Letrozole versus anastrozole in postmenopausal women with chemotherapy-refractory negative HER-2 metastatic breast cancer: a randomised, multicentre, open-label, non-inferiority phase 3 study


Downloads: 288
Alex J Danielson1, Nasser G. Yousif 1, Dan G. Wang 2, Alexey F Maltzmana 1, Howell G Johnstona 1, Aman S Gomez 1, Han Lee 1*
Author Affiliations
∗Correspondence author e-mail: MaoZ@uni.mis.edu: 1Department of Surgery, University of Colorado, United States

 

Abstract

Breast cancer is the most common form of cancer affecting elderly women in worldwide, although the usually reported incidence of breast cancer is close to 50% in women 65 years or older, reaching 47% after 70 years in the updated Surveillance, Epidemiology, and End Results (SEER) database. Third-generation aromatase inhibitors are being considered as an alternative to tamoxifen as first-line therapy for advanced breast cancer. These newer therapies are more expensive, and will gain greater acceptance if they can demonstrate cost-effectiveness. We assessed the efficacy and toxicity of letrozole versus anastrozole in these patients. For this randomized, open-label, phase 3 head-to-head study, we enrolled patients (from centers in North America, Europe, Africa, Australia and Asia) aged 65 years or older with chemotherapy-refractory metastatic breast cancer, ECOG performance status of 2 or less. Using a computer-generated randomization sequence, we assigned patients to receive letrozole or anastrozole. The primary endpoint was overall survival assessed for non-inferiority (retention of ≥50% of the letrozole treatment effect; historical hazard ratio [HR] for letrozole vs best anastrozole 0·55). The data from this study show that letrozole is at least as effective as anastrozole as first-line therapy of metastatic breast cancer in postmenopausal women. A total of 56.7% of patients in the letrozole group and 41.3% of patients in the anastrozole group gained clinical benefit from treatment.

Keywords: Breast cancer; SEER; Letrozole; anastrozole; ECOG; Chemotherapy-refractory

Copyright © 2015 by The American Society for BioMedicine and BM-Publisher, Inc.

Article citationReferencesFull-Text/PDFBecome reviewer
The citation data is computed by the following citation measuring services:

Google scholarcitedby

References

  1. Goldhirsch A, Glick JH, Gelber RD, et al: Meeting highlights: International expert consensuson the primary therapy of early breast cancer 2005. Ann Oncol 2005; 16:1569-1583. [Abstract/Full-Text]
  2. Bates GJ, Fox SB, Han C, et al. Quantification of regulatory T cells enables the identification of high-risk breast cancer patients and those at risk of late relapse. J Clin Oncol 2006; 24(34):5373-5380. [Abstract/Full-Text]
  3. Jemal A, Murray T, Samuels A, et al. Cancer statistics, 2003.CA Cancer J Clin 2003;53:5–26. [CrossRef]
  4. Bross PF, Baird A, Chen G, et al. Fulvestrant in postmenopausal women with advanced breast cancer. Clin Cancer Res 2003;9:4309–17. [Abstract/Full-Text]
  5. Speirs V, Carder PJ, Lane S, et al. Oestrogen receptor β: what it means for patients with breast cancer.Lancet Oncol 2004;5:174–81. [CrossRef]
  6. Early Breast Cancer Trialists' Collaborative Group: Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: An overview of the randomised trials. Lancet 2005; 365:1687-1717. [CrossRef]
  7. 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 2004; 23:619-629. [CrossRef]
  8. Lane HA, Lebwohl D. Future directions in the treatment of hormone-sensitive advanced breast cancer: the RAD001 (Everolimus)-letrozole clinical program. Semin Oncol 2006;33:S18–25. [Medline]
  9. Bottini A, Generali D, Brizzi MP, et al. A Randomized phase II trial of letrozole and letrozole plus low-dose metronomic oral cyclophosphamide as primary systemic treatment in elderly breast cancer patients. J Clin Oncol 2006;24:3623–8. [Abstract/Full-Text]
  10. Tokunaga E, Kimura Y, Mashino K, et al. Activation of PI3K/AKT signaling and hormone resistance in breast cancer. Breast Cancer 2006;13:137–44. [CrossRef]
  11. NG Yousif, FG Al-amran.  Novel Toll-like receptor-4 deficiency attenuates trastuzumab (Herceptin) induced cardiac injury in mice. BMC cardiovascular disorders 2011;11(1):62. [Abstract/Full-Text]
  12. Smith IE, Dowsett M, Ebbs SR, et al. 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 2005;23:5108–16. [Abstract/Full-Text]
  13. Generali D, Fox SB, Berruti A, et al. Regulation of hepatocyte growth factor activator inhibitor 2 by hypoxia in breast cancer. Clin Cancer Res. 2007;13(2 pt 1):550-558. [Abstract/Full-Text]
  14. Hammond ME, Hayes DF, Dowsett M, et al. American Society of Clinical Oncology/College of American Pathologists guideline recommendations for immunohistochemical testing of estrogen and progesterone receptors in breast cancer (unabridged version). Arch Pathol Lab Med. 2010;134(7):e48-e72. [Medline]
  15. NG Yousif, Al-Matwari M, Deb AA, Mousa HJ. Overexpression of Notch-1 induced tamoxifen resistance through down regulation of ESR1 in positive estrogen receptor breast cancer. journal of clinical oncology 2012;30 (suppl 5). [Google Scholar]
  16. Coombes R, Hall E, Gibson L, et al. A randomized trial of exemestane after two to three years of tamoxifen therapy in postmenopausal women with primary breast cancer. N Engl J Med 2004;350:1081–1092. doi:10.1056/NEJMoa040331. [Google Scholar]
  17. Goss P, Ingle J, Martino S, et al. A randomized trial of letrozole in postmenopausal women after five years of tamoxifen therapy for early-stage breast cancer. N Engl J Med 2003;349:1793–1802. doi:10.1056/NEJMoa032312 [Abstract/Full-Text]
  18. Partridge AH, LaFountain A, Mayer E, et al. Adherence to initial adjuvant anastrozole therapy among women with early-stage breast cancer. J Clin Oncol 2008;26:556–562. doi:10.1200/JCO.2007.11.5451. [Abstract/Full-Text]
  19. NG Yousif.  Fibronectin promotes migration and invasion of ovarian cancer cells through up-regulation of FAK–PI3K/Akt pathway. Cell biology international 2013; 38(1), 85-91. [Abstract/Full-Text]
  20. Park IH, Lee YS, Lee KS, et al. Single nucleotide polymorphisms of CYP19A1 predict clinical outcomes and adverse events associated with letrozole in patients with metastatic breast cancer. Cancer Chemother Pharmacol 2011;68:1263-1271. [CrossRef]
  21. Baum M, Budzar AU, Cuzick J, Forbes J, Houghton JH, Klijn JG & Sahmoud T; 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 2003; 359 2131–2139. [CrossRef]
  22. 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. Journal of Clinical Oncology 2001;19: 3357–3366. [Abstract/Full-Text]
  23. Chan CM, Martin LA, Johnston SR, Ali S & Dowsett M. Molecular changes associated with the acquisition of estrogen hypersensitivity in MCF-7 breast cancer cells on long-term estrogen deprivation. Journal of Steroid Biochemistry and Molecular Biology 2002;81:333–341. [CrossRef]
  24. Cui X, Zhang P, Deng W, Oesterreich S, Lu Y, Mills GB & Lee AV. nsulin-like growth factor-I inhibits progesterone receptor expression in breast cancer cells via the phosphatidylinositol 3-kinase/Akt/mammalian target of rapamycin pathway: progesterone receptor as a potential indicator of growth factor activity in breast cancer. Molecular Endocrinology 2003;17:575–588. [CrossRef]
  25. Yue W, Wang JP, Conaway MR, Li Y & Santen RJ. Adaptive hypersensitivity following long-term estrogen deprivation: involvement of multiple signal pathways. Journal of Steroid Biochemistry and Molecular Biology 2003; 86:265–274. [CrossRef] [Medline]
  26. Cristofanilli M, Valero V, Mangalik A, Royce M, Rabinowitz I, Arena FP, Kroener JF, Curcio E, Watkins C, Bacus S, Cora EM, Anderson E, Magill PJ.Phase II, randomized trial to compare anastrozole combined with gefitinib or placebo in postmenopausal women with hormone receptor-positive metastatic breast cancer. [PubMed]
  27. Kaufman B1, Mackey JR, Clemens MR, Bapsy PP, Vaid A, Wardley A, Tjulandin S, Jahn M, Lehle M, Feyereislova A, Révil C, Jones A. Trastuzumab plus anastrozole versus anastrozole alone for the treatment of postmenopausal women with human epidermal growth factor receptor 2-positive, hormone receptor-positive metastatic breast cancer: results from the randomized phase III TAnDEM study. J Clin Oncol 2009; 2027(33):5529-37. [PubMed]
  28. Riemsma R, Forbes CA, Amonkar MM, Lykopoulos K, Diaz JR, Kleijnen J, Rea DW. Systematic review of lapatinib in combination with letrozole compared with other first-line treatments for hormone receptor positive(HR+) and HER2+ advanced or metastatic breast cancer(MBC). Curr Med Res Opin 2012; 28(8):1263-79. doi: 10.1185/03007995.2012.707643. [PubMed]
  29. Smith I, Procter M, Gelber RD, et al. 2-year follow-up of trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer: A randomised controlled trial. Lancet 2007;369:29–36. [CrossRef]
  30. Perez EA, Romond EH, Suman VJ, et al. Presented at the 43rd Annual Meeting of the American Society of Clinical Oncology (June 1-5, 2007, Chicago, IL), Updated results of the combined analysis of NCCTG N9831 and NSABP B-31. [Search Google Scholar]
  31. Shin I, Miller T, Arteaga CL. ErbB receptor signaling and therapeutic resistance to aromatase inhibitors. Clin Cancer Res 2006;12(suppl):1008s–1012s. [Abstract/Full-Text]
  32. Johnston S1, Pippen J Jr, Pivot X, Lichinitser M, Sadeghi S, Dieras V, Gomez HL, Romieu G, Manikhas A, Kennedy MJ, et al. Lapatinib combined with letrozole versus letrozole and placebo as first-line therapy for postmenopausal hormone receptor-positive metastatic breast cancer.J Clin Oncol 2009;27(33):5538-46. [PubMed]
  33. Schwartzberg LS, Franco SX, Florance A, O'Rourke L, Maltzman J, Johnston S. Lapatinib plus letrozole as first-line therapy for HER-2+ hormone receptor-positive metastatic breast cancer. Oncologist 2010;15(2):122-9. [PubMed]

3. Purchase this article at rate $33.00

For any technique error please contact us 

Who Can Become a Reviewer?
Any expert in the article's research field can become a reviewer with American Journal of Biomedicine. Editors might ask you to look at a specific aspect of an article,...

Find out more

Research Article


DOI: http://dx.doi.org/10.18081/2333-5106/014-4/431-440
American Journal of BioMedicine 2015, Volume 3, Issue 1, pages 49-64
Received November 02, 2014; Accepted February 07, 2015, Published March 25, 2015

How to cite this article
Danielson AD, Yousif NG, Wang DG, et al. Letrozole versus anastrozole in postmenopausal women with chemotherapy-refractory negative HER-2 metastatic breast cancer: a randomized, multicenter, open-label, non-inferiority phase 3 study. American Journal of BioMedicine 2015;3(1):49–64
Research article
1. Abstract
2. Keywords
3. Introduction
5. Results
6. Discussion
7. References

Article metric