HER2: Definition

by Jason Wasserman MD PhD FRCPC
April 7, 2026

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 produces a modest, 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 an enormous amount of HER2 protein. The surface of the cancer cell becomes covered in HER2 receptors, all constantly sending growth signals. The result is a cell that grows and divides far more rapidly than normal. HER2 testing is performed to determine whether this change is present in your tumour, as it directly affects which treatments are most likely to work.

Which cancers are tested for HER2?

HER2 testing is most commonly performed in:

  • Breast cancer — approximately 15–20% of breast cancers are HER2-positive. HER2 testing is standard for all newly diagnosed breast cancers. For full details, see the dedicated guide on HER2 in breast cancer.
  • Gastric (stomach) and gastroesophageal junction cancer — approximately 10–15% 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 proportion of colorectal cancers, particularly those without KRAS or BRAF mutations. For full details, see the dedicated guide on HER2 in colorectal cancer.
  • Esophageal adenocarcinoma, endometrial cancer, bladder cancer, and others — HER2 testing is increasingly performed across several cancer types as HER2-targeted treatments continue to be studied and approved.

How is HER2 tested?

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 cancer cells. A special stain is applied to a thin slice of tumour 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 follow up on uncertain IHC results.

How results are reported

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

  • 0 (negative) — no meaningful HER2 protein detected. The cancer is HER2-negative, and HER2-targeted drugs are not indicated.
  • 1+ (negative) — faint or incomplete staining. The cancer is considered HER2-negative for most treatment purposes. In breast cancer, however, a score of 1+ is now sometimes described as HER2-low, a category that may qualify for certain newer antibody-drug treatments. Ask your oncologist whether this applies to you.
  • 2+ (equivocal) — moderate staining; the result is borderline and cannot be used alone to classify the tumour. A FISH test is usually performed to count HER2 gene copies and determine whether true amplification is present.
  • 3+ (positive) — strong, complete staining in more than 10% of tumour cells. The cancer is HER2-positive, and HER2-targeted therapy is indicated.

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.

What does a HER2-positive result mean for treatment?

A HER2-positive result means your cancer may respond to drugs called HER2-targeted therapies. These drugs are designed to bind to the HER2 protein or to interfere with its signaling, slowing or stopping cancer cell growth. Examples include trastuzumab (Herceptin), pertuzumab, and trastuzumab deruxtecan (Enhertu). These drugs work very differently from standard chemotherapy and, in HER2-positive cancers, have significantly improved outcomes. HER2-targeted therapy is not effective in HER2-negative cancers, which is why testing is essential before treatment decisions are made.

Questions to ask your doctor

  • Was my tumour tested for HER2, and what was the IHC score?
  • If the IHC score was 2+, was FISH testing performed, and what did it show?
  • Does my HER2 result make me eligible for HER2-targeted therapy?
  • If my result is HER2-low, does this open up any treatment options for me?

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