Genetic Testing for HER2-Negative Breast Cancer

Medically Reviewed by Gabriela Pichardo, MD on June 12, 2022
Written by Julie Marks
3 min read

HER2 stands for “human epidermal growth factor receptor 2.” It's a gene in your body that creates proteins that promote cancer cell growth.

Normally, HER2 helps breast cells grow, divide, and repair themselves. But in about 10% to 20% of breast cancers, the HER2 gene doesn’t work as it should and makes too many copies of itself.

HER2-positive breast cancers are often more aggressive. They may need a different treatment approach than HER2-negative cancers.

HER2 gene defects, known as “mutations,” develop sometime during your life. Researchers aren’t sure exactly what causes these mistakes to happen.

There are other kinds of mutations linked to breast cancer that you can inherit from your parents. If this happens, it doesn’t mean you’ll definitely develop breast cancer. But your chances of developing the disease are higher.

Hereditary breast cancer only makes up about 5% to 10% of cases. You can find out if you have a hereditary form of breast cancer with genetic testing.

Researchers have identified more than 110 genes associated with breast cancer. Some of the most well-known of these are BRCA1, BRCA2, and PALB2.

People with HER2-positive breast cancer rarely have a mutation in the BRCA1 or BRCA2 genes.

Doctors will typically look for a HER2 defect with a biopsy, which is a procedure to remove and test a sample of tumor tissue. 

The two main types of tests used to detect breast cancer HER2 status are:

  • Immunohistochemistry assay (IHC). This test uses a chemical dye to stain the HER2 proteins. It measures the amount of these proteins on the surface of the cells.
  • Fluorescence in situ hybridization test (FISH). With a FISH test, special labels with chemicals added to them change color and glow in the dark when they attach to HER2 proteins. It looks for extra copies of the HER2 gene. 

The FISH test is the most accurate. But it’s also the most expensive, and it takes a while to get your results. For these reasons, your doctor might first suggest that you have an IHC test.

Breast cancers with high levels of the HER2 protein are HER2-positive, and those with low levels of the HER2 protein are HER2-negative.

This generally means:

  • If your IHC score is 0 to 1+, your cancer is HER2-negative.
  • If your IHC score is 3+, your cancer is HER2-positive.
  • If your IHC score is 2+, your cancer is “borderline.” Your doctor will probably recommend that you have the FISH test.
  • If your FISH score is positive, your cancer is HER2-positive.

What’s tricky is that some breast cancers labeled HER2-positive can become HER2-negative over time. And HER2-negative breast cancer can switch to HER2-positive.

Researchers have found that sometimes HER2 test results are wrong. This can happen because pathologists who examine the samples use different lab processes to classify the tissue. Or tissue from one area of the breast may test positive, while tissue from another area can test negative.

You may want to talk to your doctor about the accuracy of your test results. If they’re borderline, your doctor might recommend another test.

It’s important to know your HER2 status because doctors often recommend different therapies for HER2-positive breast cancer and HER2-negative breast cancer.

For instance, doctors treat many HER2-positive cancers with the medicine trastuzumab (Herceptin), which attaches to extra HER2 proteins and stops cancer growth.

Experts recommend that all people with invasive breast cancer be tested for HER2. Routine testing usually isn’t done for a noninvasive type of breast cancer called ductal carcinoma in situ.

If your breast cancer returns or spreads, your doctor may retest the cells for HER2 abnormalities because results can change.

If you have breast cancer and don’t know your HER2 status, talk to your doctor.