Skip to main content
SpringerLink
Log in

HER2+ breast cancer: How to evaluate?

  • Published:
Advances in Therapy Aims and scope Submit manuscript

Abstract

Approximately 15%–30% of breast cancers have overexpression or amplification of human epidermal growth factor receptor 2 (HER2), which is associated with a worse prognosis in the absence of therapy. While HER2 testing is common there are issues associated with its sensitivity and specificity, which may impact the perceived usefulness of treatments. The objectives of this review are to understand the characteristics and peculiarities of HER2+ breast cancer, and to discuss the issues associated with the correlation of HER2 immunogenicity with therapeutic response, especially of trastuzumab. There are two issues associated with the correlation between HER2 immunogenicity and therapeutic response: possible resistance to trastuzumab through lack of phosphatase and tensin analog or receptor expression, and nonspecific or insensitive measurement of HER2 expression. These issues can be addressed through the evaluation of other factors in addition to HER2 status at diagnosis, and improvements in the performance and validation of HER2 testing. It is important that HER2 tests are of the highest quality and that laboratories performing the tests are assessed and validated correctly. Pathologists must proactively monitor the quality of their tests and oncologists should ensure that all breast cancer cases are assessed for HER2, as only then can the patients benefit from specific and appropriate therapy.

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

References

  1. Li CI, Uribe DJ, Daling JR. Clinical characteristics of different histologic types of breast cancer. Br J Cancer. 2005;93:1046–1052.

    Article  PubMed  CAS  Google Scholar 

  2. Li CI, Moe RE, Daling JR, et al. Risk of mortality by histologic type of breast cancer among women aged 50 to 79 years. Arch Intern Med. 2003;163:2149–2153.

    Article  PubMed  Google Scholar 

  3. Brenton J, Carey L, Ahmed AA, et al. Molecular classification and molecular forecasting of breast cancer: ready for clinical application? J Clin Oncol. 2005;23:7350–7360.

    Article  PubMed  CAS  Google Scholar 

  4. Rakha EA, Tan DS, Foulkes WD et al. Are triple-negative tumours and basal-like breast cancer synonymous? Breast Cancer Res. 2007;9:404.

    Article  PubMed  Google Scholar 

  5. King CR, Kraus MH, Aaronson SA, et al. Amplification of a novel v-erbB-related gene in a human mammary carcinoma. Science. 1985;229:974–976.

    Article  PubMed  CAS  Google Scholar 

  6. Karunagaran D, Tzahar E, Beerli RR, et al. ErbB-2 is a common auxiliary subunit of NDF and EGF receptors: implications for breast cancer. EMBO J. 1996;15:254–264.

    PubMed  CAS  Google Scholar 

  7. Hynes NE, Lane HA. ERBB receptors and cancer: the complexity of targeted inhibitors. Nat Rev Cancer. 2005;5:341–354.

    Article  PubMed  CAS  Google Scholar 

  8. Citri A, Yarden Y. EGF-ERBB signaling: towards the systems level. Nat Rev Mol Cell Biol. 2006;7:505–516.

    Article  PubMed  CAS  Google Scholar 

  9. Moasser M. The oncogene HER2: its signaling and transforming functions and its role in human cancer pathogenesis. Oncogene. 2007;26:6469–6487.

    Article  PubMed  CAS  Google Scholar 

  10. Yarden Y, Sliwkowski MX. Untangling the ErbB signalling network. Nat Rev Mol Cell Biol. 2001;2:127–137.

    Article  PubMed  CAS  Google Scholar 

  11. 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;235:177–182.

    Article  PubMed  CAS  Google Scholar 

  12. Ross JS, Fletcher JA, Linette GP, et al. The Her-2/neu gene and protein in breast cancer biomarker and target of therapy. Oncologist. 2003;8:307–325.

    Article  PubMed  CAS  Google Scholar 

  13. 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. Arch Pathol Lab Med. 2007;131:8–43.

    Google Scholar 

  14. Romond EH, Perez EA, Bryant J, et al. Trastuzumab plus adjuvant chemotherapy for operable HER2-positive breast cancer. N Engl J Med. 2005;353:1673–1684.

    Article  PubMed  CAS  Google Scholar 

  15. Piccart-Gebhart MJ, Procter M, Leyland-Jones B, et al. Trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer. N Engl J Med. 2005;353:1659–1672.

    Article  PubMed  CAS  Google Scholar 

  16. Slamon, D, Eiermann W, Robert N, et al. BCIRG 006: 2nd interim analysis phase III randomized trial comparing doxorubicin and cyclophosphamide followed by docetaxel (ACT) with doxorubicin and cyclophosphamide followed by docetaxel and trastsuzumab (ACTH) with docetaxel, carboplatin and trastuzumab (TCH) in HER2neu positive early breast cancer patients. Presented at: 29th Annual Meeting of the San Antonio Breast Cancer Symposium; Dec 14–18, 2006; San Antonio, TX, USA.

  17. 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;354:809–820.

    Article  PubMed  CAS  Google Scholar 

  18. The Herceptin Adjuvant (HERA) Trial Study Team: Trastuzumab following adjuvant chemotherapy in HER2-positive early stage breast cancer (HERA trial): disease-free and overall survival after 2 year follow-up. Presented as a late breaking abstract at: 42nd Annual Meeting of the American Society of Clinical Oncology, June 2–6, 2006; Atlanta, GA, USA.

  19. Pandolfi PP. Breast cancer—loss of PTEN predicts resistance to treatment. N Engl J Med. 2004;351:2337–2338.

    Article  PubMed  CAS  Google Scholar 

  20. Harris LN, You F, Schnitt SJ, et al. Predictors of resistance to preoperative trastuzumab and vinorelbine for HER2-positive early breast cancer. Clin Cancer Res. 2007;13:1198–1207.

    Article  PubMed  CAS  Google Scholar 

  21. Moasser MM. The oncogene HER2: its signaling and transforming functions and its role in human cancer pathogenesis. Oncogene. 2007;26:6469–6487.

    Article  PubMed  CAS  Google Scholar 

  22. Scaltriti M, Rojo F, Ocaña A, et al. Expression of p95HER2, a truncated form of the HER2 receptor, and response to anti-HER2 therapies in breast cancer. J Natl Cancer Inst. 2 2007;99:628–638.

    Article  CAS  Google Scholar 

  23. 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;118–145.

    Article  PubMed  CAS  Google Scholar 

  24. Perez EA, Suman VJ, Davidson NE, et al. HER2 testing by local, central, and reference laboratories in specimens from the North Central Cancer Treatment Group N9831 Intergroup Adjuvant Trial. J Clin Oncol. 2006;24:3032–3038.

    Article  PubMed  Google Scholar 

  25. Roche PC, Suman VJ, Jenkins RB. Concordance between local and central laboratory HER2 testing in the breast intergroup trial N9831. J Natl Cancer Inst. 2002;94:855–857.

    PubMed  Google Scholar 

  26. Paik S, Bryant J, Tan-Chiu E. Real-world performance of HER2 testing — national surgical adjuvant breast and bowel project experience. J Natl Cancer Inst. 2002;94:852–854.

    PubMed  Google Scholar 

  27. Milanezi F. [Avaliação do HER2/neu em carcinomas invasivos da mama: correlação entre estudo imunohistoquímico e hibridização in situ por fluorescência.] Masters Thesis, Faculdade de Medicina da Universidade do Porto, Porto, Portugal. 2004. In Portugu

    Google Scholar 

  28. Bilous M, Dowsett M, Hanna W, et al. Current perspectives on HER2 testing: a review of national testing guidelines. Mod Pathol. 2003;16:173–182.

    Article  PubMed  Google Scholar 

  29. Walker RA, Bartlett JM, Dowsett M, et al. HER2 testing in the UK: further update to recommendations. J Clin Pathol. 2008;61:818–824.

    Article  PubMed  CAS  Google Scholar 

  30. Ricardo SA, Milanezi F, Carvalho ST, et al. HER2 evaluation using the novel rabbit monoclonal antibody SP3 and CISH in tissue microarrays of invasive breast carcinomas. J Clin Pathol. 2007;60:1001–1005.

    Article  PubMed  Google Scholar 

  31. Milanezi F, Carvalho S, Schmitt F. EGFR/HER2 in breast cancer: a biological approach for molecular diagnosis and therapy. Expert Rev Mol Diagn. 2008;8:417–434.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. IPATIMUP, Institute of Molecular Pathology and Immunology and Medical Faculty, University of Porto, Porto, Portugal

    Fernando Schmitt

Authors
  1. Fernando Schmitt
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Fernando Schmitt.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Schmitt, F. HER2+ breast cancer: How to evaluate?. Adv Therapy 26 (Suppl 1), 1–8 (2009). https://doi.org/10.1007/s12325-009-0046-1

Download citation

  • Received:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12325-009-0046-1

Keywords

Search

Navigation