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The third-generation aromatase inhibitors: a clinical overview

  • Aman Buzdar
Part of the Milestones in Drug Therapy book series (MDT)

Abstract

In the USA, it is estimated that breast cancer will account for approximately 26% of all new cases of cancer in 2007 [1]. Although treatment has improved and death rates have declined in recent years, breast cancer still accounts for approximately 15% of all cancer-related deaths in women [1].

Keywords

Breast Cancer Postmenopausal Woman Clin Oncol Aromatase Inhibitor Advanced Breast Cancer 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. 1.
    American Cancer Society (2005) Cancer facts and Figures 2007 http://www.cancer.org/docroot/STT/content/STT_1x_Cancer_Facts__Figures_2007.asp
  2. 2.
    Early Breast Cancer Trialists’ Collaborative Group (1998) Tamoxifen for early breast cancer: an overview of the randomised trials. Lancet 351: 1451–1467CrossRefGoogle Scholar
  3. 3.
    Wysowski DK, Honig S, Beitz J (2002) Uterine sarcoma associated with tamoxifen use. N Engl J Med 346: 1832–1833PubMedCrossRefGoogle Scholar
  4. 4.
    Fisher B, Dignam J, Bryant J, DeCillis A, Wickerham DL, Wolmark N, Costantino J, Redmond C, Fisher ER, Bowman DM, Deschenes L et al. (1996) Five versus more than five years of tamoxifen therapy for breast cancer patients with negative lymph nodes and estrogen receptor-positive tumours. J Natl Cancer Inst 88: 1529–1542PubMedCrossRefGoogle Scholar
  5. 5.
    Santen RJ, Worgul TJ, Lipton A, Harvey H, Boucher A, Samojlik E, Wells SA (1982) Aminoglutethimide as treatment of postmenopausal women with advanced breast carcinoma. Ann Intern Med 96: 94–101PubMedGoogle Scholar
  6. 6.
    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: 4823–4826PubMedGoogle Scholar
  7. 7.
    Winer EP, Hudis C, Burstein HJ, Wolff AC, Pritchard KI, Ingle JN, Chlebowski RT, Gelber R, Edge SB, Gralow J et al. (2005) American Society of Clinical Oncology technology assessment on the use of aromatase inhibitors as adjuvant therapy for postmenopausal women with hormone receptor-positive breast cancer: status report 2004. J Clin Oncol 23: 619–629PubMedCrossRefGoogle Scholar
  8. 8.
    Buzdar A, Robertson JFR, Eiermann W, Nabholtz JM (2002) An overview of the pharmacology and pharmacokinetics of the newer generation aromatase inhibitors anastrozole, letrozole and exemestane. Cancer 95: 2006–2016PubMedCrossRefGoogle Scholar
  9. 9.
    Wasan KM, Goss PE, Pritchard PH, Shepherd L, Palmer MJ, Liu S, Tu D, Ingle JN, Heath M, Deangelis D, Perez EA (2005) The influence of letrozole on serum lipid concentrations in postmenopausal women with primary breast cancer who have completed 5 years of adjuvant tamoxifen (NCIC CTG MA.17L). Ann Oncol 16: 707–715PubMedCrossRefGoogle Scholar
  10. 10.
    Atalay G, Dirix L, Biganzoli L, Beex L, Nooij M, Cameron D, Lohrisch C, Cufer T, Lobelle JP, Mattiaci MR et al. (2004) The effect of exemestane on serum lipid profile in postmenopausal women with metastatic breast cancer: a companion study to EORTC Trial 10951, ‘Randomized phase II study in first line hormonal treatment for metastatic breast cancer with exemestane or tamoxifen in postmenopausal patients’. Ann Oncol 15: 211–217PubMedCrossRefGoogle Scholar
  11. 11.
    McCloskey E, Hannon R, Lakner G, Clack G, Miyamoto A, Eastell R (2006) The letrozole (L), exemestane (E), and anastrozole (A) pharmacodynamics (LEAP) trial: a direct comparison of bone biochemical measurements between aromatase inhibitors (AIs) in healthy postmenopausal women. J Clin Oncol (Meeting Abstracts) 24: abs 555Google Scholar
  12. 12.
    Geisler J, Haynes B, Anker G, Dowsett M, Lønning 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: 751–757PubMedCrossRefGoogle Scholar
  13. 13.
    Sainsbury R (2004) Aromatase inhibition in the treatment of advanced breast cancer: is there a relationship between potency and clinical efficacy? Br J Cancer 90: 1733–1739PubMedGoogle Scholar
  14. 14.
    Buzdar AU, Jonat W, Howell A, Jones SE, Blomqvist CP, Vogel CL, Eiermann W, Wolter JM, Steinberg M, Webster A, Lee D (1998) 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 83: 1142–1152PubMedCrossRefGoogle Scholar
  15. 15.
    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: 730–739PubMedCrossRefGoogle Scholar
  16. 16.
    Jonat W, Howell A, Blomqvist C, Eiermann W, Winblad G, Tyrrell C, Mauriac L, Roche H, Lundgren S, Hellmund R, Azab M (1996) 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 32A: 404–412PubMedCrossRefGoogle Scholar
  17. 17.
    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: 3357–3366PubMedGoogle Scholar
  18. 18.
    Dombernowsky P, Smith I, Falkson G, Leonard R, Panasci L, Bellmunt J, Bezwoda W, Gardin G, Gudgeon A, Morgan M et al. (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: 453–461PubMedGoogle Scholar
  19. 19.
    Kaufmann M, Bajetta E, Dirix LY, Fein LE, Jones SE, Zilembo N, Dugardyn JL, Nasurdi C, Mennel RG, Cervek J et al. (2000) 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 18: 1399–1411PubMedGoogle Scholar
  20. 20.
    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: 2000–2011PubMedGoogle Scholar
  21. 21.
    Rose C, Vtoraya O, Pluzanska A, Davidson N, Gershanovich M, Thomas R, Johnson S, Caicedo JJ, Gervasio H, Manikhas G et al. (2003) An open randomised trial of second-line endocrine therapy in advanced breast cancer: comparison of the aromatase inhibitors letrozole and anastrozole. Eur J Cancer 39: 2318–2327PubMedCrossRefGoogle Scholar
  22. 22.
    Bonneterre J, Buzdar A, Nabholtz JM, Robertson JF, Thürlimann B, von Euler M, Sahmoud T, Webster A, Steinberg M, Arimidex Writing Committee, Investigators Committee Members (2001) Anastrozole is superior to tamoxifen as first-line therapy in hormone receptor positive advanced breast carcinoma. Cancer 92: 2247–2258PubMedCrossRefGoogle Scholar
  23. 23.
    Bonneterre J, Thürlimann 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: 3748–3757PubMedGoogle Scholar
  24. 24.
    Nabholtz JM, Bonneterre J, Buzdar A, Robertson JFR, Thürlimann B, for the Arimidex Writing Committee on behalf of the Investigators (2003) Anastrozole (Arimidex™) versus tamoxifen as first-line therapy for advanced breast cancer in postmenopausal women: survival analysis and updated safety results. Eur J Cancer 39: 1684–1689PubMedCrossRefGoogle Scholar
  25. 25.
    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: 3758–3767PubMedGoogle Scholar
  26. 26.
    Milla-Santos A, Milla L, Portella J, Rallo L, Pons M, Rodes E, Casanovas J, Puig-Gali M (2003) Anastrozole versus tamoxifen as first-line therapy in postmenopausal patients with hormone-dependent advanced breast cancer: a prospective, randomized, phase III study. Am J Clin Oncol 26: 317–322PubMedCrossRefGoogle Scholar
  27. 27.
    Mouridsen H, Gershanovich M, Sun Y, Perez-Carrion R, Boni C, Monnier A, Apffelstaedt J, Smith R, Sleeboom HP, Jaenicke F et al. (2003) Phase III study of letrozole versus tamoxifen as first-line therapy of advanced breast cancer in postmenopausal women: analysis of survival and update of efficacy from the International Letrozole Breast Cancer Group. J Clin Oncol 21: 2101–2109PubMedCrossRefGoogle Scholar
  28. 28.
    Mouridsen H, Gershanovich M, Sun Y, Perez-Carrion R, Boni C, Monnier A, Apffelstaedt J, Smith R, Sleeboom HP, Janicke F et al. (2001) Superior efficacy of letrozole versus tamoxifen as first-line therapy for postmenopausal women with advanced breast cancer: results of a phase III study of the International Letrozole Breast Cancer Group. J Clin Oncol 19: 2596–2606PubMedGoogle Scholar
  29. 29.
    Paridaens R (2004) Final results of a randomized Phase III trial comparing exemestane with tamoxifen as first-line hormone therapy for postmenopausal women with metastatic breast cancer. http://www.asco.org/ac/1,1003,_12-002511-00_18-0026-00_19-009893,00.asp
  30. 30.
    ATAC Trialists’ Group (2005) Results of the ATAC (Arimidex, Tamoxifen, Alone or in Combination) trial after completion of 5 years’ adjuvant treatment for breast cancer. Lancet 365: 60–62CrossRefGoogle Scholar
  31. 31.
    Coates AS, Keshaviah A, Thürlimann B, Mouridsen H, Mauriac L, Forbes JF, Paridaens R, Castiglione-Gertsch M, Gelber RD, Colleoni M et al. (2007) Five years of letrozole compared with tamoxifen as initial adjuvant therapy for postmenopausal women with endocrine-responsive early breast cancer: update of study BIG 1–98. J Clin Oncol 25: 486–492PubMedCrossRefGoogle Scholar
  32. 32.
    Jones SE (2006) Exemestane as adjuvant treatment of early breast cancer: intergroup exemestane study/tamoxifen exemestane adjuvant multicenter trials. Clin Breast Cancer 6Suppl 2: S41–S44PubMedCrossRefGoogle Scholar
  33. 33.
    ATAC Trialists’ Group (2002) Anastrozole alone or in combination with tamoxifen versus tamoxifen alone for adjuvant treatment of postmenopausal women with early breast cancer: first results of the ATAC randomised trial. Lancet 359: 2131–2139CrossRefGoogle Scholar
  34. 34.
    ATAC Trialists’ Group (2003) Anastrozole alone or in combination with tamoxifen versus tamoxifen alone for adjuvant treatment of postmenopausal women with early-stage breast cancer. Results of the ATAC (Arimidex, Tamoxifen, Alone or in Combination) trial efficacy and safety update analyses. Cancer 98: 1802–1810CrossRefGoogle Scholar
  35. 35.
    Coombes RC, Kilburn LS, Snowdon CF, Paridaens R, Coleman RE, Jones SE, Jassem J, van de Velde CJ, Delozier T, Alvarez I et al. (2007) Survival and safety of exemestane versus tamoxifen after 2–3 years’ tamoxifen treatment (Intergroup Exemestane Study): a randomised controlled trial. Lancet 369: 559–570PubMedCrossRefGoogle Scholar
  36. 36.
    Jakesz R, Jonat W, Gnant M, Mittlboeck M, Greil R, Tausch C, Hilfrich J, Kwasny W, Menzel C, Samonigg H et al. (2005) Switching of postmenopausal women with endocrine-responsive early breast cancer to anastrozole after 2 years’ adjuvant tamoxifen: combined results of ABCSG trial 8 and ARNO 95 trial. Lancet 366: 455–462PubMedCrossRefGoogle Scholar
  37. 37.
    Boccardo F, Rubagotti A, Guglielmini P, Fini A, Paladini G, Mesiti M, Rinaldini M, Scali S, Porpiglia M, Benedetto C et al. (2006) Switching to anastrozole versus continued tamoxifen treatment of early breast cancer. Updated results of the Italian tamoxifen anastrozole (ITA) trial. Ann Oncol 17Suppl 7: vii10–vii14PubMedCrossRefGoogle Scholar
  38. 38.
    Jonat W, Gnant M, Boccardo F, Kaufmann M, Rubagotti A, Jakesz R (2005) Switching from adjuvant tamoxifen to anastrozole in postmenopausal women with hormone-responsive early breast cancer: a meta-analysis of the ARNO 95 trial, ABCSG Trial 8, and the ITA trial. Breast Cancer Res Treat 93: S11CrossRefGoogle Scholar
  39. 39.
    Kaufmann M, Jonat W, Hilfrich J, Eidtmann H, Gademann G, Zuna I, von Minckwitz G (2007) Improved overall survival in postmenopausal women with early breast cancer after anastrozole initiated after 2 years of treatment with tamoxifen compared with continued tamoxifen: the ARNO 95 study. J Clin Oncol 1;25(19): 2664–2670PubMedCrossRefGoogle Scholar
  40. 40.
    Saphner T, Tormey DC, Gray R (1996) Annual hazard rates of recurrence for breast cancer after primary therapy. J Clin Oncol 14: 2738–2746PubMedGoogle Scholar
  41. 41.
    Fisher B, Dignam J, Bryant J, Wolmark N (2001) Five versus more than five years of tamoxifen for lymph node-negative breast cancer: updated findings from the National Surgical Adjuvant Breast and Bowel Project B-14 randomized trial. J Natl Cancer Inst 93: 684–690PubMedCrossRefGoogle Scholar
  42. 42.
    Goss PE, Ingle JN, Martino S, Robert NJ, Muss HB, Piccart MJ, Castiglione M, Tu D, Shepherd LE, Pritchard KI et al. (2005) Randomized trial of letrozole following tamoxifen as extended adjuvant therapy in receptor-positive breast cancer: updated findings from NCIC CTG MA.17. J Natl Cancer Inst 97: 1262–1271PubMedCrossRefGoogle Scholar
  43. 43.
    Cataliotti L, Buzdar A, Noguchi S, Bines J (2004) Efficacy of pre-operative Arimidex (anastrozole) compared with tamoxifen (PROACT) as neoadjuvant therapy in postmenopausal women with hormone receptor-positive breast cancer. Eur J Cancer Suppl 2: 69, abs 46Google Scholar
  44. 44.
    Smith IE, Dowsett M, Ebbs SR, Dixon JM, Skene A, Blohmer JU, Ashley SE, Francis S, Boeddinghaus I, Walsh G (2005) Neoadjuvant treatment of postmenopausal breast cancer with anastrozole, tamoxifen, or both in combination: the immediate preoperative anastrozole, tamoxifen, or combined with tamoxifen (IMPACT) multicenter double-blind randomized trial. J Clin Oncol 23(22): 5108–5116PubMedCrossRefGoogle Scholar
  45. 45.
    Smith I, Cataliotti L (2004) Anastrozole versus tamoxifen as neoadjuvant therapy for oestrogen receptor-positive breast cancer in postmenopausal women: the IMPACT and PROACT trials. Eur J Cancer Suppl 2: 69, abs 47Google Scholar
  46. 46.
    Eiermann W, Paepke S, Appfelstaedt J, Llombart-Cussac A, Eremin J, Vinholes J, Mauriac L, Ellis M, Lassus M, Chaudri-Ross HA et al. Letrozole Neo-Adjuvant Breast Cancer Study Group (2001) Preoperative treatment of postmenopausal breast cancer patients with letrozole: a randomized double-blind multicenter study. Ann Oncol 12: 1527–1532PubMedCrossRefGoogle Scholar
  47. 47.
    Cuzick J, Powles T, Veronesi U, Forbes J, Edwards R, Ashley S, Boyle P (2003) Overview of the main outcomes in breast-cancer prevention trials. Lancet 361: 296–300PubMedCrossRefGoogle Scholar
  48. 48.
    The ATAC Trialists’ Group (2006) Comprehensive side-effect profile of anastrozole and tamoxifen as adjuvant treatment for early-stage breast cancer: long-term safety analysis of the ATAC trial. Lancet Oncol 7: 633–643CrossRefGoogle Scholar
  49. 49.
    Hillner BE, Ingle JN, Chlebowski RT, Gralow J, Yee GC, Janjan NA, Cauley JA, Blumenstein BA, Albain KS, Lipton A, Brown S (2003) American Society of Clinical Oncology 2003 update on the role of bisphosphonates and bone health issues in women with breast cancer. J Clin Oncol 21: 4042–4057PubMedCrossRefGoogle Scholar
  50. 50.
    Van Poznak C, Hannon RA, Clack G, Campone M, Mackey J, Apffelstaedt J, Eastell R, on behalf of the SABRE investigators (2006) The SABRE study: effects of risedronate on bone mineral density and bone metabolism in postmenopausal women using anastrozole as adjuvant therapy for hormone receptor-positive early breast cancer — first results. Breast Cancer Research and Treatment vol 100(Suppl 1), abs 4061Google Scholar
  51. 51.
    Howell A (2005) ATAC Trial Update. Lancet 365: 1225–1230CrossRefGoogle Scholar

Copyright information

© Birkhäuser Verlag/Switzerland 2008

Authors and Affiliations

  • Aman Buzdar
    • 1
  1. 1.Department of Breast Medical OncologyThe University of Texas M.D. Anderson Cancer CenterHoustonUSA

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