From the Guidelines
HER2 status is determined through tissue testing using immunohistochemistry (IHC) and/or fluorescence in situ hybridization (FISH). The most recent and highest quality study 1 supports the use of both IHC and FISH for determining HER2 status. IHC measures the amount of HER2 protein on cancer cells, scoring results from 0 to 3+, with scores of 0 and 1+ considered negative, 2+ equivocal, and 3+ positive. When IHC results are equivocal (2+), FISH testing is performed to detect HER2 gene amplification by measuring the number of HER2 gene copies. FISH results are reported as positive or negative based on the ratio of HER2 gene copies to chromosome 17 copies, with a ratio ≥2.0 considered positive.
Some key points to consider when determining HER2 status include:
- The accuracy of HER2 assays used in clinical practice is a major concern, and results from several studies have shown that false-positive and false-negative HER2 test results are common 1.
- The guidelines describe strategies for evaluating tumors with borderline or indeterminate HER2 status 1.
- HER2 testing should be performed only in laboratories accredited to perform such testing, and these laboratories should have standardized HER2 testing procedures established, and programs to periodically evaluate the proficiency of personnel performing HER2 testing 1.
- Clinicians should be familiar with the significance of these criteria when making individual clinical recommendations 1.
These tests are typically performed on tissue samples obtained during biopsy or surgery. Accurate HER2 testing is crucial because it guides treatment decisions, particularly regarding HER2-targeted therapies like trastuzumab, pertuzumab, and T-DM1, which are effective only in HER2-positive cancers. Testing should be performed at diagnosis for all invasive breast cancers and may be repeated if there is disease recurrence or progression to assess for possible changes in HER2 status.
From the FDA Drug Label
Assessment of HER2 protein overexpression and HER2 gene amplification should be performed using FDA-approved tests specific for breast cancer by laboratories with demonstrated proficiency Information on the FDA-approved tests for the detection of HER2 protein overexpression and HER2 gene amplification is available at: http://www.fda. gov/CompanionDiagnostics.
The HER2 status is determined by assessing HER2 protein overexpression and HER2 gene amplification in tumor specimens using FDA-approved tests. Key points to note:
- The tests should be specific for breast cancer.
- The tests should be performed by laboratories with demonstrated proficiency.
- Information on FDA-approved tests is available at the FDA website 2.
From the Research
Determining HER2 Status
The HER2 status can be determined by several methods, including:
- Fluorescence In Situ Hybridization (FISH) 3, 4, 5, 6
- Immunohistochemistry (IHC) 3, 4, 7, 5, 6
- Chromogenic In Situ Hybridization (CISH) 7
- Silver-enhanced In Situ Hybridization (SISH) 7
- Quantitative real-time RT-PCR 7
Comparison of Methods
Studies have compared the concordance between FISH and IHC results, with varying degrees of agreement:
- One study found a concordance rate of 82% between FISH and IHC results 5
- Another study found a highly significant concordance between FISH and IHC results, but noted that IHC's subjective grading system precludes its use as a gold standard 4
- A study found that FISH was superior to IHC in determining HER2 status, with FISH correlating with clinical outcomes such as overall survival and metastases/recurrence 3
Clinical Significance
The determination of HER2 status is critical in breast cancer, as it can inform treatment decisions and predict patient outcomes: