HER2 / ERBB2 Biomarker

The HER2 or ERBB2 gene (human epidermal growth factor receptor-2) is in each of the cells in our body and is in the same family as the EGFR gene. The HER2 protein is a receptor on the surface of almost all the cells in our body. It is responsible for the communication between the cells to promote their growth, division, repair, and survival.

Approximately 3-4% of colorectal cancer tumors contain too many copies of the HER2 gene and the HER2 receptor. This is known as amplification. It is more common (6-8%) in CRC patients with wild type KRAS. HER2 gene amplification happens randomly as a somatic change only in the tumor cells. The condition is NOT hereditary (germline mutation) and will NOT pass from one generation to another. When the gene is amplified, it produces excess receptors on the tumor cells and drives uncontrolled growth.

HER2 amplification is more frequent in left-sided colon tumors than right-sided colon tumors.

The National Comprehensive Cancer Network (NCCN) recommends HER2 biomarker testing in all patients diagnosed with stage IV, metastatic colorectal cancer (mCRC). Patients with HER2 amplification/overexpression do not respond well to EGFR inhibitors. HER2 testing should be done before starting treatments with EGFR inhibitors such as cetuximab or panitumumab.

If you have a recurrence or new metastatic disease, your doctor may recommend testing the new tumors to help direct your treatment.

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.

Colorectal tumors that have HER2 amplification and overexpression and are RAS and BRAF wild type should be treated with dual-targeted therapy against HER2 with the combination of trastuzumab with either pertuzumab or lapatinib alone or with chemotherapy.

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.