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HER2 testing in a population-based study of patients with metastatic breast cancer treated with trastuzumab
Frances P O'Malley1, Tom Thomson, Jim Julian
1Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, 600 University Ave, Toronto, Ontario, Canada M5G 1X5. fomalley@mtsinai.on.ca
Context:
The development of trastuzumab has led to new therapeutic strategies for patients with breast cancer. Trastuzumab has been shown to only be effective in those patients whose cancers are HER2 positive by either immunohistochemistry (IHC) or fluorescence in situ hybridization (FISH).
Objective:
To determine the accuracy of HER2 testing in 2 provinces in Canada.
Design:
Patients with metastatic breast cancer diagnosed between 1999 and 2002 who were HER2 positive in the local laboratories were included in this study. All cases were retested centrally, by IHC (using 4 methods) and FISH. In addition, 205 locally reported HER2-negative metastatic breast cancer cases were retested centrally.
Results:
Concordance between the 505 local IHC-positive cases with central IHC testing varied between 79.3% and 89.6% depending on the IHC method and scoring method used. HER2 gene amplification by FISH was present in 86.1% of local IHC-positive cases. Concordance between the 205 local IHC-negative tumors with central testing ranged between 94.8% and 100% for IHC and was 98.5% for FISH.
Conclusions:
This study demonstrated that locally reported HER2-negative results were highly accurate, but less accuracy was demonstrated with local HER2-positive results. These results emphasize the need for participation in a quality assurance program.
Insights
Accurate HER2 testing is crucial for trastuzumab treatment in breast cancer. This study found local HER2-negative results highly accurate, but local HER2-positive results varied, highlighting the need for quality assurance programs.
Area of Science:
- Oncology
- Pathology
- Biomarker Testing
Background:
- Trastuzumab efficacy in breast cancer is limited to HER2-positive cases.
- Accurate human epidermal growth factor receptor 2 (HER2) testing is essential for guiding trastuzumab therapy.
- HER2 status is determined by immunohistochemistry (IHC) or fluorescence in situ hybridization (FISH).
Purpose of the Study:
- To evaluate the accuracy of local HER2 testing in Canadian provinces.
- To compare central laboratory testing with local diagnostic results for HER2 status.
Main Methods:
- Retrospective analysis of metastatic breast cancer cases diagnosed between 1999-2002.
- Centralized retesting of locally HER2-positive cases (n=505) using four IHC methods and FISH.
- Centralized retesting of locally HER2-negative cases (n=205) using IHC and FISH.
Main Results:
- Concordance for locally HER2-positive cases with central IHC ranged from 79.3% to 89.6%.
- HER2 gene amplification by FISH was confirmed in 86.1% of local IHC-positive cases.
- Concordance for locally HER2-negative cases was high, ranging from 94.8% to 100% for IHC and 98.5% for FISH.
Conclusions:
- Local HER2-negative test results demonstrated high accuracy.
- Local HER2-positive test results showed variable accuracy, indicating potential for discrepancies.
- Participation in a quality assurance program is recommended to improve HER2 testing consistency.
