Aromatase inhibitors in the treatment of breast cancer

Endocrine Reviews

Volumn 26, Issue 3, 2005, Pages 331-345

  Brueggemeier, Robert W ^a,b   Hackett, John C ^a   Diaz Cruz, Edgar S ^a  

^a OHIO STATE UNIVERSITY   (United States)

^b OHIO STATE UNIVERSITY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

10 PROPARGYLESTR 4 ENE 3,17 DIONE; 7 ALPHA PHENETHYL ANDROSTA 1,4 DIENE 3,17 DIONE; 7 ALPHA SUBSTITUTED ARYLALIPHATIC ANDROST 4 ENE 3,17 DIONE; 7ALPHA (4 AMINOPHENYLTHIO)ANDROSTENEDIONE; ALPHA NAPHTHOFLAVONE; AMINOGLUTETHIMIDE; ANASTROZOLE; ANDROGEN; APIGENIN; AROMATASE INHIBITOR; ATAMESTANE; BIOCHANIN A; CELECOXIB; CHRYSIN; CYTOCHROME P450; CYTOKINE; ESTRADIOL; EXEMESTANE; FADRAZOLE; FLAVANONE; FLAVONOID; FORMESTANE; GLUCOCORTICOID; IMIDAZOLE; LETROZOLE; MEGESTROL ACETATE; PROSTAGLANDIN E2; QUERCETIN; RADIOISOTOPE; TAMOXIFEN; TRIAZOLE DERIVATIVE; UNCLASSIFIED DRUG; VOROZOLE;

BREAST CANCER; BREAST METASTASIS; CLINICAL TRIAL; DRUG EFFICACY; DRUG POTENCY; ESTROGEN SYNTHESIS; ESTROGEN THERAPY; FRACTURE; GENE EXPRESSION; GROWTH STIMULATION; HUMAN; OSTEOPOROSIS; POSTMENOPAUSE; PRIORITY JOURNAL; REVIEW;

ANIMALS; ANTINEOPLASTIC AGENTS; AROMATASE; AROMATASE INHIBITORS; BREAST NEOPLASMS; CLINICAL TRIALS; ESTROGENS; FEMALE; HUMANS; NEOPLASMS, HORMONE-DEPENDENT;

EID: 18844443185     PISSN: 0163769X     EISSN: None     Source Type: Journal    
DOI: 10.1210/er.2004-0015     Document Type: Review

References (166)

1. American Cancer Society 2004 Facts and figures. Atlanta: American Cancer Society
2. Weigel NL, Rowan BG 2001 Estrogen and progesterone action. In: DeGroot LJ, Jameson JL, Burger HG, et al, eds. Endocrinology. Philadelphia: WB Saunders; 2053-2060
3. Dickson RB, Lippman ME 1995 Molecular basis of breast cancer. In: Mendelsohn J, Howley PH, Israel MA, Liotta LA, eds. The molecular basis of cancer. Philadelphia: WB Saunders; 358-386
4. Simpson ER, Mahendroo MS, Means GD, Kilgore MW, Hinshelwood MM, Graham-Lorence S, Amarneh B, Ito Y, Fisher CR, Michael MD 1994 Aromatase cytochrome P450, the enzyme responsible for estrogen biosynthesis. Endocr Rev 15:342-355
5. James VH, McNeill JM, Lai LC, Newton CJ, Ghilchik MW, Reed MJ 1987 Aromatase activity in normal breast and breast tumor tissues: in vivo and in vitro studies. Steroids 50:269-279
6. Miller WR, O'Neill J 1987 The importance of local synthesis of estrogen within the breast. Steroids 50:537-548
7. Reed MJ, Owen AM, Lai LC, Coldham NG, Ghilchik MW, Shaikh NA, James VH 1989 In situ oestrone synthesis in normal breast and breast tumour tissues: effect of treatment with 4-hydroxyandrostenedione. Int J Cancer 44:233-237
8. Bulun SE, Price TM, Aitken J, Mahendroo MS, Simpson ER 1993 A link between breast cancer and local estrogen biosynthesis suggested by quantification of breast adipose tissue aromatase cytochrome P450 transcripts using competitive polymerase chain reaction after reverse transcription. J Clin Endocrinol Metab 77:1622-1628
9. Simpson ER, Mahendroo MS, Means GD, Kilgore MW, Corbin CJ, Mendelson CR 1993 Tissue-specific promoters regulate aromatase cytochrome P450 expression. J Steroid Biochem Mol Biol 44:321-330
10. Kellis JT, Vickery LE 1987 Purification and characterization of human placental aromatase cytochrome P-450. J Biol Chem 262: 4413-4420
11. Akhtar M, Calder MR, Corina DL, Wright JN 1982 Mechanistic studies on C-19 demethylation in oestrogen biosynthesis. Biochem J 201:569-580
12. Graham-Lorence S, Amarneh B, White RE, Peterson JA, Simpson ER 1995 A three-dimensional model of aromatase cytochrome P450. Protein Sci 4:1065-1080
13. Hackett JC, Brueggemeier RW, Haddad CM 2005 The final catalytic step of cytochrome P450 aromatase: a density functional theory study. J Am Chem Soc 10.1021/ja044716w
14. Meunier B, de Visser SP, Shaik S 2004 Mechanism of oxidation reactions catalyzed by cytochrome p450 enzymes. Chem Rev 104:3947-3980
15. Bulun SE, Takayama K, Suzuki T, Sasano H, Yilmaz B, Sebastian S 2004 Organization of the human aromatase p450 (CYP19) gene. Semin Reprod Med 22:5-9
16. Gartner CA, Thompson SJ, Rettie AE, Nelson SD 2001 Human aromatase in high yield and purity by perfusion chromatography and its characterization by difference spectroscopy and mass spectrometry. Protein Expr Purif 22:443-454
17. Zhao Y, Agarwal VR, Mendelson CR, Simpson ER 1997 Transcriptional regulation of CYP19 gene (aromatase) expression in adipose stromal cells in primary culture. J Steroid Biochem Mol Biol 61:203-210
18. Simpson ER, Clyne C, Rubin G, Boon WC, Robertson K, Britt K, Speed C, Jones M 2002 Aromatase - a brief overview. Annu Rev Physiol 64:93-127
19. Dowsett M, Macaulay V, Gledhill J, Ryde C, Nicholls J, Ashworth A, McKinna JA, Smith IE 1993 Control of aromatase in breast cancer cells and its importance for tumor growth. J Steroid Biochem Mol Biol 44:605-609
20. Miller WR, Mullen P, Bourdaine P, Watson C, Dixon JM, Telford J 1997 Regulation of aromatase activity within the breast. J Steroid Biochem Mol Biol 61:193-202
21. Reed MJ, Topping L, Coldham NG, Purohit A, Ghilchik MW, James VH 1993 Control of aromatase activity in breast cancer cells: the role of cytokines and growth factors. J Steroid Biochem Mol Biol 44:589-596
22. Quinn AL, Burak WE, Brueggemeier RW 1999 Effects of matrix components on aromatase activity in breast stromal cells in culture. J Steroid Biochem Mol Biol 70:249-256
23. Sasano H, Edwards DP, Anderson TJ, Silverberg SG, Evans DB, Santen RJ, Ramage P, Simpson ER, Bhatnagar AS, Miller WR 2003 Validation of new aromatase monoclonal antibodies for immunohistochemistry: progress report. J Steroid Biochem Mol Biol 86:239-244
24. Zhao Y, Agarwal VR, Mendelson CR, Simpson ER 1996 Estrogen biosynthesis proximal to a breast tumor is stimulated by PGE2 via cyclic AMP, leading to activation of promoter II of the CYP19 (aromatase) gene. Endocrinology 137:5739-5742
25. Hughes R, Timmermans P, Schrey MP 1996 Regulation of arachidonic acid metabolism, aromatase activity and growth in human breast cancer cells by interleukin-1β and phorbol ester: dissociation of a mediatory role for prostaglandin E2 in the autocrine control of cell function. Int J Cancer 67:684-689
26. Harris RE, Namboodiri KK, Farrar WB 1996 Nonsteroidal antiinflammatory drugs and breast cancer. Epidemiology 7:203-205
27. Harris RE, Robertson FM, Abou-Issa HM, Farrar WB, Brueggemeier R 1999 Genetic induction and upregulation of cyclooxygenase (COX) and aromatase (CYP19): an extension of the dietary fat hypothesis of breast cancer. Med Hypotheses 52:291-292
28. Arun B, Goss P 2004 The role of COX-2 inhibition in breast cancer treatment and prevention. Semin Oncol 31:22-29
29. Terry MB, Gammon MD, Zhang FF, Tawfik H, Teitelbaum SL, Britton JA, Subbaramaiah K, Dannenberg AJ, Neugut AI 2004 Association of frequency and duration of aspirin use and hormone receptor status with breast cancer risk. JAMA 291:2433-2440
30. Brueggemeier RW, Quinn AL, Parrett ML, Joarder FS, Harris RE, Robertson FM 1999 Correlation of aromatase and cyclooxygenase gene expression in human breast cancer specimens. Cancer Lett 140:27-35
31. Brodie AM, Lu Q, Long BJ, Fulton A, Chen T, Macpherson N, Dejong PC, Blankenstein MA, Nortier JW, Slee PH, van de Ven J, van Gorp JM, Elbers JR, Schipper ME, Blijham GH, Thijssen JH 2001 Aromatase and COX-2 expression in human breast cancers. J Steroid Biochem Mol Biol 79:41-47
32. Richards JA, Brueggemeier RW 2003 Prostaglandin E2 regulates aromatase activity and expression in human adipose stromal cells via two distinct receptor subtypes. J Clin Endocrinol Metab 88:2810-2816
33. Brueggemeier RW, Diaz-Cruz ES, Li PK, Sugimoto Y, Lin YC, Shapiro CL, Translational studies on aromatase, cyclooxygenases, and enzyme inhibitors in breast cancer. J Steroid Biochem Mol Biol, in press
34. Diaz-Cruz ES, Shapiro CL, Brueggemeier RW 2005 Cyclooxygenase inhibitors suppress aromatase expression and activity in breast cancer cells. J Clin Endocrinol Metab 90:2563-2570
35. Carmichael PL 1998 Mechanisms of action of antiestrogens: relevance to clinical benefits and risks. Cancer Invest 16:604-611
36. Jordan VC 1995 Tamoxifen: toxicities and drug resistance during the treatment and prevention of breast cancer. Annu Rev Pharmacol Toxicol 35:195-211
37. Harvey HA, Lipton A, Santen RJ 1982 Aromatase: new perspectives for breast cancer. Cancer Res 42(Suppl):3261s-3467s
38. Santen RJ 1987 Aromatase conference: future perspectives. Steroids 50:1-665
39. Brodie AM, Brodie HJ, Callard G, Robinson CH, Roselli C, Santen RJ 1993 Proceedings of the Third International Aromatase Conference. J Steroid Biochem Mol Biol 44:321-696
40. Simpson ER, Bhatnagar A, Brodie AM, Brueggemeier RW, Chen S, DeCoster R, Dowsett M, Harada N, Naftolin F, Osawa Y, Plourde P, Reed MJ, Santen RJ 1997 Proceedings of the Fourth International Aromatase Conference. J Steroid Biochem Mol Biol 61:107-425
41. Simpson ER 2001 Aromatase 2000: Sixth International Aromatase Conference. J Steroid Biochem Mol Biol 79:1-314
42. Johnston JO, Metcalf BW 1984 Aromatase: a target enzyme in breast cancer. In: Sunkara P, ed. Novel approaches to cancer chemotherapy. New York: Academic Press; 307-328
43. Banting L, Smith HJ, James M, Jones G, Nazareth W, Nicholls PJ, Hewlins MJ, Rowlands MG 1988 Structure-activity relationships for non-steroidal inhibitors of aromatase. J Enzym Inhib 2:215-229
44. Banting L, Nicholls PJ, Shaw MA, Smith HJ 1989 Recent developments in aromatase inhibition as a potential treatment for oestrogen-dependent breast cancer. Prog Med Chem 26:253-298
45. Covey DF 1988 Aromatase inhibitors: specific inhibitors of oestrogen biosynthesis. In: Berg D, Plempel M, eds. Sterol biosynthesis inhibitors. Chichester, UK: Ellis Horwood; 534-571
46. Brueggemeier RW 1990 Biochemical and molecular aspects of aromatase. J Enzym Inhib 4:101-111
47. Brueggemeier RW 1994 Aromatase inhibitors - mechanisms of steroidal inhibitors. Breast Cancer Res Treat 30:31-42
48. Cole PA, Robinson CH 1990 Mechanism and inhibition of cytochrome P-450 aromatase. J Med Chem 33:2933-2942
49. Brodie AM, Njar VC 1996 Aromatase inhibitors and breast cancer. Semin Oncol 23:10-20
50. Brodie A, Lu Q, Long B 1999 Aromatase and its inhibitors. J Steroid Biochem Mol Biol 69:205-210
51. Santen RJ, Harvey HA 1999 Use of aromatase inhibitors in breast carcinoma. Endocr Relat Cancer 6:75-92
52. Schwarzel WC, Kruggel WG, Brodie HJ 1973 Studies on the mechanism of estrogen biosynthesis. 8. The development of inhibitors of the enzyme system in human placenta. Endocrinology 92:866-880
53. Siiteri PK, Thompson EA 1975 Studies of human placental aromatase. J Steroid Biochem 6:317-322
54. Brueggemeier RW, Floyd EE, Counsell RE 1978 Synthesis and biochemical evaluation of inhibitors of estrogen biosynthesis. J Med Chem 21:1007-1011
55. Henderson D, Norbisrath G, Kerb U 1986 1-Methyl-1,4-androstadiene-3,17- dione (SH 489): characterization of an irreversible inhibitor of estrogen biosynthesis. J Steroid Biochem 24:303-306
56. Brueggemeier RW, Katlic NE 1987 Effects of the aromatase inhibitor 7 α-(4′-amino)phenylthio-4-androstene-3,17-dione in MCF-7 human mammary carcinoma cell culture. Cancer Res 47:4548-4551
57. Brueggemeier RW, Katlic NE, Kenreigh CA, Li PK 1992 Aromatase inhibition by 7-substituted steroids in human choriocarcinoma cell culture. J Steroid Biochem Mol Biol 41:85-90
58. Brueggemeier RW, Li PK 1988 Effects of the aromatase inhibitor 7 α-(4′-amino)phenylthio-4-androstene-3,17-dione on 7,12-dimethylbenz(a)anthracene-induced mammary carcinoma in rats. Cancer Res 48:6808-6810
59. Li PK, Brueggemeier RW 1990 Synthesis and biochemical studies of 7-substituted 4,6-androstadiene-3,17-diones as aromatase inhibitors. J Med Chem 33:101-105
60. Kellis JT, Childers WE, Robinson CH, Vickery LE 1987 Inhibition of aromatase cytochrome P-450 by 10-oxirane and 10-thiirane substituted androgens. Implications for the structure of the active site. J Biol Chem 262:4421-4426
61. Childers WE, Shih MJ, Furth PS, Robinson CH 1987 Stereoselective inhibition of human placental aromatase. Steroids 50:121-134
62. Shih MJ, Carrell MH, Carrell HL, Wright CL, Johnston JO, Robinson CH 1987 Stereoselective inhibition of aromatase by novel epoxysteroids. J Chem Soc Chem Comm 213-214
63. Bednarski PJ, Porubek DJ, Nelson SD 1985 Thiol-containing androgens as suicide substrates of aromatase. J Med Chem 28:775-779
64. Wright JN, Calder MR, Akhtar M 1985 Steroidal C-19 sulfur and nitrogen derivatives designed as aromatase inhibitors. J Chem Soc Chem Comm 1733-1735
65. Peet NP, Burkhart JP, Wright CL, Johnston JO 1992 Time-dependent inhibition of human placental aromatase with a 2,19-methyleneoxy-bridged androstenedione. J Med Chem 35:3303-3306
66. Peet NP, Johnston JO, Burkhart JP, Wright CL 1993 A-ring bridged steroids as potent inhibitors of aromatase. J Steroid Biochem Mol Biol 44:409-420
67. Johnston JO, Wright CL, Burkhart JP, Peet NP 1993 Biological characterization of A-ring steroids. J Steroid Biochem Mol Biol 44:623-631
68. Metcalf BW, Wright CL, Burkhart JP, Johnston JO 1981 Substrate-induced inactivation of aromatase by allenic and acetylenic steroids. J Am Chem Soc 103:3221-3222
69. Covey DF, Hood WF, Parikh VD 1981 10β-Propynyl-substituted steroids. Mechanism-based enzyme-activated irreversible inhibitors of estrogen biosynthesis. J Biol Chem 256:1076-1079
70. Marcotte PA, Robinson CH 1982 Synthesis and evaluation of 10β-substituted 4-estrene-3,17-diones as inhibitors of human placental microsomal aromatase. Steroids 39:325-344
71. Johnston JO, Wright CL, Metcalf BW 1984 Biochemical and endocrine properties of a mechanism-based inhibitor of aromatase. Endocrinology 115:776-785
72. Johnston JO, Wright CL, Metcalf BW 1984 Time-dependent inhibition of aromatase in trophoblastic tumor cells in tissue culture. J Steroid Biochem 20:1221-1226
73. Longcope C, Femino A, Johnston JO 1988 Inhibition of peripheral aromatization in baboons by an enzyme-activated aromatase inhibitor (MDL 18,962). Endocrinology 122:2007-2011
74. Johnston JO 1987 Biological characterization of 10-(2-propynyl) estr-4-ene-3,17-dione (MDL 18,962), an enzyme-activated inhibitor of aromatase. Steroids 50:105-120
75. Brodie AM, Garrett 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
76. Brodie AM, Schwarzel WC, Shaikh AA, Brodie HJ 1977 The effect of an aromatase inhibitor, 4-hydroxy-4-androstene-3,17-dione, on estrogen-dependent processes in reproduction and breast cancer. Endocrinology 100:1684-1695
77. Wing LY, Garrett WM, Brodie AM 1985 Effects of aromatase inhibitors, aminoglutethimide, and 4-hydroxyandrostenedione on cyclic rats and rats with 7,12-dimethylbenz(a)anthracene-induced mammary tumors. Cancer Res 45:2425-2428
78. Brodie AM, Garrett WM, Hendrickson JR, Tsai-Morris CH 1982 Effects of aromatase inhibitor 4-hydroxyandrostenedione and other compounds in the 7,12-dimethylbenz(a)anthracene-induced breast carcinoma model. Cancer Res 42(Suppl):3360s-3364s
79. Coombes RC, Goss P, Dowsett M, Gazet JC, Brodie A 1984 4-Hydroxyandrostenedione in treatment of postmenopausal patients with advanced breast cancer. Lancet 2:1237-1239
80. Goss PE, Powles TJ, Dowsett M, Hutchison G, Brodie AM, Gazet JC, Coombes RC 1986 Treatment of advanced postmenopausal breast cancer with an aromatase inhibitor, 4-hydroxyandrostenedione: phase II report. Cancer Res 46:4823-4826
81. Dowsett M 1994 Aromatase inhibition: basic concepts, and the pharmacodynamics of formestane. Ann Oncol 5(Suppl 7):S3-S5
82. Goss PE, Jarman M, Wilkinson JR, Coombes RC 1986 Metabolism of the aromatase inhibitor 4-hydroxyandrostenedione in vivo. Identification of the glucuronide as a major urinary metabolite in patients and biliary metabolite in the rat. J Steroid Biochem 24:619-622
83. Wiseman LR, Goa KL 1996 Formestane. A review of its pharmacological properties and clinical efficacy in the treatment of post-menopausal breast cancer. Drugs Aging 9:292-306
84. Covey DF, Hood WF 1981 Enzyme-generated intermediates derived from 4-androstene-3,6,17-trione and 1,4,6-androstatriene-3,17-dione cause a time-dependent decrease in human placental aromatase activity. Endocrinology 108:1597-1599
85. Covey DF, Hood WF 1982 Aromatase enzyme catalysis is involved in the potent inhibition of estrogen biosynthesis caused by 4-ace. Mol Pharmacol 21:173-180
86. Snider CE, Brueggemeier RW 1987 Potent enzyme-activated inhibition of aromatase by a 7α-substituted C19 steroid. J Biol Chem 262:8685-8689
87. Li PK, Brueggemeier RW 1990 7-Substituted 1,4,6-androstatriene-3,17- diones as enzyme-activated irreversible inhibitors of aromatase. J Steroid Biochem 36:533-539
88. Ebrahimian S, Chen HH, Brueggemeier RW 1993 Synthesis and biochemical studies of 7α-substituted androsta-1,4-diene-3,17-diones as enzyme-activated irreversible inhibitors of aromatase. Steroids 58:414-422
89. O'Reilly JM, Brueggemeier RW 1996 7α-Arylaliphatic androsta-1,4-diene-3,17-diones as enzyme-activated irreversible inhibitors of aromatase. J Steroid Biochem Mol Biol 59:93-102
90. Giudici D, Ornati G, Briatico G, Buzzetti F, Lombardi P, Di Salle E 1988 6-Methylenandrosta-1,4-diene-3,17-dione (FCE 24304): a new irreversible aromatase inhibitor. J Steroid Biochem 30:391-394
91. Zaccheo T, Giudici D, Lombardi P, Di Salle E 1989 A new irreversible aromatase inhibitor, 6-methylenandrosta-1,4-diene-3,17-dione (FCE 24304): antitumor activity and endocrine effects in rats with DMBA-induced mammary tumors. Cancer Chemother Pharmacol 23:47-50
92. Zaccheo T, Giudici D, Di Salle E 1993 Inhibitory effect of combined treatment with the aromatase inhibitor exemestane and tamoxifen on DMBA-induced mammary tumors in rats. J Steroid Biochem Mol Biol 44:677-680
93. Di Salle E, Giudici D, Briatico G, Ornati G 1990 Novel irreversible aromatase inhibitors. Ann NY Acad Sci 595:357-367
94. Brueggemeier RW, Li PK, Chen HH, Moh PP, Katlic NE 1990 Biochemical and pharmacological development of steroidal inhibitors of aromatase. J Steroid Biochem Mol Biol 37:379-385
95. Cocconi G 1994 First generation aromatase inhibitors - aminoglutethimide and testololactone. Breast Cancer Res Treat 30:57-80
96. Hoffken K 1993 Experience with aromatase inhibitors in the treatment of advanced breast cancer. Cancer Treat Rev 19(Suppl B): 37-44
97. Trunet PF, Vreeland F, Royce C, Chaudri HA, Cooper J, Bhatnagar AS 1997 Clinical use of aromatase inhibitors in the treatment of advanced breast cancer. J Steroid Biochem Mol Biol 61:241-245
98. Furet P, Batzl C, Bhatnagar A, Francotte E, Rihs G, Lang M 1993 Aromatase inhibitors: synthesis, biological activity, and binding mode of azole-type compounds. J Med Chem 36:1393-1400
99. Vanden Bossche H, Willemsens G, Roels I, Bellens D, Moereels H, Coene MC, Le Jeune L, Lauwers W, Janssen PA 1990 R 76713 and enantiomers: selective, nonsteroidal inhibitors of the cytochrome P450-dependent oestrogen synthesis. Biochem Pharmacol 40:1707-1718
100. Wouters W, Snoeck E, De Coster R 1994 Vorozole, a specific non-steroidal aromatase inhibitor. Breast Cancer Res Treat 30:89-94
101. Plourde PV, Dyroff M, Dukes M 1994 Arimidex: a potent and selective fourth-generation aromatase inhibitor. Breast Cancer Res Treat 30:103-111
102. Bhatnagar AS, Hausler A, Schieweck K, Lang M, Bowman R 1990 Highly selective inhibition of estrogen biosynthesis by CGS 20267, a new non-steroidal aromatase inhibitor. J Steroid Biochem Mol Biol 37:1021-1027
103. 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
104. Adlercreutz H 1995 Phytoestrogens: epidemiology and a possible role in cancer protection. Environ Health Perspect 103(Suppl 7): 103-112
105. Wang C, Makela T, Hase T, Adlercreutz H, Kurzer MS 1994 Lignans and flavonoids inhibit aromatase enzyme in human preadipocytes. J Steroid Biochem Mol Biol 50:205-212
106. Kellis Jr JT, Vickery LE 1984 Inhibition of human estrogen synthetase (aromatase) by flavones. Science 225:1032-1034
107. Ibrahim AR, Abul-Hajj YJ 1990 Aromatase inhibition by flavonoids. J Steroid Biochem Mol Biol 37:257-260
108. Le Bail JC, Laroche T, Marre-Fournier F, Habrioux G 1998 Aromatase and 17β-hydroxysteroid dehydrogenase inhibition by flavonoids. Cancer Lett 133:101-106
109. Le Bail JC, Pouget C, Fagnere C, Basly JP, Chulia AJ, Habrioux G 2001 Chalcones are potent inhibitors of aromatase and 17β-hydroxysteroid dehydrogenase activities. Life Sci 68:751-761
110. Kao YC, Zhou C, Sherman M, Laughton CA, Chen S 1998 Molecular basis of the inhibition of human aromatase (estrogen synthetase) by flavone and isoflavone phytoestrogens: a site-directed mutagenesis study. Environ Health Perspect 106:85-92
111. Pouget C, Fagnere C, Basly JP, Besson AE, Champavier Y, Habrioux G, Chulia AJ 2002 Synthesis and aromatase inhibitory activity of flavanones. Pharm Res 19:286-291
112. Pouget C, Fagnere C, Basly JP, Habrioux G, Chulia AJ 2002 Design, synthesis and evaluation of 4-imidazolylflavans as new leads for aromatase inhibition. Bioorg Med Chem Lett 12:2859-2861
113. Recanatini M, Bisi A, Cavalli A, Belluti F, Gobbi S, Rampa A, Valenti P, Palzer M, Palusczak A, Hartmann RW 2001 A new class of nonsteroidal aromatase inhibitors: design and synthesis of chromone and xanthone derivatives and inhibition of the P450 enzymes aromatase and 17α-hydroxylase/C17,20-lyase. J Med Chem 44:672-680
114. Brueggemeier RW, Richards JA, Joomprabutra S, Bhat AS, Whetstone JL 2001 Molecular pharmacology of aromatase and its regulation by endogenous and exogenous agents. J Steroid Biochem Mol Biol 79:75-84
115. Hodek P, Trefil P, Stiborova M 2002 Flavonoids-potent and versatile biologically active compounds interacting with cytochromes P450. Chem Biol Interact 139:1-21
116. Kim YW, Hackett JC, Brueggemeier RW 2004 Synthesis and aromatase inhibitory activity of novel pyridine-containing isoflavones. J Med Chem 47:4032-4040
117. Lipton A, Santen RJ 1974 Proceedings: medical adrenalectomy using aminoglutethimide and dexamethasone in advanced breast cancer. Cancer 33:503-512
118. Santen RJ, Samojlik E, Lipton A, Harvey H, Ruby EB, Wells SA, Kendall J 1977 Kinetic, hormonal and clinical studies with aminoglutethimide in breast cancer. Cancer 39:2948-2958
119. Santen RJ, Manni A, Harvey H, Redmond C 1990 Endocrine treatment of breast cancer in women. Endocr Rev 11:221-265
120. Brodie AM 1994 Aromatase inhibitors in the treatment of breast cancer. J Steroid Biochem Mol Biol 49:281-287
121. Goss PE, Strasser K 2001 Aromatase inhibitors in the treatment and prevention of breast cancer. J Clin Oncol 19:881-894
122. Ingle JN 2001 Current status of adjuvant endocrine therapy for breast cancer. Clin Cancer Res 7:4392s-4396s
123. Buzdar A, Howell A 2001 Advances in aromatase inhibition: clinical efficacy and tolerability in the treatment of breast cancer. Clin Cancer Res 7:2620-2635
124. Murray R 2001 Role of anti-aromatase agents in postmenopausal advanced breast cancer. Cancer Chemother Pharmacol 48:259-265
125. Hamilton A, Volm M 2001 Nonsteroidal and steroidal aromatase inhibitors in breast cancer. Oncology (Huntingt) 15:965-972
126. Buzdar AU 2001 Endocrine therapy in the treatment of metastatic breast cancer. Semin Oncol 28:291-304
127. Geisler J, King N, Dowsett M, Ottestad L, Lundgren S, Walton P, Kormeset PO, Lonning PE 1996 Influence of anastrozole (Arimidex), a selective, non-steroidal aromatase inhibitor, on in vivo aromatization and plasma oestrogen levels in postmenopausal women with breast cancer. Br J Cancer 74:1286-1291
128. Jonat W, Howell A, Blomqvist C, Eiermann W, Winblad G, Tyrrell C, Mauriac L, Roche H, Lundgren S, Hellmund R, Azab M 1996 A randomized 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 32A:404-412
129. Buzdar AU, Jones SE, Vogel CL, Wolter J, Plourde P, Webster A 1997 A phase III trial comparing anastrozole (1 and 10 milligrams), a potent and selective aromatase inhibitor, with megestrol acetate in postmenopausal women with advanced breast carcinoma. Arimidex Study Group. Cancer 79:730-739
130. Buzdar A, Jonat W, Howell A, Jones SE, Blomqvist C, Vogel CL, Eiermann W, Wolter JM, Azab M, Webster A, Plourde PV 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. Arimidex Study Group. J Clin Oncol 14:2000-2011
131. Bonneterre J, Thurlimann B, Robertson JF, Krzakowski M, Mauriac L, Koralewski P, Vergote I, Webster A, Steinberg M, von Euler M 2000 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 18:3748-3757
132. 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
133. Bonneterre J, Buzdar A, Nabholtz JM, Robertson JF, Thurlimann B, von Euler M, Sahmoud T, Webster A, Steinberg M 2001 Anastrozole is superior to tamoxifen as first-line therapy in hormone receptor positive advanced breast carcinoma. Cancer 92:2247-2258
134. Geisler J, King N, Dowsett M, Ottestad L, Lundgren S, Walton P, Kormeset PO, Lonning PE 1996 Influence of anastrozole (Aromidex), a selective, non-steroidal aromatase inhibitor, on in vivo aromatization and plasma oestrogen levels in postmenopausal women with breast cancer. Br J Cancer 74:1286-1291
135. Bajetta E, Martinetti A, Zilembo N, Pozzi P, La Torre I, Ferrari L, Seregni E, Longarini R, Salvucci G, Bombardieri E 2002 Biological activity of anastrozole in postmenopausal patients with advanced breast cancer: effects on estrogens and bone metabolism. Ann Oncol 13:1059-1066
136. Dowsett M, Jones A, Johnston SR, Jacobs S, Trunet P, Smith IE 1995 In vivo measurement of aromatase inhibition by letrozole (CGS 20267) in postmenopausal patients with breast cancer. Clin Cancer Res 1:1511-1515
137. Dombernowsky P, Smith I, Falkson G, Leonard R, Panasci L, Bellmunt J, Bezwoda W, Gardin G, Gudgeon A, Morgan M, Fornasiero A, Hoffmann W, Michel J, Hatschek T, Tjabbes T, Chaudri HA, Hornberger U, Trunet PF 1998 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 16:453-461
138. Buzdar A, Douma J, Davidson N, Elledge R, Morgan M, Smith R, Porter L, Nabholtz J, Xiang X, Brady C 2001 Phase III, multicenter, double-blind, randomized study of letrozole, an aromatase inhibitor, for advanced breast cancer versus megestrol acetate. J Clin Oncol 19:3357-3366
139. Bajetta E, Zilembo N, Dowsett M, Guillevin L, Di Leo A, Celio L, Martinetti A, Marchiano A, Pozzi P, Stani S, Bichisao E 1999 Double-blind, randomised, multicentre endocrine trial comparing two letrozole doses, in postmenopausal breast cancer patients. Eur J Cancer 35:208-213
140. Mouridsen H, Gershanovich M, Sun Y, Perez-Carrion R, Boni C, Monnier A, Apffelstaedt J, Smith R, Sleeboom HP, Janicke F, Pluzanska A, Dank M, Becquart D, Bapsy PP, Salminen E, Snyder R, Lassus M, Verbeek JA, Staffler B, Chaudri-Ross HA, Dugan M 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
141. 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
142. Evans TR, Di Salle E, Ornati G, Lassus M, Benedetti MS, Pianezzola E, Coombes RC 1992 Phase I and endocrine study of exemestane (FCE 24304), a new aromatase inhibitor, in postmenopausal women. Cancer Res 52:5933-5939
143. Bajetta E, Zilembo N, Noberasco C, Martinetti A, Mariani L, Ferrari L, Buzzoni R, Greco M, Bartoli C, Spagnoli I, Danesini GM, Artale S, Paolini J 1997 The minimal effective exemestane dose for endocrine activity in advanced breast cancer. Eur J Cancer 33:587-591
144. Geisler J, King N, Anker G, Omati G, Di Salle E, Lonning PE, Dowsett M 1998 In vivo inhibition of aromatization by exemestane, a novel irreversible aromatase inhibitor, in postmenopausal breast cancer patients. Clin Cancer Res 4:2089-2093
145. Lonning PE, Bajetta E, Murray R, Tubiana-Hulin M, Eisenberg PD, Mickiewicz E, Celio L, Pitt P, Mita M, Aaronson NK, Fowst C, Arkhipov A, Di Salle E, Polli A, Massimini G 2000 Activity of exemestane in metastatic breast cancer after failure of nonsteroidal aromatase inhibitors: a phase II trial. J Clin Oncol 18:2234-2244
146. Lonning PE 2000 Pharmacology and clinical experience with exemestane. Expert Opin Investig Drugs 9:1897-1905
147. 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
148. Boeddinghaus IM, Dowsett M 2001 Comparative clinical pharmacology and pharmacokinetic interactions of aromatase inhibitors. J Steroid Biochem Mol Biol 79:85-91
149. Miller WR, Dixon JM 2002 Endocrine and clinical endpoints of exemestane as neoadjuvant therapy. Cancer Control 9:9-15
150. Yue W, Brodie AM 1997 Mechanisms of the actions of aromatase inhibitors 4-hydroxyandrostenedione, fadrozole, and aminoglutethimide on aromatase in JEG-3 cell culture. J Steroid Biochem Mol Biol 63:317-328
151. Soudon J 2000 Comparison of in vitro exemestane activity versus other antiaromatase agents. Clin Breast Cancer 1(Suppl 1):S68-S73
152. Miller WR, Dixon JM 2000 Antiaromatase agents: preclinical data and neoadjuvant therapy. Clin Breast Cancer 1(Suppl 1):S9-S14
153. Brodie AH, Mouridsen HT 2003 Applicability of the intratumor aromatase preclinical model to predict clinical trial results with endocrine therapy. Am J Clin Oncol 26:517-526
154. Paridaens R, Dirix L, Lohrisch C, Beex L, Nooij M, Cameron D, Biganzoli L, Cufer T, Duchateau L, Hamilton A, Lobelle JP, Piccart M 2003 Mature results of a randomized phase II multicenter study of exemestane versus tamoxifen as first-line hormone therapy for postmenopausal women with metastatic breast cancer. Ann Oncol 14:1391-1398
155. Ingle JN 2001 Aromatase inhibition and antiestrogen therapy in early breast cancer treatment and chemoprevention. Oncology (Huntingt) 15:28-34
156. Buzdar AU 2003 Advances in endocrine treatments for postmenopausal women with metastatic and early breast cancer. Oncologist 8:335-341
157. Baum M, Budzar AU, Cuzick J, Forbes J, Houghton JH, Klijn JG, Sahmoud T 2002 Anastrozole alone or in combination with tamoxifen versus tamoxifen alone for adjuvant treatment of post-menopausal women with early breast cancer: first results of the ATAC randomised trial. Lancet 359:2131-2139
158. Baum M, Buzdar A, Cuzick J, Forbes J, Houghton J, Howell A, Sahmoud T 2003 Anastrozole alone or in combination with tamoxifen versus tamoxifen alone for adjuvant treatment of post-menopausal women with early-stage breast cancer: results of the ATAC (Arimidex, Tamoxifen Alone or in Combination) trial efficacy and safety update analyses. Cancer 98:1802-1810
159. Goss PE, Ingle JN, Martino S, Robert NJ, Muss HB, Piccart MJ, Castiglione M, Tu D, Shepherd LE, Pritchard KI, Livingston RB, Davidson NE, Norton L, Perez EA, Abrams JS, Therasse P, Palmer MJ, Pater JL 2003 A randomized trial of letrozole in postmenopausal women after five years of tamoxifen therapy for early-stage breast cancer. N Engl J Med 349:1793-1802
160. Coombes RC, Hall E, Gibson LJ, Paridaens R, Jassem J, Delozier T, Jones SE, Alvarez I, Bertelli G, Ortmann O, Coates AS, Bajetta E, Dodwell D, Coleman RE, Fallowfield LJ, Mickiewicz E, Andersen J, Lonning PE, Cocconi G, Stewart A, Stuart N, Snowdon CF, Carpentieri M, Massimini G, Bliss JM 2004 A randomized trial of exemestane after two to three years of tamoxifen therapy in postmenopausal women with primary breast cancer. N Engl J Med 350:1081-1092
161. Winer EP, Hudis C, Burstein HJ, Wolff AC, Pritchard KI, Ingle JN, Chlebowski RT, Gelber R, Edge SB, Gralow J, Cobleigh MA, Mamounas EP, Goldstein LJ, Whelan TJ, Powles TJ, Bryant J, Perkins C, Perotti J, Braun S, Langer AS, Browman GP, Somerfield MR 2005 American Society of Clinical Oncology technology
162. Moon RC, Steele VE, Kelloff GJ, Thomas CF, Detrisac CJ, Mehta RG, Lubet RA 1994 Chemoprevention of MNU-induced mammary tumorigenesis by hormone response modifiers: toremifene, RU 16117, tamoxifen, aminoglutethimide and progesterone. Anticancer Res 14:889-893
163. De Coster R, Van Ginckel RF, Callens MJ, Goeminne NK, Janssens BL 1992 Antitumoral and endocrine effects of (+)-vorozole in rats bearing dimethylbenzanthracene-induced mammary tumors. Cancer Res 52:1240-1244
164. Lubet RA, Steele VE, Casebolt TL, Eto I, Kelloff GJ, Grubbs CJ 1994 Chemopreventive effects of the aromatase inhibitors vorozole (R-83842) and 4-hydroxyandrostenedione in the methylnitrosourea (MNU)-induced mammary tumor model in Sprague-Dawley rats. Carcinogenesis 15:2775-2780
165. Schieweck K, Bhatnagar AS, Batzl C, Lang M 1993 Anti-tumor and endocrine effects of non-steroidal aromatase inhibitors on estrogen-dependent rat mammary tumors. J Steroid Biochem Mol Biol 44: 633-636
166. Goss PE 2003 Breast cancer prevention - clinical trials strategies involving aromatase inhibitors. J Steroid Biochem Mol Biol 86:487-493