Lung Cancer
Biomarker Testing
After imaging studies are used to begin the diagnostic and staging process, biomarker testing may be performed on a blood or biopsy sample or metastatic site. A pathologist, a doctor who has special training in identifying diseases by studying cells and tissues under a microscope, will perform these tests in a laboratory. The goal is to identify characteristics of the tumor or to find changes in the DNA or cell surface proteins that may be used to offer more personalized treatment options, such as targeted therapy or immunotherapy.
Biomarker testing is recommended for all people diagnosed with non-small cell lung cancer (NSCLC), but it is considered necessary for adenocarcinomas. The goal is to find mutations that have treatments approved for NSCLC. Mutations in the ALK and EGFR genes are the most common in NSCLC that also have approved treatments. For small cell lung cancer (SCLC), no targeted therapies are approved, so biomarker testing will determine whether immunotherapy is an option.
Biomarker Testing
This type of testing looks for mutations (abnormal changes) in the DNA of your cancer cells. It is typically performed as part of the diagnostic process. Biomarker testing is used to determine whether lung cancer has certain gene mutations that can be targeted by specific treatments. These mutations can be detected as biomarkers, which are biological molecules found in blood or other body fluids or tissues. For NSCLC, it is preferred to use a tumor sample for biomarker testing. Blood can also be used, especially if there is not a large enough tissue sample to complete the testing.
Research has uncovered multiple genes with mutations that contribute to the development of lung cancer. Some mutations in NSCLC have specific treatments approved to treat them (see Table 1.)
Not all mutations have an approved therapy option available, but comprehensive biomarker testing allows the pathologist to look for all possible mutations regardless of whether drugs have been approved for them or not. Research in clinical trials is ongoing to find and develop more targeted treatments.
Some biomarkers are tested to determine eligibility for immunotherapy. Everyone with lung cancer should be tested for a biomarker known as programmed death-ligand 1 (PD-L1). Some cancer cells have an excessive amount of PD-L1 on their surface. Testing will reveal whether you have a high level of PD-L1, which may indicate that you may be more likely to respond to certain types of immunotherapy.
Other biomarkers may be tested for immunotherapy eligibility or to predict treatment response. These are not standard tests.
- Microsatellite instability-high (MSI-H) or deficient mismatch repair (dMMR) . If diagnostic tests determine that your lung cancer is MSI-H or has dMMR, it means the cancer cells may have a defect in the ability to correct mistakes that occur when DNA is copied in the cell. These mutations may qualify you for treatment with some types of immunotherapy.
- Tumor mutational burden (TMB) . TMB is an assessment of the number of genetic mutations in a tumor. It is believed that the higher the TMB level, the more likely you are to respond to immunotherapy. When there are 10 or more mutations per million base pairs in a tumor’s DNA, it is called tumor mutational burden-high (TMB-H). This biomarker can help predict a response to immunotherapy.
Delta-like ligand 3 (DLL3) . DLL3 is a protein that is highly expressed on SCLC cells but not healthy cells. Because most SCLC cells have DLL3, this test is not required for a person to qualify for the immunotherapy approved to treat SCLC. However, it may be used to qualify you for a clinical trial investigating other novel therapies, which may include DLL3-targeted therapies.
Tissue testing frequently requires a wait of two to three weeks to receive the results. Blood sample (liquid biopsy) results often come back within a week and are accurate enough for your doctor to select a therapy.
Types of Tests
Several types of biomarker testing can be done to help determine the best treatment options for your cancer.
- Immunohistochemistry uses antibodies to check for certain markers in a sample of tissue. The antibodies are usually linked to an enzyme or a fluorescent dye to see the antibody under a microscope. It is primarily used to determine the status of the tumor’s human epidermal growth factor receptor-2 (HER2) status or PD-L1 levels.
- Next-generation sequencing (NGS) is a high-throughput method used to determine the DNA sequence or gene changes of cancer cells in the tumor. This method will only be used if enough tumor tissue remains after initial pathologic assessment has been completed. In some cases, testing can use up a tumor sample and a liquid biopsy may be an option.
- Liquid biopsy
is a laboratory test done on a sample, typically of blood (sometimes urine or other body fluid), to look for cancer cells from a tumor or small pieces of DNA or other molecules released by tumor cells into a person’s bodily fluids. A liquid biopsy for blood will involve having blood drawn that may be used for multiple purposes:
- Personalized treatment planning
- Treatment monitoring
- Recurrence monitoring/finding
Table 1.
Some Common Biomarkers In Lung Cancer
| Description | Type |
| Gene mutations |
BRAF
EGFR ERBB2 (HER2) KRAS MET |
| Gene fusions |
ALK
NTRK RET ROS1 |
| Biomarkers for immunotherapy | PD-L1
|
| Optional biomarkers for immunotherapy | Microsatellite instability-high (MSI-H) or deficient mismatch repair (dMMR); tumor mutational burden (TMB) |
