In short
Understanding how HER2 mutant non-small cell lung cancer is diagnosed can feel overwhelming, especially when facing an unexpected diagnosis. Testing for this specific mutation is a crucial first step that helps doctors determine the best treatment path, and knowing when and how this testing happens can help you feel more prepared and in control.
Key points
- HER2 mutations occur in about 2 to 4 percent of non-small cell lung cancer cases and are more common in women, never-smokers, and people of Asian descent, though testing is recommended for all advanced lung cancer patients.
- Comprehensive genetic testing using next-generation sequencing should be performed as soon as lung cancer is diagnosed to identify HER2 and other important mutations that can guide treatment choices.
- Both tissue biopsies and liquid biopsies can detect HER2 mutations, with many centers now using both methods simultaneously to speed up diagnosis and avoid missing important genetic changes.
- Two FDA-approved diagnostic tests exist specifically for detecting HER2 mutations in lung cancer: Guardant360 CDx using blood samples and Oncomine Dx Target Test using tumor tissue.
- HER2 testing in lung cancer looks for specific gene mutations, particularly in exon 20, which is different from the HER2 protein overexpression testing done in breast cancer.
- Clinical trial participation often requires additional diagnostic tests beyond standard workup, including detailed imaging, blood work to assess organ function, and sometimes brain MRI scans.
- HER2 mutant lung cancer has a higher tendency to spread to the brain compared to some other types, making brain imaging an important part of the diagnostic evaluation.
- Test results should clearly indicate whether a HER2 mutation is pathogenic and targetable, helping doctors quickly develop an appropriate treatment plan tailored to your specific cancer type.
Introduction: Who Should Undergo Diagnostics and When
If you have been diagnosed with non-small cell lung cancer, or if doctors suspect you might have this condition, testing for HER2 mutations—which are changes in a specific gene that can drive cancer growth—is an important part of understanding your disease. HER2 is a protein that naturally exists on the surface of cells, but mutations in the HER2 gene can cause abnormal cell activity that promotes cancer growth. These mutations occur in about 2 to 4 percent of people with non-small cell lung cancer.
People who should undergo diagnostic testing for HER2 mutations are those who have been diagnosed with advanced non-small cell lung cancer, particularly if the cancer cannot be removed by surgery or has spread to other parts of the body. This kind of testing is especially important for patients who have nonsquamous non-small cell lung cancer, which is the type that does not involve flat, scale-like cells in the lung lining. All patients with advanced non-small cell lung cancer should receive biomarker testing, which is a type of genetic testing that looks for specific mutations in your cancer that can be targeted with certain treatments.
Certain groups of people are more likely to have HER2 mutations in their lung tumors. Research shows that women, people who have never smoked or are light smokers, and those of Asian descent are more likely to carry this mutation. However, this does not mean that only these groups should be tested. Every patient with advanced non-small cell lung cancer should receive comprehensive testing regardless of their smoking history or other characteristics, because identifying a HER2 mutation opens up specific treatment options that might not otherwise be available.
Testing should happen as soon as possible after diagnosis. When lung cancer is first detected and confirmed through imaging tests and biopsies, the next critical step is to perform detailed genetic testing on the tumor tissue or blood to look for mutations like HER2, along with other important genetic changes such as those in the EGFR, ALK, and BRAF genes. This comprehensive approach ensures that your treatment plan is tailored to the specific characteristics of your cancer.
Diagnostic Methods
Diagnosing HER2 mutant non-small cell lung cancer involves several types of tests that work together to give doctors a complete picture of your condition. The process typically begins with standard cancer detection methods, followed by more specialized genetic testing to identify specific mutations.
Initial Cancer Detection
The journey to diagnosis often starts when symptoms like a persistent cough, chest pressure, fatigue, or weight loss prompt a visit to a healthcare provider. When lung cancer is suspected, doctors typically begin with imaging tests such as chest X-rays, which can reveal abnormalities in the lungs. If the X-ray shows something concerning, such as fluid buildup or masses, more detailed imaging is ordered.
CT scans (computed tomography scans) are three-dimensional images that provide a much more detailed view of the lungs and can help identify tumors, fluid accumulation, or other abnormalities. These scans are essential for determining the extent of the disease and whether cancer has spread to other parts of the body. Sometimes doctors may also use other advanced imaging techniques like PET scans or MRI scans to get additional information about the cancer's location and spread.
Once imaging reveals suspicious areas, a biopsy is performed to confirm the presence of cancer. A biopsy involves removing a small sample of tissue from the tumor so it can be examined under a microscope. This can be done in several ways depending on where the tumor is located. In some cases, a needle biopsy is performed by inserting a thin needle through the chest wall to collect tissue. In other situations, doctors may use a procedure called bronchoscopy, where a thin tube with a camera is passed through the airways to reach the tumor and collect samples.
Genetic Testing for HER2 Mutations
After cancer has been confirmed, the tumor tissue undergoes specialized genetic testing to look for mutations that can guide treatment decisions. This is where HER2 mutation testing comes in. The most comprehensive approach is to use next-generation sequencing, which is a type of genetic testing that can look for many different mutations at once using a single tissue sample. This panel testing is now considered standard care for people with advanced lung cancer because it identifies not just HER2 mutations but also other important genetic changes that might affect treatment choices.
There are two main FDA-approved companion diagnostic tests specifically for detecting HER2 gene mutations in lung cancer patients. The first is called Guardant360 CDx, which uses a blood sample to detect genetic changes. The second is the Oncomine Dx Target Test, which analyzes tumor tissue. Both tests are designed to accurately identify the presence of activating HER2 mutations, which are the specific types of genetic changes that drive cancer growth and can be targeted with certain medications.
The genetic testing can be performed on tumor tissue obtained from a biopsy, or it can be done using a blood sample in what is called a liquid biopsy. Liquid biopsies have become increasingly popular because they are less invasive and can be especially helpful when tumor tissue is difficult to obtain or when not enough tissue is available for comprehensive testing. Many cancer centers now perform both tissue and liquid biopsies at the same time to speed up the process and to catch any mutations that one method might miss.
The testing looks specifically for HER2 exon 20 mutations, which are the most common type of HER2 mutation found in lung cancer. An exon is a segment of a gene, and exon 20 mutations refer to changes in that particular segment of the HER2 gene that cause it to be constantly activated, leading to uncontrolled cancer cell growth. The most frequently identified mutation is a 12 base pair in-frame insertion in exon 20, which is found in the majority of HER2 mutant lung cancers.
Understanding Test Results and Reports
When your test results come back, the report should clearly indicate whether a HER2 mutation was found and what type of mutation it is. The report might also include information about other genetic changes detected in your cancer. It is important that the report labels the HER2 mutation as pathogenic, meaning it is disease-causing and can be targeted with specific therapies, rather than listing it as a variant of uncertain significance, which means doctors are not sure if it has any impact on the cancer.
The turnaround time for genetic testing results can vary, but many centers are working to provide results within one to two weeks. This timing is important because it allows your treatment team to quickly develop a plan that is tailored to your specific type of cancer. If there are any delays in getting tissue or if the tissue sample is not adequate for testing, a liquid biopsy can sometimes provide faster results.
Diagnostics for Clinical Trial Qualification
When patients with HER2 mutant non-small cell lung cancer are being considered for clinical trials, additional diagnostic tests and criteria are often required beyond the standard diagnostic workup. Clinical trials are research studies that test new treatments or new ways of using existing treatments, and they have specific entry requirements to ensure that the study results are reliable and that participants are likely to benefit.
For patients to qualify for HER2-targeted therapy clinical trials, they must first have confirmed HER2 mutations detected through approved diagnostic methods. Most clinical trials require that the HER2 mutation be identified using next-generation sequencing performed in a laboratory that meets certain quality standards. The trial protocols typically specify which types of HER2 mutations are eligible, with most focusing on HER2 exon 20 mutations, particularly insertion mutations.
Beyond confirming the presence of a HER2 mutation, clinical trials usually require documentation of the cancer stage and extent of disease spread. Patients generally need to have advanced or metastatic non-small cell lung cancer, meaning the cancer cannot be removed by surgery or has spread to other parts of the body. Imaging tests such as CT scans, PET scans, or MRI scans are used to document the extent of disease and establish baseline measurements of tumors before treatment begins.
Many clinical trials also require information about prior treatments. For example, some trials are designed specifically for patients who have already received one or more lines of therapy and whose cancer has progressed despite treatment. In these cases, documentation of previous chemotherapy, immunotherapy, or other treatments is needed. Other trials might focus on patients who have not yet received any systemic treatment for their advanced cancer.
Performance status is another important qualification criterion for clinical trials. Doctors assess how well you are able to carry out daily activities using standardized scales. This helps determine whether you are healthy enough to participate in the trial and tolerate the study treatment. Most trials require that participants be relatively functional and able to care for themselves with minimal assistance.
Blood tests are routinely required as part of clinical trial screening. These tests evaluate organ function, particularly the heart, liver, and kidneys, and check blood cell counts to ensure that your body can handle the study treatment. Specific tests might include complete blood counts, liver function tests, kidney function tests, and sometimes heart function assessments using echocardiograms, which are ultrasound images of the heart.
For trials testing HER2-targeted therapies, some require confirmation that the tumor does not have other common mutations that would make different targeted therapies more appropriate. For example, if a patient has both an EGFR mutation and a HER2 mutation, the trial might exclude them because EGFR-targeted therapy would typically be the preferred first choice. This ensures that the study specifically evaluates how well the HER2-targeted treatment works in patients for whom it is the most relevant option.
Brain imaging is often required for clinical trial qualification, particularly for HER2 mutant lung cancer, because this type of cancer has a higher tendency to spread to the brain compared to some other types of lung cancer. An MRI of the brain is typically performed to determine whether there are any brain metastases, and the presence or absence of brain involvement can affect which trials you are eligible for. Some trials specifically include patients with brain metastases, especially newer trials testing treatments that can penetrate the blood-brain barrier, while others might exclude patients with active brain disease.
The process of qualifying for a clinical trial can take time because it involves gathering all of the required test results and medical records, and sometimes repeating certain tests if previous results are outdated. Your healthcare team will guide you through this process and help ensure that all necessary documentation is collected and submitted according to the trial requirements.
