Comparison of HER-2 status between primary breast cancer and corresponding distant metastatic sites

Ann Oncol. 2002 Jul;13(7):1036-43. doi: 10.1093/annonc/mdf252.


Background: The humanized anti-HER-2 monoclonal antibody trastuzumab (Herceptin) is a new treatment modality for metastatic breast cancer, the efficacy of which is directly correlated with the HER-2 status of the tumour, evaluated either by immunohistochemistry (IHC) and/or by fluorescence in situ hybridisation (FISH). This analysis is generally performed on the primary tumour. There are few data regarding the HER-2 status in the corresponding distant metastases.

Methods: HER-2 status in 107 patients with a primary breast tumour and at least one distant metastatic lesion was analysed by IHC and FISH.

Results: We found similar levels of amplification (25% and 24%) and overexpression (13% and 19%) of HER-2 in primary and metastatic samples, respectively. Among paired primary/metastatic tumours, six (6%) showed discordance by HercepTest(TM) (n = 100): all six cases showed greater Her-2 overexpression in the metastatic tissue. By FISH (n = 68), five (7%) cases were discordant: two cases were amplified in the primary tumour but not in the metastasis, and three samples showed amplification in the metastasis but not in the primary. Finally, we analysed HER-2 status in different metastatic lesions from 17 patients that had at least two distant metastatic sites. Discordance between different sites from the same patient was 18% by IHC and 19% by FISH.

Conclusions: Between the paired primary tumour and distant metastatic lesions, 94% and 93% of samples had concordant HER-2 status when analysed by IHC or FISH, respectively. These results do not support routine determination of HER-2 on metastatic sites, particularly when FISH results from the primary tumour are available.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers, Tumor / analysis*
  • Biopsy, Needle
  • Breast Neoplasms / pathology*
  • Cohort Studies
  • Confidence Intervals
  • Culture Techniques
  • Female
  • Humans
  • Immunohistochemistry
  • In Situ Hybridization, Fluorescence
  • Neoplasm Metastasis / pathology*
  • Neoplasm Staging
  • Neoplasms, Multiple Primary / pathology*
  • Prognosis
  • Receptor, ErbB-2 / analysis*
  • Sampling Studies
  • Sensitivity and Specificity


  • Biomarkers, Tumor
  • Receptor, ErbB-2