HER2 ISH Summary
Description
HER2 in situ hybridization (ISH) Summary is the summary score for results of testing for ERBB2 gene copy number by any ISH method. An immunohistochemistry (IHC) test identifies the protein expressed by the gene (ERBB2), and an ISH test identifies the number of copies of the gene (ERBB2) itself.
If an Immunochemistry (IHC) test is borderline or indeterminate, an ISH test may be performed. The ISH test is a method of testing for overexpression of the HER2 gene that uses fluorescent pieces of DNA that attach only to the HER2 gene copies in cells, which can then be counted under a special microscope. ISH studies determine the presence or absence of gene amplification and methods include fluorescence in situ hybridization (FISH), chromogenic in situ hybridization (CISH), and silver-enhanced in situ hybridization (SISH). Some assays use a single probe to determine the number of HER2 gene copies present (single-probe assays) and others include a chromosome enumeration probe (CEP17) to determine the ratio of HER2 signals to copies of chromosome 17 (dual-probe assays).
Results from single probe and dual probe ISH tests are reported differently and are collected in different data items. For dual probe tests, both HER2/CEP17 ratio and HER2 copy number results are collected in separate data items.
Rationale
HER2 ISH Summary is a Registry Data Collection Variable in AJCC. It is a new data item for cases diagnosed 1/1/2018-12/31/2020 and 1/1/2027+.
Overexpression and / or amplification of the HER2 (cErbB2) gene is a key prognostic factor for breast cancer and a critical marker to define treatment. Historically, HER2 status has been a dichotomous “negative” or “positive” and rarely “equivocal” based on guidelines set forth by a joint American Society of Clinical Oncology and the College of American Pathologists task force (1). This determination is based on an algorithm using results of HER2 immunohistochemistry (IHC) and in situ hybridization (ISH). Those tumors with IHC 0 or 1+ are classified as “HER2 negative” and those with IHC 3+ as HER2 positive. Tumors that are IHC 2+ should undergo ISH testing for HER2 gene amplification. IHC 2+ cancer are classified as negative or positive based on the absence or presence of HER2 gene amplification, respectively. This dichotomous result, as reported by the physician, is used to determine AJCC TNM Stage.
As many as 50% of breast cancers are HER-2 low. It is therefore important to collect data that allows derivation of HER2-low in cancer registries because a) it is potentially a factor that will need to be incorporated into revisions of prognostic staging, and b) because HER2 is a key therapeutic target in breast cancer even when its expression is low. This will affect outcome analyses and understanding of the quality of care. While current use of ADCs with HER2-low cancer are approved only for those with metastatic cancer, it is likely that clinical trials already underway on ADC use in the adjuvant setting will provide practice-changing findings for this sub-type of breast cancer.
To accomplish this, registries need to collect the specific information on HER IHC (0, 1+, 2+, 3+) and ISH (amplified or not amplified). Simply recording “HER2-low” will be insufficient because a) this is not used in CAP Protocol; and b) current staging and treatment are based on the “negative” vs. “positive”, and c) standards for derivation of this may change and the granular information will be needed and d) reporting at the hospital levels of HER2-low may vary widely.
Additional Info
* **Source documents:** pathology report
* **For further information,** refer to the **Breast Biomarker Reporting** cancer protocols published by the College of American Pathologists for the AJCC Staging System *Breast*.
Notes
**Note 1:** **This SSDI is required for years 2008-2020, 2027+**
* For cases diagnosed 2021-2026, this SSDI may be left blank
**Note 2:** **Physician Statement**
* Physician statement of HER2 ISH Summary status can be used to code this data item when no other information is available.
**Note 3:** **Criteria for coding**
* The HER2 ISH test performed on the primary breast tissue is to be recorded in this data item.
* Results from nodal or metastatic tissue may be used **ONLY** when there is no evidence of the primary tumor on physical exam, imaging, or pathology.
* **Note:** In-situ is evidence of cancer
**Note 4:** **Types of ISH tests**
* Any type of ISH test (e.g., FISH, CISH, SISH) can be used to code this data item
**Note 5:** **In-situ and Invasive components present**
* If HER2 is positive on an in-situ component and HER2 is negative on all tested invasive components in the primary tumor, code HER2 as negative (code 0)
* If in situ and invasive components present and HER2 only done on the in-situ component in the primary tumor, code unknown (code 9)
**Note 6:** **Single tumor, multiple biopsies or surgical resection, different results**
* Use the highest (positive, equivocal, or negative)
**Note 7:** **Multiple tumors, different results**
* Code the results from the largest tumor size (determined either clinically or pathologically) when multiple tumors are present.
* Do not use specimen size to determine the largest tumor size
**Note 8:** **Neoadjuvant Therapy**
* Record the assay from tumor specimens prior to neoadjuvant therapy.
* If neoadjuvant therapy is given and there are no ER results from pre-treatment specimens, report the findings from post-treatment specimens
**Note 9:** **ERBB2**
* An immunohistochemistry (IHC) test identifies the protein expressed by the gene (ERBB2), and an in situ hybridization (ISH) test identifies if there is amplification of the gene (ERBB2) itself
**Note 10:** **HER2 and in situ tumors**
* HER2 is not routinely done on pure in situ tumors (behavior /2); however, if you have an in-situ tumor and there are HER2 results, go ahead and record it. Otherwise, code 9
Default
8
Metadata
SSDI 2018–2020
| Code |
Description |
| 0 |
Negative [not amplified] |
| 2 |
Equivocal |
| 3 |
Positive [amplified] |
| 7 |
Test ordered, results not in chart |
| 8 |
Not applicable: Information not collected for this case
(If this item is required by your standard setter, use of code 8 will result in an edit error.) |
| 9 |
Not documented in medical record
Results cannot be determined (indeterminate)
Borderline
HER2 ISH Summary not assessed or unknown if assessed |
| <BLANK> |
May be blank if diagnosis year is 2021-2026 |
