HER2 Biomarker

HER2 is both a prognostic and a predictive biomarker in colorectal cancer. The HER2 gene (which may also be referred to as ERBB2) encodes the HER2 protein which functions as a receptor on the cell surface. The receptor receives signals and communicates to promote cell growth, division, and survival.  

If your tumor is HER2-negative, your tumor has normal levels of HER2 protein expression.   

If your tumor is HER2-positive, your tumor has abnormal, or elevated, levels of HER2 protein expression. This can be a result of tumors containing too many copies, or amplification, of the HER2 gene. When the HER2 gene is amplified, there is an overproduction of HER2 protein. However, there are other causes (such as epigenetic changes) that result in overexpression of the HER2 protein. The overexpression of HER2 receptors on tumor cells results in too many signals telling the cell to keep growth and dividing, leading to uncontrolled cell growth and division. 

HER2 is more well known for its role in breast cancer. However, HER2 plays a role in several solid tumors, including breast cancers, gastric cancers, and colorectal cancers. 

Patients who are KRAS, NRAS and BRAF wild-type should undergo HER2 biomarker testing.  

The most common method for testing HER2 status is using a tumor biopsy sample from the primary tumor. Alternatively, a blood sample using circulating tumor DNA (ctDNA), also called a liquid biopsy may be used. HER2 status may be tested individually or as part of a multi-gene panel. 

The best way to ensure your tumor has been tested for its HER2 status is to ask your medical care provider.    

A report for your tumor’s HER2 status will likely be reported as “HER2 positive” if there is gene amplification and/or protein overexpression or “HER2 negative” if there is no gene amplification and/or protein overexpression. HER2 positivity may include a number to indicate the amount of HER2 expressed in the tumor sample, with a higher number representing more HER2 expression. 

Approximately 3-5% of colorectal cancer tumors are HER2-positive, and HER2-positivity is more common in colorectal cancers that are KRAS, NRAS, and BRAF wild-type. HER2-positivity is more common in left-sided colon tumors than in right-sided colon tumors.  

If your tumor is HER2-negative, your tumor has normal levels of HER2 expression.   

• Treatment for HER-2 negative colorectal cancer tumors is often indicated by other biomarker testing results, tumor location, or tumor stage. These treatment options may include traditional chemotherapy, targeted therapies, and/or immunotherapies.  

If your tumor is HER2-positive, your tumor has abnormal, or elevated, levels of HER2 expression.  

• HER2-positive tumors are less likely to respond to EGFR inhibitors (also called anti-EGFR therapies) and they are not often recommended.
• HER2-positive tumors may respond to anti-HER2 therapies (also called HER2 inhibitors) alone or in combination with other treatment options.  The goal of HER2 inhibitors is to block the HER2 receptor from receiving signals and, as a result, slow or stop the growth of cancer cells.   

A HER2-positive CRC is often treated with HER2 inhibitors such as trastuzumab, pertuzumab, lapatinib, trastuzumab deruxtecan-nxki, or tucatinib. Treatment may include a combination of HER2 inhibitors or a HER2 inhibitor in combination with traditional chemotherapy.  

Lapatinib is a dual-targeted therapy: it is both a HER2 inhibitor and an EGFR inhibitor. Lapatinib may be an option for HER2-positive colorectal cancer and may be used in combination with another HER2 inhibitor.  

The most effective treatment varies by individual. It is best to speak with your medical team to learn more about the best treatment options for you. 

Drugs targeting HER2-positive colorectal cancer are being tested in clinical trials. Talk to your medical team to determine if you may benefit from a clinical trial and find a trial in our Clinical Trial Finder.