HER2: Definition

HER2 (human epidermal growth factor receptor 2) is a protein found on the surface of many cells in the body. In healthy cells, HER2 acts like an antenna. It receives growth signals from the surrounding environment and passes them into the cell, helping to control when the cell grows and divides. Normally, each cell carries two copies of the HER2 gene and makes a modest, carefully regulated amount of the HER2 protein.

In some cancers, the HER2 gene is amplified, meaning the cancer cell has made far too many copies of it, sometimes dozens. With so many extra copies of the gene, the cell produces a very large amount of HER2 protein. The surface of the cancer cell becomes covered in HER2 receptors, all sending growth signals at once. The result is a cell that grows and divides much faster than normal. HER2 is one of the most useful biomarkers in cancer care, because whether this change is present in a tumor directly affects which treatments are most likely to work. This article explains what HER2 means on a pathology report, how it is tested, and what the different results mean.

Which cancers are tested for HER2?

HER2 testing looks for extra copies of the HER2 gene or excess HER2 protein in a tumor. It is performed most often in the following cancers:

Breast cancer — About 15 to 20% of breast cancers are HER2-positive. HER2 testing is standard for every newly diagnosed breast cancer. For full details, see the guide on HER2 in breast cancer.
Gastric (stomach) and gastroesophageal junction cancer — About 10 to 15% of these cancers are HER2-positive. HER2-targeted therapy is approved for advanced HER2-positive gastric cancer.
Colorectal cancer — HER2 amplification is found in a small share of colorectal cancers, most often those without KRAS or BRAF mutations. For full details, see the guide on HER2 in colorectal cancer.
Esophageal adenocarcinoma, endometrial cancer, bladder cancer, and others — HER2 testing is performed across a growing number of cancer types as HER2-targeted treatments continue to be studied and approved.

How is HER2 tested?

HER2 is measured on tumor tissue taken during a biopsy or surgery. Pathologists use two main tests to measure HER2 status, and they are often used in sequence:

Immunohistochemistry (IHC) — Measures the amount of HER2 protein on the surface of the cancer cells. A special stain is applied to a thin slice of tumor tissue, and the pathologist scores how much staining is present. IHC is almost always the first test performed.
FISH (fluorescence in situ hybridization) — Counts the actual number of HER2 gene copies inside the cancer cells using fluorescent probes that light up under the microscope. FISH is used to sort out uncertain IHC results.

The exact scoring rules differ slightly from one cancer type to another (for example, breast and gastric cancers use somewhat different criteria). The dedicated guides linked above describe the rules for each cancer.

How are HER2 results reported?

HER2 IHC results are scored on a scale from 0 to 3+, based on how strongly the HER2 protein stains in the tumor cells:

0 — No staining, or faint, incomplete staining. Very little or no HER2 protein is detected. In most cancers, this is reported as HER2-negative. In breast cancer, a score of 0 with faint partial staining of the cell borders may now be reported as HER2-ultralow (explained below).
1+ — Faint or incomplete staining. This is HER2-negative by the traditional cut-off. In breast cancer, a score of 1+ is reported as HER2-low, a separate category that can affect treatment options.
2+ — Moderate staining. The result is borderline (called equivocal) and cannot classify the tumor on its own. A FISH test is usually performed to count HER2 gene copies and decide whether true amplification is present.
3+ — Strong, complete staining in more than 10% of tumor cells. The cancer is HER2-positive.

If FISH is performed, it is reported as:

Amplified (positive) — The cancer cells carry extra HER2 gene copies. Combined with a 2+ IHC result, this confirms the cancer is HER2-positive.
Not amplified (negative) — A normal number of HER2 gene copies. Combined with a 2+ IHC result, this confirms the cancer is HER2-negative (or, in breast cancer, HER2-low).

What do HER2-low and HER2-ultralow mean?

HER2-low and HER2-ultralow are terms used mainly in breast cancer. They describe tumors that make a small amount of HER2 protein: less than a HER2-positive cancer, but more than none.

HER2-low — An IHC score of 1+, or a score of 2+ with FISH showing no amplification.
HER2-ultralow — An IHC score of 0 with faint, partial staining of the cell borders. This is a newer category.

These cancers were once grouped together with HER2-negative cancers. They are now identified separately because a drug called trastuzumab deruxtecan (Enhertu) can attach to even small amounts of HER2 on the cell surface and carry chemotherapy directly into the cell. For breast cancer that has spread (metastatic disease), a HER2-low or HER2-ultralow result can open the door to this treatment after other therapies have been tried. HER2-low and HER2-ultralow cancers are not treated with the older HER2-targeted drugs, such as trastuzumab and pertuzumab, in the same way that HER2-positive cancers are. Whether any of these options fit a person’s situation is a decision made with the medical oncology team.

What does a HER2-positive result mean?

A HER2-positive result means the cancer makes a large amount of HER2 protein, usually because the HER2 gene is amplified. These cancers may respond to HER2-targeted therapies, drugs designed to attach to the HER2 protein or block the growth signals it sends. Examples include trastuzumab (Herceptin), pertuzumab (Perjeta), and trastuzumab deruxtecan (Enhertu). These drugs work very differently from standard chemotherapy and, in HER2-positive cancers, have greatly improved outcomes.

Because HER2-targeted drugs work only when HER2 is present, they are not used for HER2-negative cancers. This is why HER2 testing is done before these treatments are considered. A HER2-positive result helps the treatment team decide whether HER2-targeted therapy is an option.

Since 2024, one HER2-targeted drug (trastuzumab deruxtecan) has also been approved in the United States as a tumor-agnostic treatment. This means it can be considered for many different HER2-positive (IHC 3+) advanced solid tumors, regardless of where in the body the cancer started, after other treatments have been tried. Which HER2-positive cancers this applies to, and whether it fits a particular person, is decided by the medical oncology team based on the full pathology report and clinical situation.

Questions to ask your doctor

Was my tumor tested for HER2, and what was the IHC score?
If the IHC score was 2+, was FISH testing performed, and did it show amplification?
Is my cancer HER2-positive, HER2-negative, HER2-low, or HER2-ultralow?
Does my HER2 result make me eligible for any HER2-targeted therapy?
If my cancer is HER2-low or HER2-ultralow, are there treatment options that target it?
Could my HER2 result change if the cancer comes back or spreads, and would it be tested again?
Are there clinical trials of HER2-targeted treatments that I might qualify for?