677.

    Article  PubMed  CAS  Google Scholar 

  109. Blackard GE, Byar DP, Jordan WP. Orchidectomy for advanced prostatic carcinoma. Urology 1973; 1:553–562.

    Article  PubMed  CAS  Google Scholar 

  110. Huggins C. The effect of castration, of estrogen and androgen injection on serum phosphatase in metastatic carcinoma of the prostate. Cancer 1941; 1:293–297.

    CAS  Google Scholar 

  111. Schoonees R, Schalch DS, Reynoso G, Murphy GP. Bilateral adrenalectomy for advanced prostatic carcinoma. J Urol 1972; 108:123–125.

    PubMed  CAS  Google Scholar 

  112. Robinson MRG, Sheaver RJ, Fergusson JD. Adrenal suppression in the treatment of carcinoma of the prostate. Br J Urol 1974; 46:555–559.

    Article  PubMed  CAS  Google Scholar 

  113. Robinson M. Aminoglutethimide: medical adrenalectomy in management of carcinoma of the prostate. A review after six years. Br J Urol 1980; 52:328–329.

    Article  PubMed  CAS  Google Scholar 

  114. Johannessen DC, Lonning PE. Aromatase inhibitors in malignant diseases of aging. Drugs Aging 1992; 2(6):530–545.

    Article  PubMed  CAS  Google Scholar 

  115. Ponder BAJ, Sheaver RJ, Pococ RD, Miller J, Easton D. Response to aminoglutethimide and cortisone acetate in advanced prostatic carcinoma. Br J Cancer 1984; 50:757–763.

    PubMed  CAS  Google Scholar 

  116. Plowman PN, Perry LA, Chard T. Androgen suppression by hydrocortisone without aminoglutethimide in orchidectomised men with prostatic cancer. Br J Urol 1987; 59:255–257.

    Article  PubMed  CAS  Google Scholar 

  117. Dowsett M, Sheaver R, Ponder BAJ, Malone P, Jeffcoate SL. The effects of aminoglutethimide and hydrocortisone, alone and combined, on androgen levels in post-orchidectomy prostatic cancer patients. Br J Cancer 1988; 57:190–292.

    PubMed  CAS  Google Scholar 

  118. Brodie AMH, Son C, King DA, Meyer KM, Inkster SE. Lack of evidence for aromatase in human prostatic tissues: effects of 4-hydroxyandrostenedione and other inhibitors on androgen metabolism. Cancer Res 1989; 49:6551–6555.

    PubMed  CAS  Google Scholar 

  119. Bashirelahi N, Sidh SM, Sanefuji H. Androgen, estrogen and their distribution in epithelial and stromal cells of human prostate, in Steroid Receptors, Metabolism and Prostatic Cancer (De Voogt S, eds). Excerpta Medica, Amsterdam, 1990, pp 240–255.

    Google Scholar 

  120. Shearer RJ, Davies JH, Dowsett M, Malone PR, Hedley A. Aromatase inhibition in advanced prostatic cancer: preliminary communication. Br J Cancer 1990; 62:275–276.

    PubMed  CAS  Google Scholar 

  121. Pirke KM, Doerr P. Age related changes and interrelationship between plasma testosterone, estradiol and testosterone binding globulin in normal adult males. Acta Endocrinol 1973; 74:792–800.

    PubMed  CAS  Google Scholar 

  122. Seppel U. Correlation among prostate stroma, plasma estrogen levels and urinary estrogen excretion in patients with benign prostatic hypertrophy. J Clin Endocrinol Metab 1978; 47:1230–1235.

    Article  Google Scholar 

  123. Ranniko S, Adlercreutz H. Plasma estradiol, free testosterone, sex hormone binding globulin and prolactin in benign prostatic hyperplasia and prostate cancer. Prostate 1983; 4:223–229.

    Article  Google Scholar 

  124. Habernicht UF, Schwarz K, Schweikert HU, Neumann F, El Etreby MF. Development of a model for the induction of estrogen-related prostatic hyperplasia in the dog and its response to the aromatase inhibitor 4-hydroxy-4-androstene-3,17-dione: preliminary results. Prostate 1986; 8:181–194.

    Article  Google Scholar 

  125. Habernicht UF, Schwarz K, Neumann F, El Etreby MF. Induction of estrogen-related hyperplastic changes in the prostate of the cynomolgus monkey (Macaca fascicularis) by androstenedione and its antagonism by the aromatase inhibitor 1-methyl-androsta-l,4- diene-3,17-dione. Prostate 1987; 11:313–326.

    Article  Google Scholar 

  126. Habernicht UF, El Etreby F, Lewis R, Ghoniem G, Roberts J. Induction of metachromasia in experimentally induced hyperplastic/hypertrophic changes in the prostate of the cynomolgus monkey (Macaca fascicularis). J Urol 1989; 142:1624–1626.

    Google Scholar 

  127. Moore RA, McLellan AM. A histological study of the effect of sex hormones on the human prostate. J Urol 1938; 40:641–657.

    Google Scholar 

  128. Khanna Om P. Effect of nonautonomic drugs on the vesical neck, in Benign Prostatic Hypertrophy (Hinman F, ed). Springer-Verlag, New York, 1983, pp 384–404.

    Google Scholar 

  129. Habernicht U-F, Tunn UW, Senge T, Schroder FH, Schweikert HU, Bartsch G, El Etreby MF. Management of Benign Prostatic Hyperplasia with particular emphasis on aromatase inhibitors. J Steroid Biochem Mol Biol 1993; 44:557–563.

    Article  Google Scholar 

  130. Schweikert HU, Tunn UW. Effects of the aromatase inhibitor testolactone on human benign prostatic hyperplasia. Steroids 1987; 50:191–200.

    Article  PubMed  CAS  Google Scholar 

  131. Schweikert HU, Tunn UW, Habenicht UF, Amold J, Senge T, Schulze H, et al. Effects of estrogen deprivation on human benign prostatic hyperplasia. J Steroid Biochem Mol Biol 1993; 44:573–576.

    Article  PubMed  CAS  Google Scholar 

  132. Gingell JC, Knogagel H, Kurth KH, Tunn UW. Placebo controlled double-blind study to test the efficacy of the aromatase inhibitor atamestane in patients with benign prostatic hyperplasia not requiring operation. J Urol 1995; 154:402–403.

    Article  Google Scholar 

  133. Radlmaier A, Erkenberg HU, Fletcher MS, Fourcade RO, Reis-Santos JM, van Aubel OG, Bono AV. Estrogen reduction by aromatase inhibition for benign prostatic hyperplasia: results of a double-blind, placebo-controlled, randomized clinical trial using two doses of the aromatase inhibitor atamestane. Prostate 1996; 29(4):199–208.

    Article  PubMed  CAS  Google Scholar 

  134. Pollow K, Lubbert H, Boquoi E, Kreuyzer G, Pollow B. Characterisation and comparison of receptors for 17β-estradlol and progesterone in human proliferative endometrium and endometrial carcinoma. Endocrinology 1975; 96:319–328.

    Article  PubMed  CAS  Google Scholar 

  135. Yamamoto T, Kitawaki J, Urabe M, Honjo H, Tamura T, Noguchi T, et al., Estrogen productivity of endometrium and endometrial cancer tissue; influence of aromatase on proliferation of endometrial cancer cells. J Steroid Biochem Mol Biol 1993; 44:463–468.

    Article  PubMed  CAS  Google Scholar 

  136. Quinn MA, Murray R, Pepperell RJ. Tamoxifen and aminoglutethimide in the management of patients with advanced endometrial carcinoma not responsive to medroxyprogesterone. Aust N Zeal J Obstet Gynaecol 1981; 21:226–229.

    Article  CAS  Google Scholar 

  137. Yamamoto T, Tamura T, Kitiwaki J, Okada H. Evidence for estrogen synthesis in adenomyotic tissues. Am J Obstet Gynecol 1993; 69:734–738.

    Google Scholar 

  138. Yano S, IY, Nakao K. Studies on the effect of the new non-steroidal aromatase inhibitor fadrozole hydrochloride in an endometriosis model in rats. Arzneimittelforschung 1996; 46:92–195.

    Google Scholar 

  139. Takayama K, Zeitoun K, Gunby RT, Sasano H, Carr BR, Bolun SE. Treatment of severe postmenopausal endometriosis with an aromatase inhibitor. Fertil Steril 1998; 69:709–713.

    Article  PubMed  CAS  Google Scholar 

  140. Santen RJ, Santner S, Harvey HA, Lipton A, Simmons M, et al. Marked heterogeneity of aromatase activity in human malignant melanoma tissue. Eur J Cancer Clin Oncol 1988; 24:1811–1816.

    Article  PubMed  CAS  Google Scholar 

  141. Harvey H, Lipton A, Simmons M, Santen R, Bartholomew M. Chemotherapy and aromatase inhibition in metastatic malignant melanoma. Proc Am Society Clin Oncol 1988; 7:A978.

    Google Scholar 

  142. Block S, Bonneterre J, Adenis A, Pion JM, Demaille A. Aminoglutethimide in malignant melanoma. A phase II study. Am J Clin Oncol 1992; 15(3):260–261.

    Article  PubMed  CAS  Google Scholar 

  143. Hemsell DL, Edman CD, Marks IF, Siiteri PK, MacDonald PC. Massive extraglandular aromatization of plasma androstenedione resulting in feminization of a prepubertal boy. J Clin Invest 1977; 60:455–464.

    Article  PubMed  CAS  Google Scholar 

  144. Berkovitz GD, Guerami A, Brown TR, MacDonald PC, Migeon CJ. Farr gynaecomastia with increased extraglandular aromatization of plasma C19-steroids. J Clin Invest 1985; 75:1763–2769.

    Article  PubMed  CAS  Google Scholar 

  145. Bulun SE, Noble LS, Takayama K, Dodson MM, Agarwal V, Fisher C, et al. Endocrine disorders associated with inappropriately high aromatase expression. J Steroid Biochem Mol Biol 1997; 61:133–139.

    Article  PubMed  CAS  Google Scholar 

  146. Bulun S. Endocrinopathies associated with excessive aromatase expression. Program and Abstracts, 4th International Aromatase Conference, p S-6.

    Google Scholar 

  147. Feinlieb M. Breast cancer and artificial menopause: a cohort study. J Nat Cancer Inst 1968; 41:315–329.

    Google Scholar 

  148. Thomas HV, Key T, Allen DS, Moore JW, Dowsett M, Fentiman IS, et al. A prospective study of endogenous serum hormone concentration and breast cancer risk in postmenopausal women on the island of Guernsey. Br J Cancer 1997; 76(3):401–405.

    PubMed  CAS  Google Scholar 

  149. Nissen-Meyer, R. Primary breast cancer: the effect of primary ovarian irradiation Ann Oncol 1991; 2:34–346.

    Google Scholar 

  150. Cuzik J, Baum M. Tamoxifen and contralateral breast cancer. Lancet 1985; 2:28.

    Google Scholar 

  151. Powles TJ, Hardy J, Ashley SE, Cosgrove D, Davey JH, Dowsett M, McKinna JA, et al. Chemoprevention of breast cancer. Breast Cancer Res Treatment 1989; 14:23–31.

    Article  CAS  Google Scholar 

  152. Gunson DE, Steele RE, Chau RY Prevention of tumours in female rats by fadrozole, an aromatase inhibitor. Br J Cancer 1995; 72:72–75.

    PubMed  CAS  Google Scholar 

  153. Durgam VR, Tekmal RR. The nature and expression of int-5, a novel MMTV integration locus gene in carcinogen-induced tumors. Cancer Lett 1994; 87:179–286.

    Article  PubMed  CAS  Google Scholar 

  154. Siegelmann-Danieli N, Zidan J, McGlynn KA, Buetow KH. DNA-based variation at the aromatase gene (CYP1B) and its role in breast cancer susceptibility. Proc Am Society Clin Oncol 1996; 15:23.

    Google Scholar 

  155. Boccuzi G, Brignardello E, Dimonaco D, Forte C, Leonardi L, Pizzini A. Influence of dehydroepiandrosterone and 5-en-androstene-3-beta, 17-beta-diol on the growth of MCF-7 human breast cancer cells induced by 17-beta estcadiol. Anticancer Res 1992; 12:799–803.

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Academic Department of Biochemistry, Royal Marsden Hospital, London, UK

    K. Shenton, Mitchell Dowsett & Michael Dukes

Authors
  1. K. Shenton
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Mitchell Dowsett
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Michael Dukes
    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

© 2002 Humana Press, a part of Springer Science+Business Media, LLC

About this chapter

Cite this chapter

Shenton, K., Dowsett, M., Dukes, M. (2002). Clinical Utility of Aromatase Inhibitors. 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_12

Download citation

  • DOI: https://doi.org/10.1007/978-1-59259-152-7_12

  • 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