The human epidermal growth factor receptor 2 (HER2) gene is responsible for producing HER2 proteins. HER2 proteins are present on the surface of some breast cancer cells. When they’re activated, they signal breast cancer cells to divide and multiply.

Normally, HER2 proteins regulate and control the growth of breast cells. But when the HER2 gene is mutated, which is the case in about 1 in every 5 cases of breast cancer, it makes too many HER2 proteins. This results in breast cells growing and dividing out of control.

This is referred to as HER2-positive breast cancer.

HER2-positive breast cancers are often more aggressive than HER2-negative breast cancers. They’re also more likely to recur. Fortunately, drugs are available that are specifically designed to target HER2. These drugs are very effective in treating this type of breast cancer.

If you have breast cancer, you need to know if your cancer is HER2-positive or HER2-negative. It’s important to get the tests that determine this. The result makes a big difference when it comes to your treatment options and outlook.

To determine if your breast cancer is HER2-positive, your doctor will order testing that’s conducted on a tissue sample.

Two types of tests are approved for HER2 diagnosis: in situ hybridization (ISH or FISH) and immunohistochemistry (IHC).

In situ hybridization (ISH or FISH) tests

An in situ hybridization (ISH) test looks at the genetics of the sample, and the results of this test are also classified as positive, negative, or equivocal. An equivocal result requires further testing. Fluorescence in situ hybridization (FISH) is one type of ISH test.

Sometimes IHC testing is done first. But if IHC testing is inconclusive, an ISH test should be done. In many cases, an ISH test can confirm whether the cancer is HER2-positive or HER2-negative.

If an initial ISH test is inconclusive, an IHC can be done or a repeat ISH test on a new tissue sample may be needed. Your doctor may want to get an additional biopsy to test another sample. Sometimes, both IHC and ISH tests may be needed to confirm HER2 status.

Immunohistochemistry (IHC) tests

Immunohistochemistry (IHC) tests are done to see if breast cancer cells have too many HER2 protein receptors. How your doctor interprets this test is as follows:

  • A result of 0 is negative.
  • A result of 1+ is also negative.
  • A result of 2+ is considered equivocal (uncertain).
  • A result of 3+ is positive.

During an IHC test, pathologists analyze breast tissue under a 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 uncertain. Further testing will be required.

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 HER2 testing kits approved by the Food and Drug Administration (FDA).

Both IHC and ISH testing are 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 risk. 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.

Whether your results come back positive or negative, ask your doctor how confident they are in the lab that was used and in the results. Ask how many pathologists reviewed your sample.

If only one pathologist saw your 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 HER2 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.

You can also ask for a second opinion or ask to send your sample to a lab of your choice.

The good news is that HER2-targeted 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 your cancer and how to most effectively treat it. These tests should include a HER2 test.

Make sure you understand all the results before proceeding with treatment. If your breast cancer has returned after being treated, ask your doctor about the need to conduct a HER2 test.

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, treatments are very effective. Understanding your diagnosis and treatment options is important. Talk to your doctor to learn as much as you can.