HER2 testing is a diagnostic procedure that checks a tumor tissue sample for the Human Epidermal Growth Factor Receptor 2 (HER2) protein, or the gene that creates it. The purpose is to determine if cancer cells are producing an excessive amount of the HER2 protein or have too many copies of the HER2 gene. The test is performed on tissue already collected from a biopsy or surgery, so a new procedure is not required.
The Role of HER2 in Cancer
Human Epidermal Growth Factor Receptor 2 is a protein on the surface of cells that helps regulate normal cell growth and division. In some cancers, a mutation in the HER2 gene leads to the creation of too many HER2 protein receptors on the cancer cells. This overabundance can cause the cells to grow and multiply uncontrollably, often resulting in more aggressive tumors.
This phenomenon is most commonly evaluated in breast, stomach (gastric), and esophageal cancers. Because cancers with high levels of HER2 tend to grow more quickly, testing for this marker is a standard part of the diagnostic process for these cancers.
Types of HER2 Tests
The two primary methods for this analysis are Immunohistochemistry (IHC) and In Situ Hybridization (ISH).
The IHC test is often the first test performed because it is faster and less expensive. This method measures the quantity of HER2 protein on the surface of cancer cells. The results are then assigned a score from 0 to 3+ that reflects the amount of protein detected.
The ISH test, most commonly performed as Fluorescence In Situ Hybridization (FISH), directly examines the genes within the cancer cells. This molecular test counts the number of copies of the HER2 gene. It uses a fluorescent probe that attaches to the gene, causing it to glow so it can be counted.
Interpreting Test Results
A tumor is considered HER2-positive if it has a high level of HER2 protein or too many copies of the HER2 gene. This corresponds to an IHC score of 3+ or a positive ISH test. These cancers tend to be more aggressive but are also more likely to respond to treatments that target the HER2 protein.
A HER2-negative result indicates that the cancer cells have a normal amount of HER2 protein and gene copies. This is defined by an IHC score of 0 or 1+. Cancers in this category do not respond to therapies designed to target HER2.
A newer classification is HER2-low, which applies to tumors with some HER2 protein but not enough to be classified as HER2-positive. A HER2-low status is defined by an IHC score of 1+, or an IHC score of 2+ combined with a negative ISH test result. If an IHC test returns a score of 2+, the result is considered borderline, and an ISH test is required for a conclusive result.
Implications for Cancer Treatment
A patient’s HER2 status helps determine if they are a candidate for targeted therapies, which are drugs designed to attack specific features of cancer cells. For HER2-positive cancer, treatments that block the HER2 protein receptors interfere with the signals that tell cancer cells to grow, which has significantly improved patient outcomes.
For the HER2-low category, new antibody-drug conjugates are emerging as effective options because they can target cells with lower levels of the HER2 protein. In cases of HER2-negative cancer, where targeted therapies are ineffective, the treatment plan will focus on other approaches like hormone therapy or chemotherapy.