HER2—also sometimes referred to as HER-2 or Her-2/neu or erb-b2—is one of more than 100,000 genes found in the nucleus of all human cells. The HER2 gene helps cells grow, divide, and repair themselves. Every cell should have only two copies of the HER2 gene. If it has more than two copies (referred to as gene amplification), these extra genes result in there being too many HER2 protein receptors on the cancer cell’s surface (referred to as protein overexpression.) These receptors pick up more grow-and-divide messages than a cell should normally get, fueling the cancer’s growth.
About one in five women with breast cancer will have a tumor that is HER2+. HER2+ tumors appear to be more common among younger women than older women. They are called HER2+ because they have too many copies of the HER2 gene and too many HER2 receptors. These cancers are referred to as HER2-positive and respond to HER2-targeted therapies.
Having your tumor tested to see if it is HER2-positive is important because it will guide your oncologist in determining the best treatment strategy for you. Women with early-stage breast cancer that is HER2-positive can be treated with trastuzumab (Herceptin). For women with metastatic HER2+ breast cancer, HER2-targeted therapies include pertuzumab (Perjeta), lapatinib (Tykerb), and trastuzumab emtansine (Kadcyla). HER2 status is also an indicator of which types of chemotherapy a tumor is most likely to respond to. You can learn more about these treatments here.
There are two tests that a pathologist can use to determine if a tumor is HER2-positive. One, immunohistochemistry (IHC), assesses the overexpression of the HER2 protein; the other test, fluorescence in situ hybridization (FISH), assesses whether there are too many copies of the actual gene. It is the difference between measuring the effect (too much protein) or the cause (too many copies of the gene).
On the IHC test, a result of zero or 1+ means the tumor is HER2-negative; a result of 3+ means the tumor should be categorized as HER2-positive. If the result is 2+ on the IHC test, the tumor is borderline and the tissue should be retested with the FISH test. A FISH score greater than 2 means the tumor is HER2-positive.
When you find out information about your tumor, ask your doctor whether IHC, FISH, or both were used to determine your HER2 status. Because FISH is more difficult and more expensive to do, the current practice in the U.S. is to screen tumor samples with the IHC test. But the FISH test is actually more accurate. For this reason, any tumor that tests 2+ on IHC should be retested with FISH. If IHC was used and your test result is 2+, you should request a FISH test, if it has not already been done.
HER2 is an acquired mutation. It is not an inherited mutation, like BRCA1 or BRCA2 This means it is not a mutation that you could have inherited from a parent or passed on to your own child.