• Edith A. Perez
  • Frances M. Palmieri
  • Shelly M. Brock
Part of the Cancer Treatment and Research book series (CTAR, volume 151)

Systemic adjuvant therapy is regularly recommended for patients diagnosed with invasive breast cancer based on risk of recurrence and likelihood of benefit from therapy. Progress in molecular biology has resulted in the identification and improved understanding of molecular markers that may have prognostic and predictive value for patients with breast cancer. HER2 (human epidermal growth factor receptor 2) is one of the best characterized of these markers and now plays a critical role in patient management.


Overall Survival Left Ventricular Ejection Fraction Human Epidermal Growth Factor Receptor National Comprehensive Cancer Network National Comprehensive Cancer Network 
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.



Funding partially provided by the Breast Cancer Research Foundation.


  1. 1.
    Owens MA, Horten BC, Da Silva MM. HER2 amplification ratios by fluorescence in situ hybridization and correlation with immunohistochemistry in a cohort of 6556 breast cancer tissues. Clin Breast Cancer. 2004;5(1):63–9.PubMedCrossRefGoogle Scholar
  2. 2.
    Slamon DJ, Clark GM, Wong SG, Levin WJ, Ullrich A, McGuire WL. Human breast cancer: Correlation of relapse and survival with amplification of the HER-2/neu oncogene. Science. 1987;235(4785):177–82.PubMedCrossRefGoogle Scholar
  3. 3.
    Slamon DJ, Godolphin W, Jones LA et al. Studies of the HER-2/neu proto-oncogene in human breast and ovarian cancer. Science. 1989;244(4905):707–12.PubMedCrossRefGoogle Scholar
  4. 4.
    Yaziji H, Goldstein LC, Barry TS, et al. HER-2 testing in breast cancer using parallel tissue-based methods. JAMA. 2004;291(16):1972–7.PubMedCrossRefGoogle Scholar
  5. 5.
    Wolff AC, Hammond ME, Schwartz JN, et al. American Society of Clinical Oncology/College of American Pathologists guideline recommendations for human epidermal growth factor receptor 2 testing in breast cancer. J Clin Oncol. 2007;25(1):118–45.PubMedCrossRefGoogle Scholar
  6. 6.
    Paik S, Hazan R, Fisher ER, et al. Pathologic findings from the National Surgical Adjuvant Breast and Bowel Project: Prognostic significance of erbB-2 protein overexpression in primary breast cancer. J Clin Oncol. 1990;8(1):103–12.PubMedGoogle Scholar
  7. 7.
    Muss HB, Thor AD, Berry DA, et al. c-erbB-2 expression and response to adjuvant therapy in women with node-positive early breast cancer. N Engl J Med. 1994;330(18):1260–6.PubMedCrossRefGoogle Scholar
  8. 8.
    Paik S, Bryant J, Park C, et al. erbB-2 and response to doxorubicin in patients with axillary lymph node-positive, hormone receptor-negative breast cancer. J Natl Cancer Inst. 1998;90(18):1361–70.PubMedCrossRefGoogle Scholar
  9. 9.
    Thomas E, Berner G. Prognostic and predictive implications of HER2 status for breast cancer patients. Eur J Oncol Nursing. 2000;4(Suppl1):10–7.CrossRefGoogle Scholar
  10. 10.
    Petit AM, Rak J, Hung MC, et al. Neutralizing antibodies against epidermal growth factor and ErbB-2/neu receptor tyrosine kinases down-regulate vascular endothelial growth factor production by tumor cells in vitro and in vivo: angiogenic implications for signal transduction therapy of solid tumors. Am J Pathol. 1997;151(6):1523–30.PubMedGoogle Scholar
  11. 11.
    Baselga J, Albanell J, Molina MA, Arribas J. Mechanism of action of trastuzumab and scientific update. Semin Oncol. 2001;28(5 Suppl 16):4–11.PubMedCrossRefGoogle Scholar
  12. 12.
    Albanell J, Codony J, Rovira A, Mellado B, Gascon P. Mechanism of action of anti-HER2 monoclonal antibodies: Scientific update on trastuzumab and 2C4. Adv Exp Med Biol. 2003;532:253–68.PubMedCrossRefGoogle Scholar
  13. 13.
    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: Results of a randomized phase II trial by the M77001 Study Group. J Clin Oncol. 2005;23(19):4265–74.PubMedCrossRefGoogle Scholar
  14. 14.
    Marty M, Cognetti F, Maraninchi D, et al. Superior long-term survival benefits of trastuzumab plus docetaxel compared to docetaxel alone in patients with HER2-positive metastatic breast cancer: Patients surviving more than 4 years in the M77001 study. Breast Cancer Res Treat. 2006;100(Suppl 1):S103.CrossRefGoogle Scholar
  15. 15.
    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(11):783–92.PubMedCrossRefGoogle Scholar
  16. 16.
    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;23(10):2162–71.PubMedCrossRefGoogle Scholar
  17. 17.
    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.PubMedGoogle Scholar
  18. 18.
    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;20(3):719–26.PubMedCrossRefGoogle Scholar
  19. 19.
    Seidman A, Hudis C, Pierri MK, et al. Cardiac dysfunction in the trastuzumab clinical trials experience. J Clin Oncol. 2002;20(5):1215–21.PubMedCrossRefGoogle Scholar
  20. 20.
    Romond EH, Perez EA, Bryant J, et al. Trastuzumab plus adjuvant chemotherapy for operable HER2-positive breast cancer. N Engl J Med. 2005;353(16):1673–84.PubMedCrossRefGoogle Scholar
  21. 21.
    Piccart-Gebhart MJ, Procter M, Leyland-Jones B, et al. Trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer. N Engl J Med. 2005;353(16):1659–72.PubMedCrossRefGoogle Scholar
  22. 22.
    Perez EA, Romond EH, Suman VJ, et al. Updated results of the combined analysis of NCCTG N9831 and NSABP B-31 adjuvant chemotherapy with/without trastuzumab in patients with HER2-positive breast cancer. J Clin Oncol. 2007;25(18S):6S.Google Scholar
  23. 23.
    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(9555):29–36.PubMedCrossRefGoogle Scholar
  24. 24.
    Slamon D, Eiermann W, Robert N, et al. Phase III randomized trial comparing doxorubicin and cyclophosphamide followed by docetaxel with doxorubicin and cyclophosphamide followed by docetaxel and trastuzumab with docetaxel, carboplatin and trastuzumab in HER2-positive early breast cancer patients: BCIRG 006 study. Breast Cancer Res Treat. 2005;94(Suppl 1):S5.Google Scholar
  25. 25.
    Clinical Trials website. Maintained by the United States National Institutes of Health: National Library of Medicine. National Library of Medicine. 2007. Available at Accessed October 2007.
  26. 26.
    Pegram MD, Konecny GE, O'Callaghan C, Beryt M, Pietras R, Slamon DJ. Rational combinations of trastuzumab with chemotherapeutic drugs used in the treatment of breast cancer. J Natl Cancer Inst. 2004;96(10):739–49.PubMedCrossRefGoogle Scholar
  27. 27.
    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;96(10):759–69.PubMedCrossRefGoogle Scholar
  28. 28.
    Perez EA, Suman VJ, Rowland KM. Two concurrent phase II trials of paclitaxel/carboplatin/trastuzumab (weekly or every-3-week schedule) as first-line therapy in women with HER2-overexpressing metastatic breast cancer: NCCTG study 983252. Clin Breast Cancer. 2005;6:425–32.PubMedCrossRefGoogle Scholar
  29. 29.
    Robert N, Loesch D, Lindquist D. A randomized, phase II trial of weekly paclitaxel vs. weekly paclitaxel + carboplatin for first-line metastatic breast cancer. Breast Cancer Res Treat. 2003;77:534.Google Scholar
  30. 30.
    Robert N, Leyland-Jones B, Asmar L, et al. Randomised phase III study of trastuzumab, paclitaxel, and carboplatin versus trastuzumab and paclitaxel in women with HER-2 overexpressing metastatic breast cancer: An update including survival. Proc Am Soc Clin Oncol. 2004;23:20.Google Scholar
  31. 31.
    Rowland KM, Suman VJ, Ingle JN, et al. NCCTG 98-32-52: Randomized phase II trial of weekly versus every 3-week administration of paclitaxel, Carboplatin and trastuzumab in women with HER2 positive metastatic breast cancer (MBC). Proc Am Soc Clin Oncol 2003;22:8.Google Scholar
  32. 32.
    Perez EA, Suman VJ, Davidson NE, et al. Cardiac safety analysis of doxorubicin and cyclophosphamide followed by paclitaxel with or without wrastuzumab in the North Central Cancer Treatment Group N9831 adjuvant breast cancer trial. J Clin Oncol. 2008;26(8):1231–38.Google Scholar
  33. 33.
    Rastogi P, Jeong J, Geyer, et al. CE. Five year update of cardiac dysfunction on NSABP B-31, a randomized trial of sequential doxorubicin/cyclophosphamide (AC)→paclitaxel (T) vs. AC→T with trastuzumab (H). J Clin Oncol. 2007;25(18S):513.Google Scholar
  34. 34.
    Tan-Chiu E, Yothers G, Romond E, et al. Assessment of cardiac dysfunction in a randomized trial comparing doxorubicin and cyclophosphamide followed by paclitaxel, with or without trastuzumab as adjuvant therapy in node-positive, human epidermal growth factor receptor 2-overexpressing breast cancer: NSABP B-31. J Clin Oncol. 2005;23(31):7811–9.PubMedCrossRefGoogle Scholar
  35. 35.
    Perez EA, Suman VJ, Davidson NE, et al. Interim cardiac safety analysis of NCCTG N9831 Intergroup adjuvant trastuzumab trial. J Clin Oncol, 2005 ASCO Annual Meeting Proceedings Part I of II. Vol 23, No. 16S (June 1 Suppl), 2005:556.Google Scholar
  36. 36.
    Slamon D, Eiermann W, Robert N. Phase III trial comparing AC-T with AC-TH and with TCH in the adjuvant treatment of HER2-positive early breast cancer patients: Second interim efficacy analysis. Breast Cancer Res Treat. 2006;100(Suppl 1):52.Google Scholar
  37. 37.
    Halyard MY, Pisansky TM, Solin LJ, et al. Adjuvant radiotherapy and trastuzumab in stage I–IIA breast cancer: Toxicity data from North Central Cancer Treatment Group Phase III trial N9831. J Clin Oncol. 2006;24(18S):8S.Google Scholar
  38. 38.
    Joensuu H, Kellokumpu-Lehtinen PL, Bono P, et al. Adjuvant docetaxel or vinorelbine with or without trastuzumab for breast cancer. N Engl J Med. 2006;354(8):809–20.PubMedCrossRefGoogle Scholar
  39. 39.
    Sledge GW, O'Neill A, Thor AD. Adjuvant trastuzumab: Long-term results of E2198. Breast Cancer Res Treat. 2006;100(Suppl 1):S106.Google Scholar
  40. 40.
    NCCN Clinical Practice Guidelines in Oncology: Breast cancer. National Comprehensive Cancer Network 2007. Available at Accessed May 2007.
  41. 41.
    Chorn N. Accurate identification of HER2-positive patients is essential for superior outcomes with trastuzumab therapy. Oncol Nurs Forum. 2006;33(2):265–72.PubMedCrossRefGoogle Scholar
  42. 42.
    Paik S, Kim C, Jeong J. Benefit from adjuvant trastuzumab may not be confined to patients with IHC 3+ and/or FISH-positive tumors: Central testing results from NSABP B-31. J Clin Oncol. 2007;25(18S):511.Google Scholar
  43. 43.
    Garrison L, Lubeck D, Lalla D, Paton V, Dueck A, Perez EA. Cost-effectiveness analysis of trastuzumab in the adjuvant setting for treatment of HER2-positive breast cancer. Am J Clin Oncol. 2007;110:489–98.Google Scholar
  44. 44.
    Kurian A, Thompson R, Gaw A, Arai S, Ortiz R, Garber A. A cost-effectiveness analysis of adjuvant trastuzumab regimens in early HER2/neu-positive breast cancer. J Clin Oncol. 2007;25(6):634–41.PubMedCrossRefGoogle Scholar
  45. 45.
    Liberato N, Marchetti M, Barosi G. Cost effectiveness of adjuvant trastuzumab in human epidermal growth factor receptor 2-positive breast cancer. J Clin Oncol. 2007;25(6):625–33.PubMedCrossRefGoogle Scholar
  46. 46.
    Perez EA, Suman VJ, Davidson NE, et al. HER2 testing by local, central, and reference laboratories in the NCCTG N9831 Intergroup Adjuvant Trial. J Clin Oncol. 2006;24(19):3032–8.PubMedCrossRefGoogle Scholar
  47. 47.
    Paik S, Bryant J, Tan-Chiu E, et al. Real-world performance of HER2 testing-National Surgical Adjuvant Breast and Bowel Project experience. J Natl Cancer Inst. 2002;94:852–4.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2009

Authors and Affiliations

  • Edith A. Perez
    • 1
  • Frances M. Palmieri
    • 2
  • Shelly M. Brock
    • 2
  1. 1.Division of Hematology/OncologyInternal Medicine, Mayo ClinicJacksonvilleUSA
  2. 2.Division of Hematology/Oncology and Breast ClinicMayo ClinicJacksonvilleUSA

Personalised recommendations