Aromatase inhibitors: Are there differences between steroidal and nonsteroidal aromatase inhibitors and do they matter?

Oncologist

Volumn 13, Issue 8, 2008, Pages 829-837

  Miller, William R ^a,k   Bartlett, John ^a   Brodie, Angela M H ^b   Brueggemeier, Robert W ^c   Di Salle, Enrico ^d   Lønning, Per Eystein ^e   Llombart, Antonio ^f   Maass, Nicolai ^g   Maudelonde, Thierry ^h   Sasano, Hironobu ⁱ   Goss, Paul E ^j  

^a UNIVERSITY OF EDINBURGH   (United Kingdom)

^b UNIVERSITY OF MARYLAND SCHOOL OF MEDICINE   (United States)

^c OHIO STATE UNIVERSITY   (United States)

^d PFIZER INC   (United States)

^e UNIVERSITY OF BERGEN   (Norway)

^f HOSPITAL UNIVERSITARI ARNAU DE VILANOVA   (Spain)

^g UNIVERSITY OF KIEL   (Germany)

^h UNIV MONTPELLIER   (France)

ⁱ TOHOKU UNIVERSITY SCHOOL OF MEDICINE   (Japan)

^j HARVARD MEDICAL SCHOOL   (United States)

^k WESTERN GENERAL HOSPITAL   (United Kingdom)

more..

Author keywords

Anastrozole; Aromatase inhibitor; Exemestane; Letrozole; Mechanism of action

Indexed keywords

17 HYDROEXEMESTANE; AMINOGLUTETHIMIDE; ANASTROZOLE; AROMATASE; AROMATASE INHIBITOR; ESTROGEN; EXEMESTANE; FORMESTANE; LETROZOLE; MESSENGER RNA; NONSTEROIDAL AROMATASE INHIBITOR; PLACEBO; RALOXIFENE; SELECTIVE ESTROGEN RECEPTOR MODULATOR; STEROIDAL AROMATASE INHIBITOR; TAMOXIFEN; UNCLASSIFIED DRUG;

ADVANCED CANCER; ARTICLE; BONE ATROPHY; BREAST CANCER; CANCER PATIENT; CANCER RESISTANCE; CANCER SURVIVAL; CLINICAL TRIAL; COMBINATION CHEMOTHERAPY; COVALENT BOND; DISEASE DURATION; DRUG APPROVAL; DRUG BLOOD LEVEL; DRUG CLEARANCE; DRUG PROTEIN BINDING; ESTROGEN SYNTHESIS; HUMAN; MONOTHERAPY; NONHUMAN; PHENOTYPE; POSTMENOPAUSE; PRIORITY JOURNAL; TREATMENT OUTCOME;

AROMATASE INHIBITORS; BREAST NEOPLASMS; ENZYME INHIBITORS; FEMALE; HUMANS; RECEPTORS, ESTROGEN;

EID: 50649113295     PISSN: 10837159     EISSN: 1549490X     Source Type: Journal    
DOI: 10.1634/theoncologist.2008-0055     Document Type: Article

References (71)

1. Parkin DM, Bray F, Ferlay J et al. Global cancer statistics, 2002. CA Cancer J Clin 2005;55:74-108.
2. Barnes DM, Millis RR, Gillett CE et al. The interaction of oestrogen receptor status and pathological features with adjuvant treatment in relation to survival in patients with operable breast cancer: A retrospective study of 2660 patients. Endocr Relat Cancer 2004;11:85-96.
3. Huang HJ, Neven P, Drijkoningen M et al. Association between tumour characteristics and HER-2/neu by immunohistochemistry in 1362 women with primary operable breast cancer. J Clin Pathol 2005;58:611-616.
4. Arimidex® (anastrozole tablets) [full prescribing information]. Wilmington, DE: AstraZeneca Pharmaceuticals LP, 2005.
5. Femara® (letrozole tablets). East Hanover, NJ: Novartis Pharmaceuticals Corporation, 2007.
6. Aromasin® (exemestane). New York: Pharmacia&Upjohn Co, Division of Pfizer Inc., 2005.
7. Geisler J, Lønning PE. Aromatase inhibition: Translation into a successful therapeutic approach. Clin Cancer Res 2005;11:2809-2821.
8. di Salle E, Ornati G, Giudici D et al. Exemestane (FCE 24304), a new steroidal aromatase inhibitor. J Steroid Biochem Mol Biol 1992;43:137-143.
9. Johnston SR, Dowsett M. Aromatase inhibitors for breast cancer: Lessons from the laboratory. Nat Rev Cancer 2003;3:821-831.
10. Brueggemeier RW, Hackett JC, Diaz-Cruz ES. Aromatase inhibitors in the treatment of breast cancer. Endocr Rev 2005;26:331-345.
11. Cole PA, Robinson CH. Mechanism and inhibition of cytochrome P-450 aromatase. J Med Chem 1990;33:2933-2942.
12. Hong Y, Yu B, Sherman M et al. Molecular basis for the aromatization reaction and exemestane-mediated irreversible inhibition of human aromatase. Mol Endocrinol 2007;21:401-414.
13. Wang X, Chen S. Aromatase destabilizer: Novel action of exemestane, a Food and Drug Administration-approved aromatase inhibitor. Cancer Res 2006;66:10281-10286.
14. Kao YC, Okubo T, Sun XZ et al. Induction of aromatase expression by aminoglutethimide, an aromatase inhibitor that is used to treat breast cancer in postmenopausal women. Anticancer Res 1999;19:2049-2056.
15. Chen S, Zhou D, Okubo T et al. Breast tumor aromatase: Functional role and transcriptional regulation. Endocr Relat Cancer 1999;6:149-156.
16. Miller WR, Dixon JM. Local endocrine effects of aromatase inhibitors within the breast. J Steroid Biochem Mol Biol 2001;79:93-102.
17. Soudon J. Comparison of in vitro exemestane activity versus other antiaromatase agents. Clin Breast Cancer 2000;1(suppl 1):S68-S73.
18. Miller WR, O'Neill J. The importance of local synthesis of estrogen within the breast. Steroids 1987;50:537-548.
19. Lønning PE. Aminoglutethimide enzyme induction: Pharmacological and endocrinological implications. Cancer Chemother Pharmacol 1990;26:241-244.
20. Dowsett M, Goss PE, Powles TJ et al. Use of the aromatase inhibitor 4-hydroxyandrostenedione in postmenopausal breast cancer: Optimization of therapeutic dose and route. Cancer Res 1987;47:1957-1961.
21. Geisler J, Haynes B, Anker G et al. 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 2002;20:751-757.
22. Geisler J, King N, Anker G et al. In vivo inhibition of aromatization by exemestane, a novel irreversible aromatase inhibitor, in postmenopausal breast cancer patients. Clin Cancer Res 1998;4:2089-2093.
23. Dowsett M, Harris AL, Smith IE et al. Endocrine changes associated with relapse in advanced breast cancer patients on aminoglutethimide therapy. J Clin Endocrinol Metab 1984;58:99-104.
24. Bulun SE, Takayama K, Suzuki T et al. Organization of the human aromatase p450 (CYP19) gene. Semin Reprod Med 2004;22:5-9.
25. Miller WR, Anderson TJ, Evans DB et al. An integrated view of aromatase and its inhibition. J Steroid Biochem Mol Biol 2003;86:413-421.
26. Sourdaine P, Parker MG, Telford J et al. Analysis of the aromatase cytochrome P450 gene in human breast cancers. J Mol Endocrinol 1994;13:331-337.
27. Reed MJ, Owen AM, Lai LC et al. In situ oestrone synthesis in normal breast and breast tumour tissues: Effect of treatment with 4- hydroxyandrostenedione. Int J Cancer 1989;44:233-237.
28. Miller WR, Mullen P, Sourdaine P et al. Regulation of aromatase activity within the breast. J Steroid Biochem Mol Biol 1997;61:193-202.
29. Geisler J, Detre S, Berntsen H et al. Influence of neoadjuvant anastrozole (Arimidex) on intratumoral estrogen levels and proliferation markers in patients with locally advanced breast cancer. Clin Cancer Res 2001;7:1230-1236.
30. Chang C-Y, Jansen M, Sathya G et al. Aromasin and its 17-hydro metabolite manifest androgenic activity which may be responsible for its bone protective effect [abstract]. Breast Cancer Res Treat 2003;82(suppl 1):S103.
31. Ariazi EA, Leitao A, Oprea TI et al. Exemestane's 17-hydroxylated metabolite exerts biological effects as an androgen. Mol Cancer Ther 2007;6:2817-2827.
32. Traina TA, Poggesi I, Robson M et al. Pharmacokinetics and tolerability of exemestane in combination with raloxifene in postmenopausal women with a history of breast cancer. Breast Cancer Res Treat 2007 Oct 20 [Epub ahead of print].
33. Nicolás Diaz-Chico B, Germán Rodriguez F, González A et al. Androgens and androgen receptors in breast cancer. J Steroid Biochem Mol Biol 2007;105:1-15.
34. Nevinny-Stickel HB, Dederick MM, Haines CR et al. Comparative study of 6-dehydro-17alpha-methyltestosterone and testosterone propionate in human breast cancer. Cancer 1964;17:95-99.
35. Gordan GS, Halden A, Walter RM. Antitumor efficacy of 7 beta, 17 alpha-dimethyltestosterone (Calusterone) in advanced female breast cancer. Calif Med 1970;113:1-10.
36. Progress in the treatment of advanced breast cancer. Calif Med 1969;111:38-45.
37. Segaloff A, Weeth JB, Cuningham M et al. Hormonal therapy in cancer of the breast. 23. Effect of 7-alpha-methyl-19-nortestosterone acetate and testosterone propionate on clinical course and hormonal excretion. Cancer 1964;17:1248-1253.
38. Macedo LF, Guo Z, Tilghman SL et al. Role of androgens on MCF-7 breast cancer cell growth and on the inhibitory effect of letrozole. Cancer Res 2006;66:7775-7782.
39. Suzuki T, Miki Y, Moriya T et al. 5Alpha-reductase type 1 and aromatase in breast carcinoma as regulators of in situ androgen production. Int J Cancer 2007;120:285-291.
40. Miki Y, Suzuki T, Hatori M et al. Effects of aromatase inhibitors on human osteoblast and osteoblast-like cells: A possible androgenic bone protective effects induced by exemestane. Bone 2007;40:876-887.
41. Goss PE, Qi S, Cheung AM et al. Effects of the steroidal aromatase inhibitor exemestane and the nonsteroidal aromatase inhibitor letrozole on bone and lipid metabolism in ovariectomized rats. Clin Cancer Res 2004;10:5717-5723.
42. Goss PE, Qi S, Josse RG et al. The steroidal aromatase inhibitor exemestane prevents bone loss in ovariectomized rats. Bone 2004;34:384-392.
43. Coleman RE, Banks LM, Girgis SI et al. Skeletal effects of exemestane on bone-mineral density, bone biomarkers, and fracture incidence in postmenopausal women with early breast cancer participating in the Intergroup Exemestane Study (IES): A randomized controlled study. Lancet Oncol 2007;8:119-127.
44. Lønning PE, Geisler J, Krag LE et al. Effects of exemestane administered for 2 years versus placebo on bone mineral density, bone biomarkers, and plasma lipids in patients with surgically resected early breast cancer. J Clin Oncol 2005;23:5126-5137.
45. Geisler J, Lønning PE, Krag LE et al. Changes in bone and lipid metabolism in postmenopausal women with early breast cancer after terminating 2-year treatment with exemestane: A randomised, placebo-controlled study. Eur J Cancer 2006;42:2968-2975.
46. Goss PE, Hadji P, Subar M et al. Effects of steroidal and nonsteroidal aromatase inhibitors on markers of bone turnover in healthy postmenopausal women. Breast Cancer Res 2007;9:R52.
47. McCloskey E, Hannon R, Lakner G et al. Complete data from the letrozole (L), exemestane (E), and anastrozole (A) pharmacodynamic (PD) 'LEAP' trial: Direct comparison of safety parameters between aromatase inhibitors (AIs) in healthy postmenopausal women [abstract]. Presented at the 29th Annual San Antonio Breast Cancer Symposium, San Antonio, TX, December 14-17, 2006.
48. Iaffaioli RV, Formato R, Tortoriello A et al. Phase II study of sequential hormonal therapy with anastrozole/exemestane in advanced and metastatic breast cancer. Br J Cancer 2005;92:1621-1625.
49. Carlini P, Ferretti G, Di Cosimo S et al. Is there a benefit by the sequence anastrozole-formestane for postmenopausal metastatic breast cancer women? J Steroid Biochem Mol Biol 2003;86:107-109.
50. Murray R, Pitt P. Aromatase inhibition with 4-OHAndrostenedione after prior aromatase inhibition with aminoglutethimide in women with advanced breast cancer. Breast Cancer Res Treat 1995;35:249-253.
51. Thürlimann 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;33:1767-1773.
52. Lønning 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.
53. Carlini P, Frassoldati A, De Marco S et al. Formestane, a steroidal aromatase inhibitor after failure of non-steroidal aromatase inhibitors (anastrozole and letrozole): Is a clinical benefit still achievable? Ann Oncol 2001;12:1539-1543.
54. Zilembo N, Bajetta E, Bichisao E et al. The estrogen suppression after sequential treatment with formestane in advanced breast cancer patients. Biomed Pharmacother 2004;58:255-259.
55. Bertelli G, Garrone O, Merlano M et al. Sequential treatment with exemestane and non-steroidal aromatase inhibitors in advanced breast cancer. Oncology 2005;69:471-477.
56. Gennatas C, Michalaki V, Carvounis E et al. Third-line hormonal treatment with exemestane in postmenopausal patients with advanced breast cancer progressing on letrozole or anastrozole. A phase II trial conducted by the Hellenic Group of Oncology (HELGO). Tumori 2006;92:13-17.
57. Harper-Wynne C, English J, Meyer L et al. Randomized trial to compare the efficacy and toxicity of cyclophosphamide, methotrexate and 5-fluorouracil (CMF) with methotrexate mitoxantrone (MM) in advanced carcinoma of the breast. Br J Cancer 1999;81:316-322.
58. Geisler J, Johannessen DC, Anker G et al. Treatment with formestane alone and in combination with aminoglutethimide in heavily pretreated breast cancer patients: Clinical and endocrine effects. Eur J Cancer 1996;32A:789-792.
59. Gradishar W, Chia S, Piccart M et al. Fulvestrant versus exemestane following prior non-steroidal aromatase inhibitor therapy: First results from EFECT, a randomized, phase III trial in postmenopausal women with advanced breast cancer [abstract 12]. Presented at the 29th Annual San Antonio Breast Cancer Symposium, San Antonio, TX, December 14-17, 2006.
60. Chen S, Wang X, Masri S et al. Mechanistic studies of aromatase inhibitor (AI) resistance [abstract]. Presented at the 29th Annual San Antonio Breast Cancer Symposium, San Antonio, TX, December 14-17, 2006.
61. Chen S, Masri S, Wang X et al. What do we know about the mechanisms of aromatase inhibitor resistance? J Steroid Biochem Mol Biol 2006;102:232-240.
62. Long BJ, Jelovac D, Handratta V et al. Therapeutic strategies using the aromatase inhibitor letrozole and tamoxifen in a breast cancer model. J Natl Cancer Inst 2004;96:456-465.
63. Lu Q, Liu Y, Long BJ et al. The effect of combining aromatase inhibitors with antiestrogens on tumor growth in a nude mouse model for breast cancer. Breast Cancer Res Treat 1999;57:183-192.
64. Brodie A, Jelovac D, Macedo L et al. Therapeutic observations in MCF-7 aromatase xenografts. Clin Cancer Res 2005;11:884s-888s.
65. Zaccheo T, Giudici D, Di Salle E. Inhibitory effect of combined treatment with the aromatase inhibitor exemestane and tamoxifen on DMBA-induced mammary tumors in rats. J Steroid Biochem Mol Biol 1993;44:677-680.
66. Baum B, Budzar AU, Cuzick J et al.; 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;359:2131-2139.
67. Lien EA, Anker G, Lønning PE et al. Decreased serum concentrations of tamoxifen and its metabolites induced by aminoglutethimide. Cancer Res 1990;50:5851-5857.
68. Dowsett M, Cuzick J, Howell A et al. Pharmacokinetics of anastrozole and tamoxifen alone, and in combination, during adjuvant endocrine therapy for early breast cancer in postmenopausal women: A sub-protocol of the 'Arimidex and Tamoxifen Alone or in Combination' (ATAC) trial. Br J Cancer 2001;85:317-324.
69. Dowsett M, Pfister C, Johnston SR et al. Impact of tamoxifen on the pharmacokinetics and endocrine effects of the aromatase inhibitor letrozole in postmenopausal women with breast cancer. Clin Cancer Res 1999;5:2338-2343.
70. Rivera E, Valero V, Francis D et al. Pilot study evaluating the pharmacokinetics, pharmacodynamics, and safety of the combination of exemestane and tamoxifen. Clin Cancer Res 2004;10:1943-1948.
71. Hutson PR, Love RR, Havighurst TC et al. Effect of exemestane on tamoxifen pharmacokinetics in postmenopausal women treated for breast cancer. Clin Cancer Res 2005;11:8722-8727.