Skip to main content
SpringerLink
Log in

Spotlight on Trastuzumab in the Management of HER2-Positive Metastatic and Early-Stage Breast Cancer

  • Adis Spotlight
  • Published:
BioDrugs Aims and scope Submit manuscript

Abstract

Trastuzumab (Herceptin®) is a humanized monoclonal antibody used in the treatment of breast cancer that overexpresses human epidermal growth factor receptor 2 (HER2), which is associated with clinically aggressive disease and a poor prognosis.

The addition of intravenous trastuzumab to first-line chemotherapy improved the time to disease progression, objective response rate, duration of response, and overall survival in randomized, multicenter trials in women with HER2-positive metastatic breast cancer. As such, trastuzumab has become the standard of care in this setting, despite its high acquisition cost and potential for cardiac events, and is licensed for use in combination with paclitaxel (Europe and the US) or docetaxel (Europe). In addition, trastuzumab monotherapy is approved for use in patients with HER2-positive metastatic breast cancer who have previously received chemotherapy for their metastatic disease. Recent data from large phase III trials with trastuzumab in the adjuvant setting revealed significant improvements in disease-free and overall survival. Thus, trastuzumab is also rapidly becoming a standard component of adjuvant therapy for patients with HER2-positive early-stage breast cancer.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

Notes

  1. The use of trade names is for product identification purposes only and does not imply endorsement.

References

  1. Roche Products Ltd. Herceptin®: summary of product characteristics (annex 1); 2000 Aug 28 [online]. Available from URL: http://www.emea.eu.int/humandocs/PDFs/EPAR/Herceptin/H-278-PI-en.pdf [Accessed 2005 Nov 18]

  2. Carter P, Presta L, Gorman CM, et al. Humanization of an anti-p185HER2 antibody for human cancer therapy. Proc Natl Acad Sci U S A 1992 May; 89: 4285–9

    Article  PubMed  CAS  Google Scholar 

  3. Albanell J, Codony J, Rovira A, et al. Mechanism of action of anti-HER2 monoclonal antibodies: scientific update on trastuzumab and 2C4. Adv Exp Med Biol 2003; 532: 253–68

    Article  PubMed  CAS  Google Scholar 

  4. Herceptin® product monograph 2004 update. Basel: F. Hoffmann-La Roche Ltd, 20 04

  5. Mohsin SK, Weiss HL, Gutierrez MC, et al. Neoadjuvant trastuzumab induces apoptosis in primary breast cancers. J Clin Oncol 2005 Apr 10; 23(11): 2460–8

    Article  PubMed  CAS  Google Scholar 

  6. Izumi Y, Xu L, di Tomaso E, et al. Tumour biology: herceptin acts as an anti-angiogenic cocktail. Nature 2002; 416: 279–80

    Article  PubMed  CAS  Google Scholar 

  7. Baselga J, Norton L, Albanell J, et al. Recombinant humanized anti-HER2 antibody (Herceptin) enhances the antitumor activity of paclitaxel and doxorubicin against HER2/neu overexpressing human breast cancer xenografts. Cancer Res 1998; 58: 2825–31

    PubMed  CAS  Google Scholar 

  8. Pegram MD, Konecny GE, O’Callaghan C, et al. Rational combinations of trastuzumab with chemotherapeutic drugs used in the treatment of breast cancer. J Natl Cancer Inst 2004 May 19; 96(10): 739–49

    Article  PubMed  CAS  Google Scholar 

  9. Fujimoto-Ouchi K, Sekiguchi F, Tanaka Y. Antitumor activity of combinations of anti-HER-2 antibody trastuzumab and oral fluoropyrimidines capecitabine/5′-dFUrd in human breast cancer models. Cancer Chemother Pharmacol 2002 Mar; 49(3): 211–6

    Article  PubMed  CAS  Google Scholar 

  10. Baselga J, Carbonell X, Castaneda-Soto NJ, et al. Phase II study of efficacy, safety, and pharmacokinetics of trastuzumab monotherapy administered on a 3-weekly schedule. J Clin Oncol 2005 Apr 1; 23(10): 2162–71

    Article  PubMed  CAS  Google Scholar 

  11. Leyland-Jones B, Gelmon K, Ayoub JP, et al. Pharmacokinetics, safety, and efficacy of trastuzumab administered every three weeks in combination with paclitaxel. J Clin Oncol 2003 Nov 1; 21(21): 3965–71

    Article  PubMed  CAS  Google Scholar 

  12. Harris K, Washington CB, Lieberman J-F, et al. A population pharmacokinetic (PK) model for trastuzumab (Herceptin) and implications for clinical dosing [abstract no. 488]. Proc Am Soc Clin Oncol 2002; 21 Pt 1: 123a

    Google Scholar 

  13. Slamon DJ, Leyland-Jones B, Shak S, et al. Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2. N Engl J Med 2001 Mar 15; 344(11): 783–92

    Article  PubMed  CAS  Google Scholar 

  14. Burstein HJ, Harris LN, Gelman R, et al. Preoperative therapy with trastuzumab and paclitaxel followed by sequential adjuvant doxorubicin/cyclophosphamide for HER2 overexpressing stage II or III breast cancer: a pilot study. J Clin Oncol 2003 Jan; 21(1): 46–53

    Article  PubMed  CAS  Google Scholar 

  15. Vogel CL, Cobleigh MA, Tripathy D, et al. Efficacy and safety of trastuzumab as a single agent in first-line treatment of HER2-overexpressing metastatic breast cancer. J Clin Oncol 2002 Feb 1; 20(3): 719–26

    Article  PubMed  CAS  Google Scholar 

  16. Mass RD, Press MF, Anderson S, et al. Evaluation of clinical outcomes according to HER2 detection by fluorescence in situ hybridization in women with metastatic breast cancer treated with trastuzumab. Clin Breast Cancer 2005 Aug; 6(3): 240–6

    Article  PubMed  Google Scholar 

  17. Marty M, Cognetti F, Maraninchi D, et al. Randomized phase II trial of the efficacy and safety of trastuzumab combined with docetaxel in patients with human epidermal growth factor receptor 2-positive metastatic breast cancer administered as first-line treatment: the M77001 Study Group. J Clin Oncol 2005 Jul 1; 23(19): 4265–74

    Article  PubMed  CAS  Google Scholar 

  18. Xu L, Song S, Zhu J, et al. Results of a phase II trial of Herceptin® plus Xeloda® in patients with previously untreated HER2-positive metastatic breast cancer [abstract no. 3049]. Breast Cancer Res Treat 2004; 88Suppl. 1: 128–9. Plus poster presented at the 27th Annual San Antonio Breast Cancer Symposium; 2004 Dec 8–11; San Antonio (TX)

    Google Scholar 

  19. Esteva FJ, Valero V, Booser D, et al. Phase II study of weekly docetaxel and trastuzumab for patients with HER-2-overexpressing metastatic breast cancer. J Clin Oncol 2002 Apr 1; 20(7): 1800–8

    Article  PubMed  CAS  Google Scholar 

  20. Montemurro F, Choa G, Faggiuolo R, et al. Safety and activity of docetaxel and trastuzumab in HER2 overexpressing metastatic breast cancer: a pilot phase II study. Am J Clin Oncol 2003 Feb; 26(1): 95–7

    PubMed  CAS  Google Scholar 

  21. Tedesco KL, Thor AD, Johnson DH, et al. Docetaxel combined with trastuzumab is an active regimen in HER-2 3+ overexpressing and fluorescent in situ hybridization-positive metastatic breast cancer: a multi-institutional phase II trial. J Clin Oncol 2004 Mar 15; 22(6): 1071–7

    Article  PubMed  CAS  Google Scholar 

  22. Brufsky AM, Cleary D, Fuchs C, et al. First-line chemotherapy for metastatic breast cancer (MBC) with docetaxel (T), carboplatin (C), and traztuzumab (H): a phase II trial [abstract no. 71]. 39th Annual Meeting of the American Society of Clinical Oncology; 2003 May 31–Jun 3; Chicago (IL): 18

  23. Pegram MD, Pienkowski T, Northfelt DW, et al. Results of two open-label, multicenter phase II studies of docetaxel, platinum salts, and trastuzumab in HER2-positive advanced breast cancer. J Natl Cancer Inst 2004 May 19; 96(10): 759–69

    Article  PubMed  CAS  Google Scholar 

  24. Slamon D, Yeon CH, Pienkowski T, et al. Survival analysis from two open-label non-randomized phase II trials of trastuzumab combined with docetaxel and platinums (C, cisplatin or carboplatin) in women with HER2+ advanced breast cancer [abstract no. 642 plus poster]. 40th Annual Meeting of the American Society of Clinical Oncology; 2004 Jun 5–8; New Orleans (LA)

  25. Pienkowski T, Fumoleau P, Eiermann W, et al. Taxotere, cisplatin and Herceptin (TCH) in first-line HER2 positive metastatic breast cancer (MBC) patients, a phase II pilot study by the Breast Cancer International Research Group (BCIRG 101) [abstract no. 2030]. 37th Annual Meeting of the American Society of Clinical Oncology; 2001 May 12–15; San Francisco (CA)

  26. Yardley D, Greco A, Porter LL, et al. First-line treatment of HER2-positive metastatic breast cancer with trastuzumab, docetaxel and vinorelbine: results of a Minnie Pearl Cancer Research Network trial [abstract no. 146P]. Ann Oncol 2004; 15 Suppl. 3: iii39. Plus poster presented at the 29th European Society of Medical Oncology Congress; 2004 Oct 29–Nov 2; Vienna

  27. Brufsky A, Orlando M, Fox K, et al. Phase II study of gemcitabine and trastuzumab combination therapy in patients with HER2-overexpressing metastatic breast cancer: first stage results [abstract no. 3047]. Breast Cancer Res Treat 2004; 88 Suppl. 1: S128. Plus poster presented at the 27th San Antonio Breast Cancer Symposium; 2004 Dec 8–11; San Antonio (TX)

  28. Fountzilas G, Tsavdaridis D, Kalogera-Fountzila A, et al. Weekly paclitaxel as first-line chemotherapy and trastuzumab in patients with advanced breast cancer: a Hellenic Cooperative Oncology Group phase II study. Ann Oncol 2001 Nov; 12: 1545–51

    Article  PubMed  CAS  Google Scholar 

  29. Gasparini G, Morabito A, De Sio L, et al. Preliminary clinical results of a randomized phase IIb study of weekly pacltiaxel +/− trastuzumab as first-line therapy of patients with HER-2/neu positive metastatic breast cancer [abstract no. 227]. 26th Annual San Antonio Breast Cancer Symposium; 2003 Dec 3–6; San Antonio (TX) [online]. Available from URL: http://www.sabcs.org [Accessed 2003 Dec 3]

  30. John M, Hindenburg HJ, Hinke A, et al. Weekly paclitaxel plus trastuzumab in metastatic breast cancer: a multicentre German trial [abstract no. 458]. EJC Supplements 2003 Sep; 1(5): S139–40

    Google Scholar 

  31. Seidman AD, Fornier MN, Esteva FJ, et al. Weekly trastuzumab and paclitaxel therapy for metastatic breast cancer with analysis of efficacy by HER2 immunophenotype and gene amplification. J Clin Oncol 2001; 19(10): 2587–95

    PubMed  CAS  Google Scholar 

  32. Burris H, Yardley D, Jones S, et al. Phase II trial of trastuzumab followed by weekly paclitaxel/carboplatin as first-line treatment for patients with metastatic breast cancer. J Clin Oncol 2004 May 1; 22(9): 1621–9

    Article  PubMed  CAS  Google Scholar 

  33. Cortes J, Climent M, Lluch A, et al. Updated results of a phase II study (M77035) of Myocet® combined with weekly Herceptin® and paclitaxel in patients with HER2-positive locally advanced or metastatic breast cancer [abstract no. 3041]. Breast Cancer Res Treat 2004; 88 Suppl. 1: 125–6

    Google Scholar 

  34. Bianchi G, Albanell J, Eiermann W, et al. Pilot trial of trastuzumab starting with or after the doxorubicin component of a doxorubicin plus paclitaxel regimen for women with HER2-positive advanced breast cancer. Clin Cancer Res 2003 Dec 1; 9 (16 Pt 1): 5944–51

    PubMed  CAS  Google Scholar 

  35. Colomer R, Mayordomo JI, Calvo L, et al. HER2 ECD-positive metastatic breast cancer treated with gemcitabine, paclitaxel plus trastuzumab [abstract no. 3046]. Breast Cancer Res Treat 2004; 88Suppl. 1: S127–8. Plus poster presented at the 27th Annual San Antonio Breast Cancer Symposium; 2004 Dec 8–11; San Antonio (TX)

    Google Scholar 

  36. Fountzilas G, Christodoulou C, Tsavdaridis D, et al. Paclitaxel and gemcitabine, as first-line chemotherapy, combined with trastuzumab in patients with advanced breast cancer: a phase II study conducted by the Hellenic Cooperative Oncology Group (HeCOG). Cancer Invest 2004; 22(5): 655–62

    Article  PubMed  CAS  Google Scholar 

  37. Miller KD, Sisk J, Gize G, et al. Phase II study of gemcitabine, paclitaxel and trastuzumab in metastatic breast cancer: a Hoosier Oncology Group trial [abstract no. 437]. 25th Annual San Antonio Breast Cancer Symposium; 2002 Dec 12; San Antonio (TX) [online]. Available from URL: http://www.sabcs.org [Accessed 2003 Feb 10]

  38. Bayo-Calero JL, Mayordomo-Camara JI, Sanchez-Rovira P, et al. A multicenter study with trastuzumab and vinorelbine as first and 2nd line treatment in patients with Her2 positive metastatic breast cancer [abstract no. 5069]. Breast Cancer Res Treat 2004; 88Suppl. 1: 207–8

    Google Scholar 

  39. Burstein HJ, Harris LN, Marcom PK, et al. Trastuzumab and vinorelbine as first-line therapy for HER2-overexpressing metastatic breast cancer: multicenter phase II trial with clinical outcomes, analysis of serum tumor markers as predictive factors, and cardiac surveillance algorithm. J Clin Oncol 2003 Aug 1; 21(15): 2889–95

    Article  PubMed  CAS  Google Scholar 

  40. Chan A, Petruzelka L, Untch M, et al. Long term survival of vinorelbine and trastuzumab as first line therapy for HER2-positive metastatic breast cancer patients [abstract no. 587]. J Clin Oncol 2005 Jun 1; 23 (16 Suppl.): 25s. Plus poster presented at the 41st Annual Meeting of the American Society of Clinical Oncology; 2005 May 13–17; Orlando (FL)

  41. de Wit M, Becker K, Thomssen C, et al. Vinorelbine and trastuzumab as first line therapy in patients with HER2-positive metastatic breast cancer: interim analysis of a prospective, open-label, multicentre phase II trial [abstract no. 138P]. Ann Oncol 2004; 15Suppl. 3: iii37

    Google Scholar 

  42. Jahanzeb M, Mortimer JE, Yunus F, et al. Phase II trial of weekly vinorelbine and trastuzumab as first-line therapy in patients with HER2(+) metastatic breast cancer. Oncologist 2002; 7(5): 410–7

    Article  PubMed  CAS  Google Scholar 

  43. Cobleigh MA, Vogel CL, Tripathy D, et al. Multinational study of the efficacy and safety of humanized anti-HER2 monoclonal antibody in women who have HER2-overexpressing metastatic breast cancer that has progressed after chemotherapy for metastatic disease. J Clin Oncol 1999; 17(9): 2639–48

    PubMed  CAS  Google Scholar 

  44. Piccart-Gebhart MJ, Procter M, Leyland-Jones B, et al. Trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer. N Engl J Med 2005 Oct 20; 353(16): 1659–72

    Article  PubMed  CAS  Google Scholar 

  45. Romond EH, Perez EA, Bryant J, et al. Trastuzumab plus adjuvant chemotherapy for operable HER2-positive breast cancer. 1 2005 Oct 20; 353(16): 1673–84

  46. Slamon D, Eiermann W, Robert N, et al. Phase III randomized trial comparing doxorubicin and cyclophosphamide followed by docetaxel (AC-T) with doxorubicin and cyclophosphamide followed by docetaxel and trastuzumab (AC-TH) with docetaxel, carboplatin and trastuzumab (TCH) in HER2 positive early breast cancer patients: BCIRG 006 study [abstract no. 1 plus oral presentation]. 28th Annual San Antonio Breast Cancer Symposium; 2005 Dec 8–11; San Antonio (TX)

Download references

Acknowledgments

The full text article in Drugs 2006; 66 (4): 449–475 was reviewed by: N. Bangemann, Medical Center Benjamin Franklin, Free University, Berlin, Germany; E.B. Elkin, Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, USA; I.O. Ellis, Department of Histopathology, Nottingham City Hospital, Nottingham, England; G. Fountzilas, 1st Department of Internal Medicine, Oncology Section, AHEPA Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece; J. Horton, Comprehensive Breast Cancer Program, H. Lee Moffitt Cancer Center & Research Institute, Tampa, Florida, USA; B. Leyland-Jones, Department of Oncology, McGill University, Montreal, Quebec, Canada; F. Montemurro, Unit of Medical Oncology, Institute for Cancer Research and Treatment, Torino, Italy.

Author information

Authors and Affiliations

  1. Adis International Limited, 41 Centorian Drive, Private Bag 65901, Mairangi Bay, Auckland, 1311, New Zealand

    Greg L. Plosker & Susan J. Keam

Authors
  1. Greg L. Plosker
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Susan J. Keam
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Greg L. Plosker.

Additional information

This Spotlight is derived from abstract and summary text of an Adis Drug Evaluation originally published in full in Drugs 2006; 66 (4): 449–475. Reviewers of the original full text article are listed in the Acknowledgments section. The manufacturer of the agent under review was offered an opportunity to comment on the original article during the peer review process; changes based on any comments received were made on the basis of scientific and editorial merit

Rights and permissions

Reprints and permissions

About this article

Cite this article

Plosker, G.L., Keam, S.J. Spotlight on Trastuzumab in the Management of HER2-Positive Metastatic and Early-Stage Breast Cancer. BioDrugs 20, 259–262 (2006). https://doi.org/10.2165/00063030-200620040-00007

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2165/00063030-200620040-00007

Keywords

Search

Navigation