HER2 / ERBB2 Biomarker
What is the HER2 biomarker?
The HER2 gene (also called ERBB2) is present in each of the cells in our body and is similar to the EGFR gene. The normal (wild type) HER2 gene contains the instruction for the HER2 protein (also called ERBB2 protein). The HER2 protein is present on the surface of almost all of the cells in our body and is responsible for the communication between the cells to promote their growth, division, movement and survival. When HER2 is active, the RAS/MAPK pathway is switched "on".
What does HER2 amplification mean?
In about 5% of all patients diagnosed with stage III or stage IV metastatic colorectal cancer (mCRC), the tumor contains too many copies of the HER2 gene and the HER2 protein. It is more common (up to 15% of tumors) in mCRC patients with wild type KRAS/NRAS or BRAF. HER2 gene amplification happens randomly as a somatic change only in the tumor cells. The condition is NOT hereditary (not a germline mutation) and will NOT pass from one generation to another. The overexpression of the HER2 protein in the cancer cells drives their uncontrolled growth.
HER2 amplification is more frequent in left-sided colon tumors than right-sided colon tumors.
When and how should I have a HER2 biomarker testing?
The National Comprehensive Cancer Network (NCCN) recommends HER2 biomarker testing in all patients diagnosed with stage IV metastatic colorectal cancer (mCRC) who have wild type KRAS, NRAS and BRAF proteins in their tumors. Patients with HER2 amplification/overexpression do not respond well to EGFR inhibitors. Therefore, HER2 testing should be done before starting treatments with EGFR inhibitors such as cetuximab or panitumumab.
Your doctor may also recommend re-testing the tumor for new or additional mutations and alterations when a chemotherapy treatment stops working and/or the stage IV tumor starts to grow again.
What do I do with this information?
Knowing the details of tumor biomarkers can help you and your doctor make decisions about personalized treatment with therapies tailored specifically to the characteristics of your tumor.
- HER2 amplification and overexpression is a predictive biomarker for poor response to treatment with EGFR inhibitors.
What treatment options are available?
Colorectal cancer with HER2 amplification or overexpression should be treated with dual-targeted therapy against HER2 with the combination of trastuzumab with either pertuzumab or lapatinib alone or with chemotherapy.
What are the potential side effects of immunotherapy?
Every treatment has the potential to cause some side effects. Some people may be more sensitive than others to a particular drug. It also depends on your other treatments, medications, vitamins and herbal supplements. For example, side effects could be worse if you are treated with radiation at the same time. Tell your doctor and pharmacist about all of your medications, vitamins, and treatments.
Some of the most common side effects associated with HER2 inhibitors are feeling or being sick, skin problems, headache and dizziness, fatigue, diarrhea or constipation, joint or muscle pain, and anemia/low hemoglobin levels. It is unlikely that you will have all of these side effects but you might have some of them. Call your doctor immediately if you are experiencing severe symptoms.
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