Determining Your HER2 Status

Patient Expert

If you have been diagnosed with breast cancer, you probably have seen a pathology report referring to your HER2 status. New research may affect how your doctor interprets your HER2 status, and the drugs you receive.

What is HER2?

HER2 (human epidermal growth factor receptor) is one of many proteins involved in cell division. The surface of cells have receptors to capture this protein and send it into the cell to tell the nucleus to divide. There are many stages in this process, and if something goes wrong at any point, cell growth is affected.

Cancer is a disease of wild cell division. Instead of cells dividing, growing, and dying in a well-regulated way, they multiply out of control. This can happen for many reasons. One is that a person’s cells have too many HER2 receptors on the surface, making the cells multiply too fast. Sometimes this is called HER2 overexpression or amplification.

For a long time, doctors knew that having too many HER2 receptors made a cancer tumor more aggressive, but they didn’t have a way to treat HER2-positive tumors. Chemotherapy attacks all rapidly growing cells, and can be a blunt instrument. During the 1990s, a new type of therapy was developed that targeted the HER2 receptors. Herceptin was the first of these “targeted therapies” to be FDA approved for breast cancer.

What if the HER2 status is not clear?

Determining whether a tumor is a HER2 over expressor can be difficult. Immunohistochemistry (IHC) is usually the first test used to determine HER2 status. If the score on it is “equivocal” (unclear), then the fluorescent in situ hybridization (FISH) test, is ordered because it is more precise. In a study at the Mayo Clinic that combined these with a third test, researchers were able to identify patients who might benefit from targeted therapies and would otherwise have been considered ineligible.

The Mayo scientists analyzed HER2 results from 2,851 patients, most of whom had equivocal scores on the IHC test.  On the FISH test, 16 percent were positive, and 14 percent remained equivocal. Doing an alternative chromosome 17 probe on those who were still equivocal on the FISH test showed about half of this group to be HER2 positive.

Deciding how to score test results is a work in progress. The Mayo researchers also looked at how a change in guidelines from 2007 to 2013 affected the number of patients who were considered HER2 positive. Under new guidelines another 11 percent to 13 percent would be considered positive compared to the 2007 guidelines.

Should you check with your doctor?

If you were diagnosed before 2013, when the new guidelines were adopted, or if you had a borderline HER2 score, talking to your doctor might be a good idea. Additional testing with the alternative chromosome 17 probe method could clarify your status. You might be eligible for a targeted therapy such as Herceptin.

Could your HER2 status change?

If you have completed treatment and are doing fine, there is no reason to worry. But if you have a recurrence, you should not assume that your hormone and HER2 status remain the same. Tumors are made up of a mixture of types of cells. Let’s say that in your original pathology report, most of the cells were sensitive to estrogen and only a few showed overexpression of HER2. Your pathology report would say that you were ER positive and HER2 negative. Your doctor gave you treatments that killed the ER positive cells, but that might have been ineffective against the minority of HER2, allowing them to grow and become the majority of cells in the new tumor. Now you need a targeted therapy.

Researchers at Massachusetts General Hospital found that HER2 status can even flip spontaneously from negative to positive. They are not yet certain why, but this work points out the importance of asking for a new assessment of your HER2 status if your cancer treatment is not working or if you have had a recurrence.

Knowing your HER2 status and how it was determined is one important part of understanding your cancer and making decisions about the best way to treat it.

See More Helpful Articles:

FAQS: HER2-neu

Is Your Pathology Report Correct? When to Ask for a Second Opinon

Reading the Pathology Report: A Layperson’s Guide to Understanding Your Breast Cancer Diagnosis

Phyllis Johnson is an inflammatory breast cancer survivor who serves on the Board of Directors for the Inflammatory Breast Cancer Research Foundation, the oldest 501(3)(c) organization focused on research for IBC. She is a list monitor for an online support group at She stays current on cancer information through attendance at conferences such as the National Breast Cancer Coalition’s Project LEAD® Institute. A retired teacher, she has been writing about cancer issues at HealthCentral since 2007.