Lung Cancer
Molecular Testing & Biomarkers
Molecular testing has revolutionized how lung cancer is treated. These tests, which are typically performed during the diagnostic process, allow doctors to determine which genetic abnormalities may be causing or contributing to your disease. Much of the success of treating non-small cell lung cancer (NSCLC) is due to treatments designed to target specific abnormalities. Research is still focused on identifying new ones and ways to treat them.
We now understand that cancer arises from changes that occur in a person’s genes. These changes are known as mutations or genetic abnormalities, and they can cause cells to grow out of control and become cancer cells. Knowing the mutations involved can help your doctor diagnose your type or subtype of cancer, choose a treatment option designed for a specific mutation and monitor your condition for a possible recurrence.
A mutation is any change in the DNA sequence of a cell. Mutations may be caused by mistakes during cell division, or they may be caused by exposure to DNA-damaging agents in the environment. Some of these mutations may be detected in a tissue or blood sample (liquid biopsy). Several gene mutations that
are known to cause cancer have been discovered in lung cancer (see Table 1). The majority of lung cancer mutations have been found in NSCLC, but a new biomarker has been discovered in small cell lung cancer (SCLC). All stages of NSCLC (except Stage I) should have molecular testing because systemic therapy will be used in addition to surgery (or radiation therapy) either before (neoadjuvant) or after (adjuvant), or before and after surgery.
To determine whether your lung cancer has these mutations, your doctor should order biomarker testing on a tissue sample collected during a biopsy and on a peripheral blood sample. Not all cancer centers offer molecular testing, but samples can be sent to a commercial lab, so it is important to ask whether it has been performed on your blood or tissue samples. Ask your doctor to explain the biomarkers
you were tested for and the results.
If the testing has not been performed, request it to find out whether you may have access to drug therapies that target the cancer. Knowing your lung cancer’s biomarkers will be crucial to the development of your treatment plan and will help you take a more active role in your care.
How Samples are Tested
Some cancer centers only test for one or two biomarkers, but comprehensive biomarker testing allows your doctor to look for all possible alterations regardless of whether drugs have been approved for them or not.
Tissue testing is most commonly used for these tests and frequently requires 2 to 3 weeks to obtain the final results. It may be difficult to wait for results, but it is valuable to determine whether you have any mutations for which therapy is available. One biomarker your doctor may test for is PD-L1, which may indicate whether immunotherapy is right for you. It is not a biomarker for cancer, but used to determine if immunotherapy is an appropriate treatment.
Blood sample results often come back within a week and are accurate enough for therapy selection. They are not as sensitive as tissue testing, so waiting for the tissue results is standard unless there is a need for immediate therapy.
How Testing Impacts Treatment Choices
When testing confirms the presence of genetic abnormalities, depending on the mutation, you may be eligible for treatments such as molecular therapy, targeted therapy or immunotherapy. These treatments are designed to target only the specific genetic abnormalities causing cancer and may spare you from aggressive treatments such as chemotherapy, which can damage healthy cells and result in many side effects.
Biomarker testing may also be used during treatment to look for resistance to these therapies, or may be used if the cancer returns (recurrence). Resistance can occur when cancer cells – even a small group of
cells within a tumor – contain molecular changes that make them insensitive to a particular drug before treatment even begins. Because cancer cells within the same tumor often have a variety of molecular
changes, this so-called intrinsic resistance is common. Cancer cells can also adapt to the drug while it is being administered. These cancer cells acquire new molecular changes that allow them to escape the drug’s effects.
During treatment, it is important to monitor a patient for resistance because when cancer cells resist the effects of drugs, they can grow and reform tumors, a process known as recurrence or relapse. Sometimes resistance develops quickly, within a matter of weeks of starting treatment. In other cases, it develops months, or even years, later. When a tumor returns, it may have different genetic alterations than before, which may affect treatment options and prompt another round of biomarker testing to determine whether there is a new actionable genetic alteration for which a molecular therapy is available.
The results of the molecular testing will be given to your doctor in a pathology report. The format of the report may be different for each facility but generally includes details about your health history and results of the examination and laboratory testing of tissue and blood samples.
Sign Up for the Online Portal
Online portals offer a convenient way for you and your doctor to communicate outside of an office visit. The portal is a secure website that gives patients 24-hour access to personal health information. Most health care systems, hospitals and doctor’s offices have a patient portal. This portal helps patients to take a more active role in managing their health. Using a secure username and password, patients can view health information such as their lab results. Portals are often used in combination with your electronic health record, which contains all of your personal health history, including past diagnoses, medications and test results.
Many portals allow patients to securely message the doctor, request prescription refills, schedule non-urgent appointments, update contact information, download and complete forms, receive email reminders and alerts and other options. The portal allows you to be in touch with your health care provider’s office 24 hours a day, but they are not for urgent issues.
When you first meet your health care team, ask them if they offer an online patient portal. They will provide you with instructions for setting it up. You will create a username and secure password so that only you have access to your health information. Patient portals have privacy and security safeguards in place to protect your health information.
It is possible that your test results may be posted to the portal before your doctor has had a chance to explain them to you. The information may look confusing and you may not understand what the results mean. If you have any questions before the next appointment to go over the results and what they mean, it may be helpful to message the doctor through the online portal.
An online portal is a valuable tool to keep you connected with your health care team.
Step-by-Step
In general, your doctor will follow these steps:
- A biopsy of tumor tissue is taken. It can be done by several methods, and different tests require different amounts of tissue.
- The sample is sent to a laboratory where a pathologist looks for the presence of cancer cells and documents certain characteristics of the tumor cells in the sample.
- Specialized equipment is used to sequence the tumor’s DNA and find any abnormalities.
- If abnormalities are found, they are compared to known mutations of the type or subtype of your particular cancer.
- Results are returned to your doctor in a pathology report.
- If testing finds a genetic alteration, your doctor may suggest options that are approved to target that alteration.
- If the genetic alteration found does not have a specialized treatment, your doctor may recommend standard of care treatment or a clinical trial that is testing the mutation identified in your tissue sample.
Talk with your doctor about when and how you will receive results.
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
DLL3 |
| Optional biomarkers for immunotherapy | Microsatellite instability-high (MSI-H) or deficient mismatch repair (dMMR); tumor mutational burden (TMB) |
