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Comparison of HER-2 status between primary breast cancer and corresponding distant metastatic sites
D Gancberg1, A Di Leo, F Cardoso
1Translational Research Unit and Data Centre, Jules Bordet Institute, Brussels, Belgium.
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.
Insights
HER-2 status in primary breast cancer and its metastases is largely consistent. Routine HER-2 testing on metastatic sites is not recommended when primary tumor results are available.
Area of Science:
- Oncology
- Molecular Diagnostics
- Cancer Therapeutics
Background:
- Trastuzumab efficacy in metastatic breast cancer correlates with HER-2 status.
- HER-2 testing is typically performed on primary tumors.
- Limited data exists on HER-2 status in distant metastases.
Purpose of the Study:
- To compare HER-2 status between primary breast tumors and their distant metastases.
- To assess the concordance of HER-2 status in paired primary and metastatic samples.
- To evaluate discordance rates in HER-2 status within different metastatic sites of the same patient.
Main Methods:
- HER-2 analysis using immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH).
- Paired primary tumor and metastatic lesion samples from 107 patients.
- Analysis of HER-2 status in multiple metastatic sites from 17 patients.
Main Results:
- High concordance (94% IHC, 93% FISH) between primary tumors and metastases.
- Low discordance rates observed in paired samples (6% IHC, 7% FISH).
- Intra-patient discordance between metastatic sites was 18% (IHC) and 19% (FISH).
Conclusions:
- HER-2 status is generally consistent between primary breast tumors and distant metastases.
- Routine HER-2 testing on metastatic sites is not supported when primary tumor results are available.
- FISH analysis of primary tumors provides reliable HER-2 status for treatment decisions.
