The human epidermal growth factor receptor 2 (HER2) gene is responsible for producing HER2 proteins. HER2 proteins are receptors that are present on some breast cancer cells. When they’re activated, these receptors signal breast cancer cells to divide and multiply. Normally, HER2 receptors regulate and control the growth of breast cells, keeping them at a healthy level.

However, the HER2 gene is overexpressed in about one in every five cases of breast cancer. This means that instead of having one copy of the gene from each parent, you have multiple HER2 genes. When this occurs, it’s known as HER2 gene amplification.

These additional genes then make too many HER2 receptors. This is known as HER2 protein receptor overexpression. Too many genes and too many receptors cause breast cells to grow and divide in an uncontrolled manner. This can lead to aggressive tumor growth.

Extra HER2 receptors promote the growth of breast cancer. HER2-positive breast cancers are often more aggressive than HER2-negative breast cancers. HER2-positive breast cancers are also more likely to recur.

There are therapies specifically designed to target the HER2 receptor that are very effective in treating HER2-positive breast cancer. This type of breast cancer isn’t likely to respond to hormone therapy.

If you have breast cancer, you need to know if your cancer is HER2-positive or HER2-negative. The result makes a big difference when it comes time to discuss your treatment options and outlook.

To determine if your breast cancer is HER2-positive, your doctor will order testing. Two types of tests approved for HER2 diagnosis are immunohistochemistry (IHC) and in situ hybridization (ISH).

Immunohistochemistry (IHC) Tests

Immunohistochemistry (IHC) tests are done to see if breast cancer cells have too many HER2 protein receptors. Results mean the following:

  • A result of 0 is negative.
  • A result of 1+ is also negative.
  • A result of 2+ is considered borderline.
  • A result of 3+ is positive.

During an IHC test, pathologists analyze breast tissue under the microscope. They use special stains to see how many receptors are present on the breast cancer cells. No further testing is required for a 0 or 1+ result. A 2+ result is considered equivocal or indeterminate. Further testing will be required.

In Situ Hybridization (ISH) Tests

If further testing is indicated, the next step is to have ISH testing. It’s important to have HER2 testing done by experienced pathologists in a central lab using FDA-approved testing kits to avoid inaccurate test results.

The two main types of ISH testing are fluorescence in situ hybridization (FISH) and bright-field ISH. FISH testing is considered the standard for HER2 testing. FISH testing is considered more accurate than bright-field ISH and looks at DNA to see how many copies of the genes exist. A positive FISH test is definitive. It’s extremely rare for a FISH test to return as uncertain or indeterminate. If this does happen, you may need to have another biopsy to repeat the test on a different sample.

To properly diagnose your HER2 status, your doctor will remove some breast tissue during a biopsy. In most cases, your doctor will use a local anesthetic to minimize pain. This tissue will be sent to the pathology lab for review. In some cases, the sample will need to be sent to an outside lab for testing. Make sure that the lab doing your pathology review reputable and credentialed. It’s important that the lab uses FDA-approved HER2 testing kits.

FISH testing is safe. In most cases, the testing will be done on tissue from your original biopsy and won’t require that you have any additional procedures. Most biopsies can be completed in a doctor’s office or radiology room using local anesthetic.

Although a biopsy may be uncomfortable, it’s a very safe procedure with little risks or complications. You may develop scar tissue around the biopsy site. You may also experience mild pain immediately following the biopsy. Talk with your doctor about the possible risks of a biopsy.

IHC testing is usually done first because it’s easier and more widely available. However if IHC testing is inconclusive FISH testing should be done. In most cases, FISH testing can confirm whether the cancer is HER2-positive or HER2-negative.

HER2 test results aren’t always accurate. If an initial FISH test is inconclusive or the results are considered borderline, your doctor may request an additional biopsy to test another sample. If your results come back negative, ask your doctor how confident they are in the lab that was used and in the results. Ask to see how many pathologists reviewed your sample. If only one pathologist saw your FISH test, ask if another pathologist can review your sample to confirm or possibly dispute the original finding.

Don’t be afraid to request more information about your FISH testing to make sure you’re comfortable with the results and what they mean for your treatment and outlook. Above all, make sure that your testing was done at an accredited facility using FDA approved testing kits. Don’t be afraid to ask for a second opinion or to send your sample to a lab of your choice.

The good news is that HER2 treatments are typically very effective for HER2-positive breast cancer. Though HER2-positive breast cancer is generally more aggressive than other types of breast cancer, the outlook for people with HER2 has improved greatly in recent years. This is due to new and effective treatments that specifically target HER2 receptors.

If you’ve recently been diagnosed with breast cancer, your doctor will likely request several types of tests to better understand how your cancer developed and what can be done to more effectively treat it. These tests should include a HER2 test. Make sure you understand the results before proceeding with treatment.

If your breast cancer returns after your initial treatment, ask your doctor about the need to conduct a HER2 test. Unfortunately, breast cancers that return may change their HER2 status. What was once HER2-negative may be HER2-positive when it returns. If a cancer is diagnosed as HER2-positive, the treatments are very effective. Understanding your diagnosis and treatment options is important. Talk to your doctor to learn more.