> For the complete documentation index, see [llms.txt](https://help.dragen.illumina.com/llms.txt). Markdown versions of documentation pages are available by appending `.md` to page URLs; this page is available as [Markdown](https://help.dragen.illumina.com/dragen-v4.6/product-guides/dragen-v4.6/dragen-dna-pipeline/biomarkers/biomarker-her2-amplification.md).
# HER2 Amplification
## Description
By default, DRAGEN estimates HER2 (ERBB2) amplification status for research use, using its focal gene copy number calling module with thresholds similar to College of American Pathologists (CAP) testing guidelines for breast cancer. For more information on the details of this method, see [Focal Gene Copy Number Calling](/dragen-v4.6/product-guides/dragen-v4.6/dragen-dna-pipeline/cnv-overview/cnv-somatic.md#focal-gene-amplification).
> DRAGEN HER2 amplification estimation is intended for research use only and is not for use in diagnostic procedures.
## Demonstration of Accuracy
The data below describe analytical performance evaluated in a research validation study. They are not intended to support clinical diagnostic use.
### Experimental Design
Focal gene amplification was tested on a cohort of 623 breast cancer samples with HER2 (ERBB2) amplification status established using CAP standard IHC and FISH testing as the reference method. NGS sequencing was tumor-only WES, performed at a reference sequencing laboratory. DRAGEN was run using default definitions for the HER2 region and control region (p-arm of chr17) on hg38.
To align as closely as possible with FISH/IHC reference results, the following thresholds were used to determine DRAGEN WES-based calls:
| Call | Description |
| --------- | --------------------------------------------------------- |
| Positive | Her2CN $\geq$ 6 or SMRatio $\geq$ 2 |
| Negative | Her2CN < 6 and SMRatio < 1.8 |
| Equivocal | Otherwise |
### Performance
The table below shows the performance of DRAGEN focal gene copy number assessment on HER2 relative to histology (reference derived from the combination of IHC and FISH).
| | DRAGEN Negative | DRAGEN Positive | DRAGEN Equivocal |
| ------------------ | --------------- | --------------- | ---------------- |
| Histology Negative | 538 | 6 | 13 |
| Histology Positive | 3 | 59 | 4 |
The following table summarizes overall analytical sensitivity and specificity relative to the IHC/FISH reference.
| Metric | Value (%) |
| ---------------------- | ------------- |
| Analytical sensitivity | 95% (59/62) |
| Analytical specificity | 99% (538/544) |
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