Genes contain the recipes for the various proteins a cell needs to stay healthy and function normally. Some genes and the proteins they make can influence how a breast cancer behaves and how it might respond to a specific treatment. Cancer cells from a tissue sample can be tested to see which genes are normal and abnormal. The proteins they make can also be tested.
HER2 (human epidermal growth factor receptor 2) is one such gene that can play a role in the development of breast cancer. Your pathology report should include information about HER2 status, which tells you whether or not HER2 is playing a role in the cancer.
The HER2 gene makes HER2 proteins. HER2 proteins are receptors on breast cells. Normally, HER2 receptors help control how a healthy breast cell grows, divides, and repairs itself. But in about 25% of breast cancers, the HER2 gene doesn't work correctly and makes too many copies of itself (known as HER2 gene amplification). All these extra HER2 genes tell breast cells to make too many HER2 receptors (HER2 protein overexpression). This makes breast cells grow and divide in an uncontrolled way.
Breast cancers with HER2 gene amplification or HER2 protein overexpression are called HER2-positive in the pathology report. HER2-positive breast cancers tend to grow faster and are more likely to spread and come back compared to HER2-negative breast cancers. But there are medicines specifically for HER2-positive breast cancers.
How your results appear in the report will depend on what test you have. There are four tests for HER2:
- IHC test (ImmunoHistoChemistry): The ImmunoHistoChemistry test finds out if there is too much HER2 protein in the cancer cells. The results of the IHC test can be: 0 (negative), 1+ (also negative), 2+ (borderline), or 3+ (positive — HER2 protein overexpression).
- FISH test (Fluorescence In Situ Hybridization): The Fluorescence In Situ Hybridization test finds out if there are too many copies of the HER2 gene in the cancer cells. The results of the FISH test can be positive (HER2 gene amplification) or negative (no HER2 gene amplification).
- SPoT-Light HER2 CISH test (Subtraction Probe Technology Chromogenic In Situ Hybridization): The SPoT-Light test finds out if there are too many copies of the HER2 gene in the cancer cells. The results of the SPoT-Light test can be positive (HER2 gene amplification) or negative (no HER2 gene amplification).
- Inform HER2 Dual ISH test (Inform Dual In Situ Hybridization): The Inform HER2 Dual ISH test finds out if there are too many copies of the HER2 gene in the cancer cells. The results of the Inform HER2 Dual ISH test can be positive (HER2 gene amplification) or negative (no HER2 gene amplification).
It's important to know which HER2 status test you had. Generally, only cancers that test IHC 3+, FISH positive, SPoT-Light HER2 CISH positive, or Inform HER2 Dual ISH positive respond to the medicines that target HER2-positive breast cancers. An IHC 2+ test result is called borderline. If you have an IHC 2+ result, ask to have the tissue retested with a more precise HER2 test: the FISH test, SPoT-Light HER2 CISH test, or the Inform HER2 Dual ISH test.
Research has shown that some breast cancers that are HER2-positive can become HER2-negative over time. Likewise, a HER2-negative breast cancer can become HER2-positive over time. If the breast cancer comes back in the future as advanced disease, doctors should consider ordering another biopsy and retest the tissue’s HER2 status.
HER2 testing accuracy
Research has shown that some HER2 status test results may be wrong. This is probably because different labs have different rules for classifying positive and negative HER2 status. Each pathologist also may use slightly different criteria to decide whether the results are positive or negative. In most cases, this happens when the test results are borderline — meaning they aren't strongly HER2-positive or HER2-negative.
In other cases, tissue from one area of a breast cancer can test HER2-positive and tissue from a different area of the cancer can test HER2-negative.
Inaccurate HER2 test results may cause women diagnosed with breast cancer to not get the best care possible. If all or part of a breast cancer is HER2-positive but test results classify it as HER2-negative, doctors aren't likely to recommend Herceptin or Tykerb treatment — even though the woman could potentially benefit from those medicines. If a breast cancer is HER2-negative but test results classify it as HER2-positive, doctors may recommend Herceptin or Tykerb treatment — even though the woman is unlikely to get any benefits and is exposed to the medicines' risks.
If your HER2 test results are HER2-negative, you may want to ask your doctor about how confident he or she is in the lab that did the HER2 testing and if another HER2 test might make sense for your unique situation.
If your HER2 test results are borderline, it's a good idea to ask if another HER2 test makes sense for you.
Treatments for HER2-positive breast cancer
There are some treatments available specifically for HER2-positive breast cancer. The most commonly used medication is Herceptin (chemical name: trastuzumab), which works by attaching itself to the HER2 receptors on breast cancer cells and blocking them from receiving growth signals. By blocking these signals, Herceptin may help to slow or even stop the growth of the breast cancer. In addition to blocking HER2 receptors, Herceptin can also help fight breast cancer by alerting the immune system to destroy cancer cells onto which it is attached.
Another option for some women with advanced HER2-positive breast cancer is Tykerb (chemical name: lapatinib). Tykerb works by interfering with certain proteins that cause the cell to grow and divide abnormally. Tykerb can be used:
- in combination with Xeloda (chemical name: capecitabine), a type of chemotherapy, to treat advanced, HER2-positive breast cancer that has stopped responding to other forms of chemotherapy known as anthracyclines and taxanes, and to Herceptin
- in combination with Femara (chemical name: letrozole), a type of hormonal therapy, to treat postmenopausal women diagnosed with hormone-receptor-positive, HER2-positive advanced-stage breast cancer