HER2 Status
The HER2 (human epidermal growth factor receptor 2) gene makes HER2 proteins (also called HER2/neu proteins). HER2 proteins are receptors on breast cells. HER2 receptors help control how a breast cell grows, divides, and repairs itself.
What is HER2-positive breast cancer?
In about 10% to 20% of breast cancers, the HER2 gene doesn't work correctly and makes too many copies of itself (known as HER2 gene amplification). All these extra HER2 genes tell breast cells to make too many HER2 receptors (HER2 protein overexpression). This makes breast cells grow and divide in an uncontrolled way.
Breast cancers with too many copies of the HER2 gene or too many HER2 proteins are called HER2-positive in your pathology report. HER2-positive breast cancers tend to grow faster and are more likely to spread and come back compared to HER2-negative breast cancers. But there are medicines specifically for HER2-positive breast cancers.
The HER2 gene is also called the ERBB2 (Erb-B2 receptor tyrosine kinase 2) gene, so you may see it referred to by that name in some studies.
What is HER2-negative breast cancer?
HER2-negative breast cancers have normal levels of HER2 proteins. These cancers usually don’t respond to medicines for HER2-positive breast cancers.
What is HER2-low and -ultralow breast cancer?
More than half of breast cancers considered HER2-negative have some extra HER2 proteins on the surface of their cells. There just aren’t enough HER2 proteins for the cancer to be considered HER2-positive. Many doctors now call these cancers HER2-low or -ultralow.
Still, there is some controversy about whether HER2-low and -ultralow breast cancer are distinct subtypes.
HER2 tests
There are several tests used to find out if breast cancer is HER2-positive. How your results appear in your pathology report depend on the test you have. Two of the most common tests are the IHC test and the FISH test. Generally, only cancers that test IHC 3+ or FISH positive are considered HER2-positive and are most likely to respond to the medicines that target HER2-positive breast cancers.
Research has shown that some breast cancers that are HER2-positive can become HER2-negative over time or if they come back (recur). Likewise, a HER2-negative breast cancer can become HER2-positive over time. If the breast cancer comes back in the future, your doctor should consider ordering another biopsy to retest the cancer’s HER2 status.
The IHC test (ImmunoHistoChemistry) uses a chemical dye to stain the HER2 proteins. The IHC gives a score of 0 to 3+ that reflects the amount of HER2 proteins on the surface of cells in a breast cancer tissue sample.
If the score is 0 to 1+, the cancer may be considered HER2-negative.
If the score is 2+, it's called borderline or equivocal. If the IHC test results are borderline, it’s likely that a FISH test will be done on a sample of the cancer tissue to determine if the cancer is HER2-positive.
A score of 3+ is considered HER2-positive.
The FISH test (Fluorescence In Situ Hybridization) uses special labels that attach to the actual HER2 genes instead of the HER2 proteins on the surface of the cell. The special labels have chemicals added to them so they change color and glow in the dark when they attach to the HER2 genes. The laboratory counts the number of genes and decides whether there are more copies than normal. This test is the most accurate, but it is more expensive and takes longer to return results. This is why an IHC test is usually the first test done to see if a cancer is HER2-positive. With the FISH test, you get a score of either positive or negative (some hospitals call a negative test result zero).
HER2-low and -ultralow test results
An IHC score of 1+ or 2+ with a negative FISH test result is considered HER2-low and an IHC score of 0 with membrane staining is considered HER2-ultralow by many doctors and researchers. Still there is no official definition of HER2-low and -ultralow breast cancer.
HER2 testing accuracy
Research has shown that some HER2 status test results may be wrong. This is probably because different labs have different rules for classifying positive and negative HER2 status. Each pathologist also may use slightly different criteria to decide whether the results are positive or negative. In most cases, this happens when the test results are borderline — meaning they aren't strongly HER2-positive or HER2-negative.
In other cases, tissue from one area of a breast cancer can test HER2-positive and tissue from a different area of the cancer can test HER2-negative.
Inaccurate HER2 test results may cause people diagnosed with breast cancer to not get the best care possible. If all or part of a breast cancer is HER2-positive but test results classify it as HER2-negative, doctors aren't likely to recommend anti-HER2 treatment — even though a person could potentially benefit from those medicines. If a breast cancer is HER2-negative but test results classify it as HER2-positive, doctors may recommend anti-HER2 treatment — even though the person is unlikely to get any benefits and is exposed to the medicines' risks.
If your HER2 test results are HER2-negative, you may want to ask your doctor about how confident they are in the lab that did the HER2 testing and if another HER2 test might make sense for your unique situation. If your HER2 test results are borderline, it's a good idea to ask if another HER2 test makes sense for you.
Treatments for HER2-positive breast cancer
There are a number of treatments available specifically for HER2-positive breast cancer.
Learn more about anti-HER2 medicines.
— Last updated on March 29, 2025 at 3:37 PM