What Is HER2 FISH Testing for Breast Cancer?

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.

Typically, HER2 proteins regulate and control the growth of breast cells. But when there’s a HER2 gene mutation, it makes too many HER2 proteins. According to the American Cancer Society (ACS), this protein overproduction occurs in about 15–20% of cases of breast cancer and 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. 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, finding out whether your cancer is HER2-positive or HER2-negative is a priority. It’s important to have the tests that determine this when your healthcare professional orders them for you. The results play a significant part 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. The test results 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 whether breast cancer cells have too many HER2 protein receptors. Using clinical guidance, the following is how a healthcare professional will interpret your test results:

• 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.

Some breast cancers that have an IHC result of 1+ or an IHC result of 2+ along with a negative FISH test might be called HER2-low cancers.

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 cancer’s HER2 status, your doctor will order a breast tissue biopsy. In most cases, the healthcare professional conducting the biopsy will use a local anesthetic to minimize pain. This tissue will be sent to a 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 is 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.

Do not 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.

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.

Enhertu is one drug that has recently been approved to treat HER2-low breast cancers that cannot be surgically or that have spread (metastasized) elsewhere in the body.

Below are some commonly asked questions about the HER2 FISH test.

What is a HER2 FISH test?

A HER2 FISH (Fluorescence In Situ Hybridization) test is done on breast cancer tissue removed during biopsy to see whether the cells have extra copies of the HER2 gene. If it reveals higher than normal levels of HER2, this indicates that a person has HER2-positive breast cancer.

What does a positive FISH test indicate?

A FISH test that produces a positive result indicates that a person has HER2-positive breast cancer.

How long does a FISH test for breast cancer take?

FISH tests may take roughly 1 week to generate a result. However, the hospital’s schedule and other factors may delay this.

What does it mean when HER2 is positive?

HER2 is a protein that helps breast cancer cells grow quickly. When breast cancer cells have higher than normal levels of HER2, this is known as HER2-positive.

If you’ve recently received a breast cancer diagnosis, 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.

When breast cancers return, their HER2 status may change. For example, what was once HER2-negative may be HER2-positive during a second diagnosis.

If a cancer is diagnosed as HER2-positive, treatments are very effective. Understanding your cancer diagnosis and treatment options is important. Talk with your doctor to learn as much as you can.