Skip to main content

Advertisement

Log in

HER2 overexpressing metastatic breast cancer

  • Published:
Current Treatment Options in Oncology Aims and scope Submit manuscript

Opinion statement

More than 40,000 women in the United States die each year from metastatic breast cancer. Elucidation of HER2 and its role in malignant transformation has helped define a subset of aggressive breast cancer that may be relatively resistant to non-anthracycline-based therapies and hormonal agents, but responds to targeted molecular therapy. Trastuzumab, an antibody against HER2, has proven effective as single agent therapy in women with HER2 overexpressed metastatic breast cancer. Moreover, in combination with chemotherapy, trastuzumab has been shown to delay disease progression and improve overall survival for women with HER2-positive advanced breast cancer. The combination of chemotherapy and trastuzumab is emerging as a standard of care in women with HER2 overexpressed metastatic breast cancer. Several combination regimens using trastuzumab with taxanes, vinca alkaloids, or platinum compounds have demonstrated efficacy in first- and second-line treatment settings. However, the development of anthracycline-based combinations has been limited by concerns of related cardiotoxicity. Newer multi-agent regimens are in development. The optimal combination, duration, and sequence of trastuzumab therapy remain unknown in patients with HER2-positive metastatic disease. The role of continuing treatment after disease progression is also unclear. Evidence from some retrospective analyses suggest HER2-positive tumors are relatively resistant to tamoxifen and perhaps more responsive to aromatase inhibitors, although such data are inconclusive. HER2 status should not be used routinely for clinical decision making regarding hormonal therapy options. Several ongoing trials are attempting to address these and other issues related to HER2 testing to select the most appropriate candidates for these emerging therapies. While many questions remain, the treatment of HER2 overexpressing metastatic breast cancer is rapidly evolving, and represents a new approach to treatment in oncology.

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

Access this article

Subscribe and save

Springer+ Basic
$34.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

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 and Recommended Reading

  1. Press MF, Pike MC, Chazin VR, et al.: Her2/neu expression in node negative breast cancer: direct tissue quantitation by computerized image analysis and association of overexpression with increased risk of recurrent disease. Cancer Res 1993, 53:4960–4970.

    PubMed  CAS  Google Scholar 

  2. Slamon DJ, Clark GM, Wong SG, et al.: Human breast cancer: correlation of relapse and survival with amplification of the HER2-2/neu oncogene. Science 1987, 235:177–182.

    Article  PubMed  CAS  Google Scholar 

  3. The Ludwig Breast Cancer Study Group: Prolonged disease free-survival after one course of perioperative adjuvant chemotherapy for node-negative breast cancer. N Engl J Med 1989, 320:491–496.

    Article  Google Scholar 

  4. The Ludwig Breast Cancer Study Group: Combination adjuvant chemotherapy for node-positive breast cancer. Inadequacy of a single perioperative cycle. N Engl J Med 1988, 319:677–683.

    Article  Google Scholar 

  5. Berns EM, Foekens JA, vanStaveren IL, et al.: Oncogene amplification and prognosis in breast cancer: relationship with systemic treatment. Gene 1995, 159:11–18.

    Article  PubMed  CAS  Google Scholar 

  6. Thor AD, Berry DA, Budman DR, et al.: ErbB-2, p53, and efficacy of adjuvant therapy in lymph nodepositive breast cancer. J Natl Cancer Inst 1998, 90:1340–1349.

    Article  Google Scholar 

  7. Petruzelca L, Pribyloba O, Vedralova J, et al.: c-erbB-2 expression as a predictor of outcome in a randomized trial comparing adjuvant CMF versus single agent epirubicin in stage I-II breast cancer patients [abstract]. In Proceedings of the American Society of Clinical Oncology, New Orleans, LA. May 20-23, 2000.

    Google Scholar 

  8. Revillion F, Hebbar M, Bonneterre J, Peyrat JP: Plasma c-erbB2 concentrations in relation to chemotherapy in breast cancer patients. Eur J Cancer 1996, 32A:231–234.

    Article  PubMed  CAS  Google Scholar 

  9. Borg A, Baldertorp B, Ferno M, et al.: ERBB2 amplification is associated with tamoxifen resistance in steroid-receptor positive breast cancer. Cancer Lett 1994, 81:137–144.

    Article  PubMed  CAS  Google Scholar 

  10. Pegram M, Hsu S, Lewis G, et al.: Inhibitory effects of combinations of HER-2/neu antibody and chemotherapeutic agents used for treatment of human breast cancers. Oncogene 1999, 18:2241–2251.

    Article  PubMed  CAS  Google Scholar 

  11. Baselga J, Tripathy D, Mendelsohn J, et al.: Phase II study of weekly intravenous recombinant humanized anti-p185HER2 monoclonal antibody in patients with HER2/neu-overexpressing metastatic breast cancer. J Clin Oncol 1996, 14:737–744.

    PubMed  CAS  Google Scholar 

  12. 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, 17:2639–2648.

    PubMed  CAS  Google Scholar 

  13. Vogel C, Cobleigh MA, Tripathy D: Efficacy and safety of Herceptin (trastuzumab, humanized anti-HER2 antibody) as a single agent in first-line treatment of HER2 overexpressing metastatic breast cancer (HER2+/MBC). Breast Cancer Res Treat 1998, 50:232. Abstract 21.

    Google Scholar 

  14. 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, 344:783–792.

    Article  PubMed  CAS  Google Scholar 

  15. Soriano A, Helfrich B, Holden S, et al.: Synergistic effects of chemotherapy (CT) and radiation (RT) and Herceptin against human non-small cell lung cancer (NSCLC) expressing the HER-2/neu receptor. In Twelfth International Conference on Monoclonal Antibodies for Cancer, San Diego, CA. October 14–16, 1999.

  16. Konecny G, Pegram MD, Beryt M, et al.: Therapeutic advantage of chemotherapy drugs in combination with Herceptin against human breast cancer cells with HER-2/neu overexpression. Breast Cancer Res Treat 1999, 57:114. Abstract #467.

    Google Scholar 

  17. Smith G: Current status of vinorelbine for breast cancer. Oncology 1995, 9:1767–1769.

    Google Scholar 

  18. Fumoleau P, Delozier T, Extra JM, et al.: Vinorelbine (Navelbine) in the treatment of breast cancer: the European experience. Semin Oncol 1995, 22(suppl 5):22–29.

    PubMed  CAS  Google Scholar 

  19. Burstein HJ, Kuter I, Campos SM, et al.: Clinical activity of trastuzumab and vinorelbine in women with HER2-overexpressing metastatic breast cancer. J Clin Oncol 2001, 19:2722–2730.

    PubMed  CAS  Google Scholar 

  20. Seidman A, Baselga J, Yao TJ, et al.: HER-2/neu over-expression and clinical taxane sensitivity: a multivariate analysis in patients with metastatic breast cancer (MBC). Proc Am Soc Clin Oncol 1996, 15:104. Abstract #80.

    Google Scholar 

  21. 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, 19:2587–2595.

    PubMed  CAS  Google Scholar 

  22. Kuzur M, Albain KS, Huntington MO, et al.: A Phase II trial of docetaxel and Herceptin in metastatic breast cancer patients overexpressing HER-2. Proc Am Soc Clin Oncol 2000:131a. Abstract #512.

    Google Scholar 

  23. Leyland-Jones B, Arnold A, Gelmon LK: A pharmokinetic study of Herceptin (Rm) administered with paclitaxel i.v. every 3 weeks [abstract]. Eur J Cancer 2000, 36(suppl 5):S53.

    Article  Google Scholar 

  24. Pestalozzi B, Brignoli S: Herceptin (Rm) (trastuzumab) in cerebrospinal fluid. Eur J Cancer 2000, 36(suppl 5):54.

    Article  Google Scholar 

  25. Leiberman G, Burchmore MJ, Fehrenbacher L, et al.: Health related quality of life (HRQL) of patients with HER-2 overexpressing metastatic breast cancer (MBC) treated with Herceptin (trastuzumab) as a single agent. Proc Am Soc Clin Oncol 1999, 18:417a. Abstract #1613.

    Google Scholar 

  26. Ouchi-Fujimoto 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 2001. In press.

  27. Pegram MD, Lipton A, Hayes DF, et al.: Phase II study of receptor-enhanced chemosensitivity using recombinant humanized anti-p185HER2/neu monoclonal antibody plus cisplatin in patients with HER2/ neu-overexpressing metastatic breast cancer refractory to chemotherapy treatment. J Clin Oncol 1998, 16:2659–2671.

    PubMed  CAS  Google Scholar 

  28. Pegram MD, Lipton A, Hayes DF, et al.: The effect of HER-2/neu overexpression on chemotherapeutic drug sensitivity in human breast and ovarian cancer cells. Oncogene 1997, 15:537–547.

    Article  PubMed  CAS  Google Scholar 

  29. Slamon D, Patel R, Northfelt R, et al.: A pilot study of Herceptin combined with taxotere and carboplatin (TCH) in metastatic breast cancer (MBC) patients overexpressing the HER2-neu proto-oncogene a pilot study of the UCLA network. Proc Am Soc Clin Oncol 2001, 20:49a. Abstract 193.

    Google Scholar 

  30. Pienkowski T, Fumoleau P, Eirmann 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). Proc Am Soc Clin Oncol 2001, 20:70b. Abstract #2030.

    Google Scholar 

  31. O'Shaughnessy J, Vukelja S, Marsland T, et al.: Gemcitabine and trastuzumab for HER-2 positive metastatic breast cancer: preliminary results of a Phase II study. San Antonio Breast Cancer Symposium, San Antonio, Texas. December 10–13, 2001.

    Google Scholar 

  32. Winer E, Batist G, Belt R, et al.: Reduced cardiotoxicity of liposome-encapsulated doxorubicin (TLC D-99) compared to free doxorubicin in first-line therapy of metastatic breast cancer in patients at increased risk for anthracycline-induced cardiac toxicity. Proc Am Soc Clin Oncol 2000, 19:84a. Abstract 323.

    Google Scholar 

  33. Theodoulou M, Campos S, Welles L: Cardiac safety and efficacy of TLC D99 (D, Myocet) and Herceptin (H) in advanced breast cancer (ABC). San Antonio Breast Cancer Symposium, San Antonio, Texas. December 10-13, 2001.

    Google Scholar 

  34. Mass R, et al.: Improved survival benefit from Herceptin (trastuzumab) and chemotherapy in patients selected by fluorescence in situ hybridization. San Antonio Breast Cancer Symposium, San Antonio, TX. December 10–13, 2001.

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Spigel, D.R., Burstein, H.J. HER2 overexpressing metastatic breast cancer. Curr. Treat. Options in Oncol. 3, 163–174 (2002). https://doi.org/10.1007/s11864-002-0062-8

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11864-002-0062-8

Keywords

Navigation