Skip to main content

Advertisement

Log in

Role of aromatase inhibitors in the upfront adjuvant hormonal therapy of postmenopausal patients with breast cancer

  • Review Article
  • Published:
Indian Journal of Surgical Oncology Aims and scope Submit manuscript

Abstract

Tamoxifen has been considered for several decades as the standard upfront hormonal therapy for patients with endocrine-sensitive early breast cancer. The efficacy and favorable toxicity profiles of third-generation aromatase inhibitors (AIs), anastrozole, letrozole and exemestane, in advanced disease led to their development in early breast cancer. Recent trial results consistently showed the superiority of AIs over tamoxifen in using the two following therapeutic approaches: either the upfront strategy (randomization of newly diagnosed patients: tamoxifen for 5 years vu AI for 5 years) or the sequencial strategy (randomization of newly diagnosed patients: tamoxifen (2–3 years) followed by AI or the inverse for a total of 5 years vs upfront AI for 5 years).

Despite some common characteristics, a body of evidence on AIs suggests some specific differences between the three agents in terms of efficacy as well as toxicity profiles. Thus, these hormonal agents may not be considered interchangeable in clinical practice. This review will explore available results from AIs trials and will try to define their present role in the upfront adjuvant management of postmenopausal patients with breast cancer.

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

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Parkin DM, Bray F, Ferlay J, Pisani P Global cancer statistics, 2002. CA Cancer J Clin. 2005;55:74–108.

    Article  PubMed  Google Scholar 

  2. Early Breast Cancer Trialists’ Collaborative Group (EBCTCG). Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomised trials. Lancet. 2005;365(9472):1687–717.

    Article  Google Scholar 

  3. Andre F, Slimane K, Bachelot T, et al. Breast cancer with synchronous metastases: trends in survival during a 14-year period. J Clin Oncol. 2004;22:3302–3308.

    Article  PubMed  Google Scholar 

  4. Colozza M, Cardoso F, Sotiriou C, et al. Bringing molecular prognosis and prediction to the clinic. Clin Breast Cancer. 2005;6:61–76.

    Article  CAS  PubMed  Google Scholar 

  5. Endogenous Hormones and Breast Cancer Collaborative Group Endogenous sex hormones and breast cancer in postmenopausal women: reanalysis of nine prospective studies. J Natl Cancer Inst. 2002;94:606–616.

    Google Scholar 

  6. Allred DC, Mohsin SK, Fuqua SA. Histological and biological evolution of human premalignant breast disease. Endocr Relat Cancer. 2001;8:47–61.

    Article  CAS  PubMed  Google Scholar 

  7. Beatson G On the treatment of inoperable cases of carcinoma of the mamma: suggestions for a new method of treatment, with illustrative cases. Lancet. 1896;2:104–107.

    Article  Google Scholar 

  8. Ring A, Dowsett M. Mechanisms of tamoxifen resistance. Endocr Relat Cancer. 2004;11:643–658.

    Article  CAS  PubMed  Google Scholar 

  9. Wysowski DK, Honig S, Beitz J. Uterine sarcoma associated with tamoxifen use. N Engl J Med. 2002;346:1832–1833.

    Article  PubMed  Google Scholar 

  10. Fisher B, Dignam J, Bryant J, et al. Five versus more than five years of tamoxifen therapy for breast cancer patients with negative lymph nodes and estrogen receptor-positive tumors. J Natl Cancer Inst. 1996;88:1529–1542.

    Article  CAS  PubMed  Google Scholar 

  11. Segaloff A, Weeth JB, Meyer KK, et al. Hormonal therapy in cancer of the breast. 19. Effect of oral administration of delta-1-testolactoneon clinical course and hormonal excretion. Cancer. 1962;15:633–635.

    Article  CAS  Google Scholar 

  12. 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;18:3758–3767.

    CAS  PubMed  Google Scholar 

  13. 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;18:3748–3757.

    CAS  PubMed  Google Scholar 

  14. Bonneterre J, Buzdar A, Nabholtz JM, et al. Anastrozole is superior to tamoxifen as first-line therapy in hormone receptor positive advanced breast carcinoma. Cancer. 2001;92:2247–2258.

    Article  CAS  PubMed  Google Scholar 

  15. Nabholtz JM, Bonneterre J, Buzdar A, Robertson JF, Thurlimann B Anastrozole (Arimidex) versus tamoxifen as first-line therapy for advanced breast cancer in postmenopausal women: survival analysis and updated safety results. Eur J Cancer. 2003;39:1684–1689.

    Article  CAS  PubMed  Google Scholar 

  16. Mouridsen H, Gershanovich M, Sun Y, et al. 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. 2003;21:2101–2109.

    Article  CAS  PubMed  Google Scholar 

  17. Paridaens R, Therasse P, Dirix L, et al. First line hormonal treatment (HT) for metastatic breast cancer (MBC) with exemestane (E) or tamoxifen (T) in postmenopausal patients (pts) — A randomized phase III trial of the EORTC Breast Group. Proc ASCO 23: abs 515, 2004.

    Google Scholar 

  18. Saphner T, Tormey DC, Gray R. Annual hazard rates of recurrence for breast cancer after primary therapy. J Clin Oncol. 1996;14:2738–2746.

    CAS  PubMed  Google Scholar 

  19. 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.

    Article  Google Scholar 

  20. The ATAC Trialists’ Group. 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. 2003;98:1802–1810.

    Article  Google Scholar 

  21. ATAC Trialists’ Group. Results of the ATAC (Arimidex, Tamoxifen, Alone or in Combination) trial after completion of 5 years’ adjuvant treatment for breast cancer. Lancet. 2005;365:60–62.

    Article  Google Scholar 

  22. ATAC Trialists’ Group. Effect of anastrozole and tamoxifen as adjuvant treatment for early-stage breast cancer: 100 month analysis of the ATAC trial. http//oncololy/Thelancet.com 2005; DOI:10.1016/S1470-2045(07)70385-6.

  23. Coates A, Keshaviah A, Thurlimann B et al. 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. 2007;25(5):486–492.

    Article  CAS  PubMed  Google Scholar 

  24. Mouridsen HT, Giobbie-Hurder A, Mauriac L et al. For the BIG I-98 Collaborative and the International Breast Cancer Study Group Bern, Switzerland. A randomized double-blind phase III study evaluating letrozole and tamoxifen given in sequence as adjuvant endocrine therapy for postmenopausal women with receptor-positive breast cancer. Breast Cancer Res Treat. 2008; 69(suppl 2): 66S. Abstract 13. Oral presentation, San Antonio Breast Cancer Conference, December 2008.

    Google Scholar 

  25. Jones SE, Seynaeve C, Hasenburg C et al. Results of the first planned analysis of the TEAM (Tamoxifen Exemestane Adjuvant Multinational) prospective randomized phase III trial in hormone sensitive postmenopausal early breast cancer. Breast Cancer Res Treat. 2009; 69(suppl 2): 67S. Abstract 15. Oral presentation, San Antonio Breast Cancer Conference, December 2008.

    Google Scholar 

  26. Jakesz R, Gnant M, Greil R et al. Tamoxifen and anastrozole as a sequential strategy in postmenopausal women with hormone-responsive early breast cancer: updated data from the ABCSG trial 8. Breast Cancer Res Treat. 2009; 69(suppl 2): S67. Abstract 14. Oral presentation, San Antonio Breast Cancer Conference, December 2008.

    Google Scholar 

  27. Powles TJ, Hickish T, Kanis JA et al. Effect of tamoxifen on bone mineral density measured by dual-energy Xray absorptiometry in healthy premenopausal and postmenopausal women. J Clin Oncol. 1996;14:78–84.

    CAS  PubMed  Google Scholar 

  28. ATAC Trialists’ Group. 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. 2006;7(8):633–643.

    Article  Google Scholar 

  29. Winer EP, Hudis C, Burstein HJ et al. 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. 2005;23:619–629.

    Article  CAS  PubMed  Google Scholar 

  30. Gnant M, Jakesz R, Mlineritsch B et al. Zoledronic acid effectively counteracts cancer treatment induced bone loss (CTIBL) in premenopausal breast cancer patients receiving adjuvant endocrine treatment with goserelin plus anastrozole versus goserelin plus tamoxifen-bone density subprotocol results of a randomized multicenter trial (ABCSG-12). Breast Cancer Res Treat. 2004;88:S8.

    Google Scholar 

  31. Cella D, Fallowfield L, Barker P et al. Quality of life of postmenopausal women in the ATAC (’Arimidex’, Tamoxifen, Alone or in Combination) trial after completion of 5 years’ adjuvant treatment for early breast cancer. Breast Cancer Res Treat. 2006;100:273–284.

    Article  PubMed  Google Scholar 

  32. Gorodeski GI. Update on cardiovascular disease in post-menopausal women. Best Pract Res Clin Obstet Gynaecol. 2002;16(3):329–355.

    Article  PubMed  Google Scholar 

  33. Ewen M, Gluck S. A woman’s heart: The impact of adjuvant endocrine therapy on cardiovascular health. Cancer; Published online 20 February 2009.

  34. Rossouw JE, Anderson GL Prentice RL et al. Risks and benefits of estrogen plus progestin in healthy postmenopausal women: Principal results from the Women’s Health Initiative randomized controlled trial. JAMA. 2002;288:321–333.

    Article  CAS  PubMed  Google Scholar 

  35. Nabholtz JM, Glogorov J. Cardiovascular safety profiles of aromatase inhibitors: a comparative review. Drug Safety 2006;29(9):785–801.

    Article  CAS  PubMed  Google Scholar 

  36. Seruga B, Tannock IF. Upfront use of aromatase inhibitors as adjuvant therapy for breast cancer: The emperor has no clothes. J Clin Oncol. 2009;27(6):840–842.

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Jean-Marc Nabholtz.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Nabholtz, JM., Mouret-Reynier, MA., Durando, X. et al. Role of aromatase inhibitors in the upfront adjuvant hormonal therapy of postmenopausal patients with breast cancer. Indian J Surg Oncol 1, 19–26 (2010). https://doi.org/10.1007/s13193-010-0007-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13193-010-0007-9

Keywords

Navigation