HER2 (human epidermal growth factor receptor 2) is a gene that can play a role in the development of breast cancer. Your pathology report should include information about HER2 status, which tells you whether or not HER2 is playing a role in the cancer.
Genes contain the recipes for the various proteins a cell needs to stay healthy and function normally. Some genes and the proteins they make can influence how a breast cancer behaves and how it might respond to a specific treatment. Cancer cells from a tissue sample can be tested to see which genes are normal and abnormal. The proteins they make can also be tested.
The HER2 gene makes HER2 proteins (also sometimes referred to as HER2/neu proteins). HER2 proteins are receptors on breast cells. Normally, HER2 receptors help control how a healthy breast cell grows, divides, and repairs itself. But 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 HER2 gene amplification or HER2 protein overexpression are called HER2-positive in the 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.
Testing for HER2 status
There are several tests used to find out if breast cancer is HER2-positive. How your results appear in the report will depend on the test you have. Two of the most common tests are:
- IHC test (ImmunoHistoChemistry): The IHC test uses a chemical dye to stain the HER2 proteins. The IHC gives a score of 0 to 3+ that measures the amount of HER2 proteins on the surface of cells in a breast cancer tissue sample. If the score is 0 to 1+, it’s considered HER2-negative. If the score is 2+, it's considered borderline. A score of 3+ is considered HER2-positive. 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.
- FISH test (Fluorescence In Situ Hybridization): The FISH test uses special labels that attach to the HER2 proteins. The special labels have chemicals added to them so they change color and glow in the dark when they attach to the HER2 proteins. 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”).
It's important to know which HER2 test you had. Generally, only cancers that test IHC 3+ or FISH positive respond to the medicines that target HER2-positive breast cancers. An IHC 2+ test result is called borderline. If you have an IHC 2+ result, ask to have the tissue retested with the FISH test.
Research has shown that some breast cancers that are HER2-positive can become HER2-negative over time. Likewise, a HER2-negative breast cancer can become HER2-positive over time. If the breast cancer comes back in the future as advanced disease, doctors should consider ordering another biopsy and retest the tissue’s HER2 status.
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.
Treatments for HER2-positive breast cancer
There are some treatments available specifically for HER2-positive breast cancer. They are:
- Enhertu (chemical name: fam-trastuzumab-deruxtecan-nxki), a combination of an anti-HER2 medicine that has the same basic structure as Herceptin, the chemotherapy medicine topoisomerase I inhibitor, and deruxtecan, a compound that links the other two together. Enhertu was designed to deliver topoisomerase I inhibitor to cancer cells in a targeted way by attaching the topoisomerase I inhibitor to the anti-HER2 medicine, which then carries the chemotherapy to the HER2-positive cancer cells.
- Herceptin (chemical name: trastuzumab), which works against HER2-positive breast cancers by blocking the ability of the cancer cells to receive chemical signals that tell the cells to grow.
- Kadcyla (chemical name: T-DM1 or ado-trastuzumab emtansine), a combination of Herceptin and the chemotherapy medicine emtansine. Kadcyla was designed to deliver emtansine to cancer cells in a targeted way by attaching emtansine to Herceptin. Herceptin then carries emtansine to the HER2-positive cancer cells.
- Nerlynx (chemical name: neratinib), which fights HER2-positive breast cancers by blocking the cancer cells' ability to receive growth signals.
- Perjeta (chemical name: pertuzumab); like Herceptin, Perjeta works against HER2-positive breast cancers by blocking the cancer cells’ ability to receive growth signals.
- Tykerb (chemical name: lapatinib), which works against HER2-positive breast cancers by blocking certain proteins that can cause uncontrolled cell growth.
For more information on these HER2-targeted therapies, visit the Breastcancer.org Targeted Therapies section.
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 women 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 the woman could potentially benefit from Herceptin, Kadcyla, Perjeta, or Tykerb. If a breast cancer is HER2-negative but test results classify it as HER2-positive, doctors may recommend anti-HER2 treatment — even though the woman 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 he or she is 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.
American Cancer Society. Breast Cancer Facts & Figures 2019-2020. Available at: www.cancer.org/content/dam/cancer-org/research/cancer-facts-and-statistics/breast-cancer-facts-and-figures/breast-cancer-facts-and-figures-2019-2020.pdf
American Society of Clinical Oncology. Breast Cancer Guide. July 2019. Available at: www.cancer.net/cancer-types/breast-cancer/introduction.
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