The therapeutic potential of aromatase inhibitors

Expert Opinion on Investigational Drugs

Volumn 12, Issue 3, 2003, Pages 337-351

  Miller, W R ^a   Jackson, J ^b  

^a UNIVERSITY OF EDINBURGH   (United Kingdom)

^b WESTERN GENERAL HOSPITAL   (United Kingdom)

Author keywords

Aromatase inhibitors; Breast cancer; Endocrine; Oestrogen; Therapeutic

Indexed keywords

AMINOGLUTETHIMIDE; ANASTROZOLE; ANDROGEN; ANDROSTENEDIONE; ANTIESTROGEN; AROMATASE; AROMATASE INHIBITOR; BISPHOSPHONIC ACID DERIVATIVE; CORTICOSTEROID; CYTOCHROME P450; ESTRADIOL; ESTROGEN; ESTROGEN RECEPTOR; ESTRONE; EXEMESTANE; FADROZOLE; FORMESTANE; GESTAGEN; IMIDAZOLE; LETROZOLE; LUTEINIZING HORMONE; MEGESTROL ACETATE; PROSTAGLANDIN E2; STEROID 11BETA MONOOXYGENASE; STEROID 21 MONOOXYGENASE; TAMOXIFEN; TESTOLACTONE; TESTOSTERONE; TRIAZOLE; UNINDEXED DRUG;

ADJUVANT THERAPY; BREAST CANCER; CANCER INCIDENCE; CANCER STAGING; CANCER SURVIVAL; CELL HYPERPLASIA; CEREBROVASCULAR DISEASE; CHEMOPROPHYLAXIS; CLINICAL TRIAL; DEEP VEIN THROMBOSIS; DRUG ABSORPTION; DRUG EFFICACY; DRUG MECHANISM; DRUG METABOLISM; DRUG POTENCY; DRUG STRUCTURE; ENDOMETRIOSIS; ENDOMETRIUM CANCER; ENZYME INHIBITION; ESTROGEN BLOOD LEVEL; ESTROGEN SYNTHESIS; FIBROADENOMA; GENOTOXICITY; GYNECOMASTIA; HORMONE SUBSTITUTION; HOT FLUSH; HUMAN; LEYDIG CELL; LUTEINIZING HORMONE RELEASE; MASTALGIA; MENOPAUSAL SYNDROME; MUSCULOSKELETAL DISEASE; NONHUMAN; PROSTATE CANCER; RECURRENT DISEASE; REVIEW; THROMBOEMBOLISM; VAGINAL DRYNESS;

ANIMALS; ANTINEOPLASTIC AGENTS; AROMATASE; AROMATASE INHIBITORS; BREAST NEOPLASMS; CLINICAL TRIALS; DRUG THERAPY, COMBINATION; ENZYME INHIBITORS; ESTROGEN ANTAGONISTS; HUMANS; NEOPLASMS, HORMONE-DEPENDENT; TAMOXIFEN;

EID: 0037340808     PISSN: 13543784     EISSN: None     Source Type: Journal    
DOI: 10.1517/13543784.12.3.337     Document Type: Review

References (78)

1. MILLER WR: Estrogens and breast cancer. In: Estrogen and Breast Cancer. RG Landes Company, Austen, TX, USA (1996):1-24.
2. MILLER WR, LANGDON SP: Steroid hormones and cancer: (III) observations from human subjects. Eur. J. Surg. Oncol. (1977) 23(2):163-183.
3. WELLS SA Jr, SANTEN RJ, LIPTON A et al.:. Medical adrenalectomy with aminoglutethimide: clinical studies in postmenopausal patients with metastatic breast carcinoma. Ann. Surg. (1978) 187(5):475-484.
4. SANTEN RJ, SAMOJLIK E, WORGUL TJ: Aminoglutethimide - product profile. In: A Comprehensive Guide to the Therapeutic Use of Aminoglutethimide. RJ Santen, IC Henderson (Eds), Karger, Basel, Switzerland (1981):101-160.
5. JOHANNESSEN DC, ENGAN T, DI SALLE E et al.: 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. (1997) 3(7):1101-1108.
6. JOHNSTON JO, METCALF BW: Aromatase: a target enzyme. In: Novel Approaches to Cancer Chemotherapy, London Academic Press (1984):307-328.
7. DIXON JM: Exemestane: a potent irreversible aromatase inactivator and a promising advance in breast cancer treatment. Expert Rev. Anti-Cancer Ther. (2002) 2(3):267-275.
8. SANTEN RJ, MISBIN RI: Aminoglutethimide: review of pharmacology and clinical use. Pharmacotherapy (1981) 1(2):95-120.
9. VAN DEN BOSSCHE HV, MOEREELS H, KOYMANS LM: Aromatase inhibitors-mechanisms for non-steroidal inhibitors. Breast Cancer Res. Treat. (1994) 30(1):43-55.
10. BARONE RM, SHAMONKI IM, SIITERI PK, JUDD HL: Inhibition of peripheral aromatization of androstenedione to estrone in postmenopausal women with breast cancer using delta 1-testololactone. J. Clin. Endocrinol. Metab. (1979) 49(5):672-676.
11. 1-Testololactone: clinical trials. Can. Res. (1982) Suppl. 42:3387-3388.
12. GRIFFITHS CT, HALL TC, SABA Z, BARLOW JJ, NEVINNY HB: Preliminary trial of aminoglutethimide in breast cancer. Cancer (1973) 32:31-37.
13. CUNNINGHAM D, POWLES TJ, DOWSETT M et al.: Oral 4-hydroxyandrostenedione, a new endocrine treatment for disseminated breast cancer. Cancer Chemother. Pharmacol. (1987) 20(3):253-255.
14. 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.
15. MILLER WR: Biology of aromatase inhibitors: pharmacology/endocrinology within the breast. Endocr. Relat. Cancer (1999) 6(2):187-195.
16. DOWSETT M: Drug and hormone interactions of aromatase inhibitors. Endocr. Relat. Cancer (1999) 6(2):181-185.
17. MILLER WR, MULLEN P, SOURDAINE P, WATSON C, DIXON JM, TELFORD J: Regulation of aromatase activity within the breast. J. Steroid Biochem. Mol. Biol. (1997) 61(3-6):193-202.
18. BHATNAGAR A, MILLER WR: Pharmacology of inhibitors or estrogen biosynthesis. In: Estrogens and Anti-Estrogens II: Pharmacology and Clinical Applications of Estrogens and Anti-Estrogens. Oertel M, Schillinger E (Eds), Springer-Verlag, Berlin, Germany (1999):223-230.
19. KAO YC, OKUBO T, SUN XZ, CHEN S: Induction of aromatase expression by aminoglutethimide, an aromatase inhibitor that is used to treat breast cancer in postmenopausal women. Anti-Cancer Res. (1999) 19(3A):2049-2056.
20. CHEN S, ZHOU D, OKUBO T, KAO YC, YANG C: Breast tumor aromatase: functional role and transcriptional regulation. Endocr. Relat. Cancer (1999) 6(2):149-156.
21. HARADA N, HONDA SI, HATANO O: Aromatase inhibitors and enzyme stability. Endocr. Relat. Cancer (1999) 6(2):211-218.
22. MILLER WR, O'NEILL J: The importance of local synthesis of estrogen within the breast. Steroids (1987) 50(4-6):537-548.
23. MILLER WR, VIDYA R, MULLEN P, DIXON JM: Induction and suppression of aromatase by inhibitors. In: Aromatase Inhibition and Breast Cancer. WR Miller and RJ Santen (Eds), Marcel Dekker Inc., New York (2000):213-225.
24. LONNING PE: Pharmacology of new aromatase inhibitors. Breast (2001) 5:202-208.
25. DOWSETT M: Aromatase inhibition: the outcome of 20 years of drug development. In: Aromatase Inhibition and Breast Cancer. WR Miller, RJ Santen (Eds), Marcel Dekker Inc., New York (2001):3-15.
26. YATES RA, DOWSETT M, FISHER GV, SELEN A, WYLD PJ: Arimidex (ZD1033): a selective, potent inhibitor of aromatase in postmenopausal female volunteers. Br. J. Cancer (1996) 73(4):543-548.
27. DEMERS LM, LIPTON A, HARVEY HA et al.: The efficacy of CGS 20267 in suppressing estrogen biosynthesis in patients with advanced stage breast cancer. J. Steroid Biochem. Mol. Biol. (1993) 44(4-6):687-691.
28. THURLIMANN B, PARIDAENS R, SERIN D et al.: Third-line hormonal treatment with exemestane in postmenopausal patients with advanced breast cancer progressing on aminoglutethimide: a Phase II multicentre multinational study. Exemestane Study Group. Eur. J. Cancer (1997) 33(11):1767-1773.
29. 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 advanced breast cancer. Cancer Res. (1993) 15;53(2):266-270.
30. LONNING PE, KVINNSLAND S: Mechanisms of action of aminoglutethimide as endocrine therapy of breast cancer. Drugs (1988) 35(6):685-710.
31. GROOM GV, GRIFFITHS K: Effect of the anti-oestrogen tamoxifen on plasma levels of lutenizing hormone, follicle stimulating hormone, prolactin, oestradiol and progesterone in normal premenopausal women. J. Endocrinol. (1976) 70:421-428.
32. O'REGAN RM, JORDAN VC: The evolution of tamoxifen therapy in breast cancer: selective oestrogen-receptor modulators and downregulators. Lancet Oncol. (2002) 3(4):207-214.
33. MILLER WR, DIXON JM, MACFARLANE L, CAMERON D, ANDERSON TJ: Pathological features of breast cancer response following neoadjuvant treatment with either letrozole or tamoxifen. Eur. J. Cancer (2002) (In press).
34. LIPTON A, DEMERS LM, HARVEY HA et al.: Letrozole (CGS 20267). A Phase I study of a new potent oral aromatase inhibitor of breast cancer. Cancer (1995) 15;75(8):2132-2138.
35. JOHNSTON SR, HAYNES BP, SACKS NP et al.: 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. (1993) 28(3):241-250.
36. JONAT W, HOWELL A, BLOMQVIST C et al.: A randomised trial comparing two doses of the new selective aromatase inhibitor anastrozole (Arimidex) with megestrol acetate in postmenopausal patients with advanced breast cancer. Eur. J. Cancer (1996) 32A(3):404-412.
37. BUZDAR A, JONAT W, HOWELL A 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. Arimidex Study Group. J. Clin. Oncol. (1996) 14(7):2000-2011.
38. GERSHANOVICH M, CHAUDRI HA, CAMPOS D et al.: Letrozole, a new oral aromatase inhibitor: randomised trial comparing 2.5 mg daily, 0.5 mg daily and aminoglutethimide in postmenopausal women with advanced breast cancer. Letrozole International Trial Group (AR/BC3). Ann. Oncol. (1998) 9(6):639-645.
39. DOMBERNOWSKY P, SMITH I, FALKSON G 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(2):453-461.
40. KAUFMANN M, BAJETTA E, DIRIX LY et al.: Exemestane is superior to megestrol acetate after tamoxifen failure in postmenopausal women with advanced breast cancer: results of a Phase III randomized double-blind trial. The Exemestane Study Group. J. Clin. Oncol. (2000) 18(7):1399-1411.
41. BUZDAR A, DOUMA J, DAVIDSON N et al.: Phase III, multicenter, double-blind, randomized study of letrozole, an aromatase inhibitor, for advanced breast cancer versus megestrol acetate. J. Clin. Oncol. (2001) 19(14):3357-3366.
42. ROSE C, VTORAYA O, PLUZANSKA A et al.: Letrozole (Femara) versus anastrozole (Arimidex): second-line treatment in postmenopausal women with advanced breast cancer. 38th Annual Meeting of the American Society of Clinical Oncology, Orlando, FL, USA (2002) (Abstract 131).
43. JONES S, CHANG A, LUSCH C et al.: A Phase II confirmatory study of antitumor efficacy and safety of exemestane (EXE) as third-line hormonal treatment of postmenopausal patients (pts) with metastatic breast cancer (MBC) refractory to tamoxifen and Megace™. Breast Cancer Res. Treat. (1998) 50:305 (Abstract 437).
44. JONES S, VOGEL C, ARKHIPOV A et al.: Multicenter, Phase II trial of exemestane as third-line hormonal therapy of postmenopausal women with metastatic breast cancer. Aromasin Study Group. J. Clin. Oncol. (1999) 17:3418-3425.
45. LONNING PE, BAJETTA E, MURRAY R et al.: Activity of exemestane in metastatic breast cancer after failure of nonsteroidal aromatase inhibitors: a Phase II trial. J. Clin. Oncol. (2000) 18:2234-2244.
46. BUZDAR AU, JONAT W, HOWELL A et al.: Anastrozole versus megestrol acetate in the treatment of postmenopausal women with advanced breast carcinoma: results of a survival update based on a combined analysis of data from two mature Phase III trials. Arimidex Study Group. Cancer (1998) 83(6):1142-1152.
47. MOURIDSEN H, GERSHANOVICH M, SUN Y et al.: 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. (2001) 19(10):2596-2606.
48. MOURIDSEN H, SUN Y, GERSHANOVICH M et al.: 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. (2001) 69:211.
49. NABHOLTZ JM, BUZDAR A, POLLAK M et al.: 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. (2000) 18(22):3758-3767.
50. BONNETERRE J, THURLIMANN B, ROBERTSON JF et al.: Anastrozole versus tamoxifen as first-line therapy for advanced breast cancer in 668 postmenopausal women: results of the Tamoxifen or Arimidex Randomized Group Efficacy and Tolerability study. J. Clin. Oncol. (2000) 18(22):3748-3757.
51. DIXON JM, LOVE CD, BELLAMY CO et al.: Letrozole as primary medical therapy for locally advanced and large operable breast cancer. Breast Cancer Res. Treat. (2001) 66(3):191-199.
52. GOSS PE, STRASSER K: Aromatase inhibitors in the treatment and prevention of breast cancer. J. Clin. Oncol. (2001) 19(3):881-894.
53. DIXON JM, RENSHAW L, BELLAMY C, STUART M, HOCTIN-BOES G, MILLER WR: The effects of neoadjuvant anastrozole (Arimidex) on tumor volume in postmenopausal women with breast cancer: a randomized, double-blind, single-center study. Clin. Cancer Res. (2000) 6(6):2229-2235.
54. DIXON JM, ANDERSON TJ, MILLER WR: Neoadjuvant endocrine therapy of breast cancer: a surgical perspective. Eur. J. Cancer (2002) 38(17):2214-2221.
55. ANDERSON TJ, DIXON JM, STUART M, SAHMOUD T, MILLER WR: Effect of neoadjuvant treatment with anastrozole on tumour histology in postmenopausal women with large operable breast cancer. Br. J. Cancer (2002) 87:334-338.
56. EIERMANN W, PAEPKE S, APPFELSTAEDT J: Letrozole Neo-Adjuvant Breast Cancer Study Group. Preoperative treatment of postmenopausal breast cancer patients with letrozole: A randomized double-blind multicenter study. Ann. Oncol. (2001) 12(11):1527-1532.
57. GOSS P: Anti-aromatase agents in the treatment and prevention of breast cancer. Cancer Control (2002) 9(2, Suppl.):2-8.
58. GOSS P: Chemoprevention with aromatase inhibitors. In: Aromatase Inhibition and Breast Cancer. WR Miller, RJ Santen (Eds), Marcel Dekker Inc., New York (2001):161-181.
59. The ATAC Trialists' Group: 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 (2002) 359(9324):2131-2139.
60. The ATAC Trialists' Group: Pharmacokinetics of anastrozole and tamoxifen alone, and in combination, during adjuvant endocrine therapy for early breast cancer in postmenopausal women: a sub-group of the 'Arimidex' and Tamoxifen Alone or in Combination (ATAC) trial. Br. J. Cancer (2001) 85:317-324.
61. ELISAF MS, BAIRAKTARI ET, NICOLAIDES C et al.: Effect of letrozole on the lipid profile in postmenopausal women with breast cancer. Eur. J. Cancer (2001) 37:1510-1513.
62. DEWAR J, NABHOLTZ JM, BONNETERRE J, BUZDAR AU: The effect of anastrozole (Arimidex) on serum lipids: a randomised comparison of anastrozole (AN) versus tamoxifen (TAM) in postmenopausal women with advanced breast cancer. Eur. J. Cancer (2001) 37(Suppl. 5):5.
63. THOMAS HV, KEY TJ, ALLEN DS et al.: A prospective study of endogenous serum hormone concentrations and breast cancer risk in post-menopausal women on the island of Guernsey. Br. J. Cancer (1997) 76(3):401-405.
64. MILLER WR: Estrogens and endocrine therapy for breast cancer. In: Estrogen and Breast Cancer. RG Landes Company, Austen, TX, USA (1996):125-150.
65. FISHER B, COSTANTINO JP, WICKERHAM DL et al.: Tamoxifen for prevention of breast cancer: report of the National Surgical Adjuvant Breast and Bowel Project P-1 Study. J. Natl. Cancer Inst. (1998) 90(18):1371-1388.
66. YAGER JD, LIEHR JG: Molecular mechanisms of estrogen carcinogenesis. Ann. Rev. Pharmacol. Toxicol. (1996) 36:203-232.
67. GOSS PE: Aromatase inhibitors and chemoprevention of breast cancer. In: Endocrine Therapy in Breast Cancer. WR Miller, JN Ingle (Eds). Marcel Dekker, Basel, CH (2002):309-317.
68. SANTEN RJ, YUE W, NAFTOLIN F, MOR G, BERSTEIN L: The potential of aromatase inhibitors in breast cancer prevention. Endocr. Relat. Cancer (1999) 6(2):235-243.
69. HARRIS AL, DOWSETT M, JEFFCOATE SL, MCKINNA JA, MORGAN M, SMITH IE: Endocrine and therapeutic effects of aminoglutethimide in premenopausal patients with breast cancer. J. Clin. Endocrinol. Metab. (1982) 55(4):718-722.
70. KAPLOWITZ PB: Aromatase inhibitors as therapy for pubertal gynecomastia. In: Aromatase Inhibition and Breast Cancer. WR Miller, RJ Santen (Eds), Marcel Dekker Inc., New York (2001):259-266.
71. BULUN SE, ZEITON KM, TAKAYAMA K, SASANO H, SIMPSON ER: Aromatase in endometriosis: biological and clinical application. In: Aromatase Inhibition and Breast Cancer. WR Miller, RJ Santen (Eds), Marcel Dekker Inc., New York (2001):279-298.
72. BOWMAN A, GABRA H, LANGDON SP et al.: CA125 Response is associated with estrogen receptor expression in a Phase II Trial of letrozole in ovarian cancer: identification of an endocrine-sensitive subgroup. Clin. Cancer Res. (2002) 8(7):2233-2239.
73. SMITH MR: Aromatase inhibition and prostate cancer. In: Aromatase Inhibition and Breast Cancer. WR Miller, RJ Santen (Eds), Marcel Dekker Inc., New York (2001):271-278.
74. BULARD J, MOWSZOWICZ I, SCHAISON G: Increased aromatase activity in pubic skin fibroblasts from patients with isolated gynecomastia. J. Clin. Endocrinol. Metab. (1987) 64(3):618-623.
75. ZACHMANN M, EIHOLZER U, MURITANO M, WERDER EA, MANELLA B: Treatment of pubertal gynaecomastia with testolactone. Acta Endocrinol. Suppl. (Copenh.) (1986) 279:218-226.
76. JUNKER WALKER U, NOGUES V: Changes induced by treatment with aromatase inhibitors in testicular Leydig cells of rats and dogs. Exp. Toxicol. Pathol. (1994) 46(3):211-213.
77. DEARNALEY DP, SHERARER RJ, GALLACHER C et al.: A Phase (Ph) I/II study with rogletimide (ROG) in patients (pt) with hormone resisitant (HR) prostatic cancer (CaP) (meeting abstr). Ann. Oncol. (1995) (Suppl. 8):179.
78. TAKAYAMA K, ZEITOUN K, GUNBY RT, SASANO H, CARR BR, BULUN SE: Treatment of severe postmenopausal endometriosis with an aromatase inhibitor. Fertil. Steril. (1998) 69(4):709-713.