Comprehensive Biomarker Testing for Lung Cancer: Who Needs It & What’s It For?

“Comprehensive biomarker testing is critically important in lung cancer,” Nicholas Rohs, MD, a hematologist-oncologist at Mount Sinai Hospital in New York City, tells SurvivorNet, “It makes a huge difference in how we manage patients and definitely gets them the best care.”

Biomarker Testing – At a Glance

• Comprehensive biomarker testing checks the lung tumor for gene mutations that might respond to targeted therapy.
• Genetic testing of the lung tumor is typically for people with stage 4, non-small cell lung cancer. However, biomarker testing is becoming increasingly common for patients with lung cancer at any stage.
• If your doctor does not mention it, ask for it! Be your own advocate.

Biomarkers – What You Need to Know

Before we plunge into the details of biomarker testing or how it works for patients, let’s quickly understand what a biomarker is. Biomarker typically refers to a molecule doctors can measure in bodily fluids, tissues, and/or blood. Your blood has several different biomarkers. Some of them indicate  a normal bodily condition or a process, while others may suggest a disease or an abnormal process.

“The purpose of precision medicine is to identify a specific target, a specific biomarker, that allows us to select specific treatment,” said Dr. Ronald Natale, director of the Lung Cancer Clinical Research Program at the Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center in Los Angeles, in a previous interview with SurvivorNet.

In the medical field, it may also be referred to as a genotype, molecular marker, or signature molecule. Biomarkers can determine the following:

• Whether a patient has a disease
• The way a normal or abnormal process is functioning in the body
• The type or nature of a disease
• How well a patient’s body will react or respond to a treatment

As mentioned, comprehensive biomarker testing is one-way healthcare specialists can collect information about the unique type of lung cancer in the patient. The healthcare team performs biomarker testing prior to treatment to ensure the treatment will be effective. Moreover, the results of comprehensive biomarker testing determine whether certain FDA-approved targeted therapies or a specific immunotherapy medication for lung cancer is the best treatment option. Comprehensive biomarker testing is used to create a viable treatment plan for patients with lung cancer, including the advanced stages.

How it Works – Understanding Protein Production

To understand how comprehensive biomarker testing works, you must know about the cancer cell survival in the body. When there is a gene mutation in a cancerous tumor, it produces proteins in the cancer cells. This protein production on the surface of the cells leads tumors to breed and thrive. It is worth noting that gene mutation has many types, and each type produces different associated proteins. For example, EGFR protein can drive the growth of tumors in one patient, while in another patient, it may be the ROS1 protein that does so.

Healthcare teams use targeted therapies to detect and attack the particular protein contributing to the survival of the unwanted cancerous cells. Physicians use different drugs to target the certain protein production a cancer patient’s tumor possesses. Comprehensive biomarker testing plays a vital role in the detection of said specific protein production. Biomarker testing is an effective way to test a tumor in the lungs or determine if a targeted anti-cancer drug may be beneficial.

In essence, the test is comprehensive as it checks for a variety of mutations that FDA-approved drugs may target. Keep in mind that not all tumors carry mutations. In most cases, tumors have a single actionable mutation (multiple mutations are rare but possible). “I have occasionally seen two co-mutations,” says Rohs, “But, it’s so rare that it might tell me the patient actually has two different primary cancers. So, if that pops up, it leads to a lot of questions.” For a biomarker to be tested, there is the need for a sample of the tumor. This process is called a “biopsy.”  Tumor tissues can be obtained by using a variety of biopsy techniques and most of them are minimally-invasive.

Who Needs Biomarker Testing?

It is worth mentioning that patients with stage 4 metastatic lung cancer are the majority of patients who receive targeted therapies. However, many clinical studies are ongoing that explore the efficacy of targeted therapies for patients in earlier stages, like stage 2 or 3. Some published studies have shown that EGFR inhibitors are effective for stage 2 and 3 lung cancer. A bulk of evidence found that targeted therapies can reduce the risk of cancer recurrence. However, it is still in the discussion phase, and opting for targeted therapies for cancer treatment is an individualized decision the multidisciplinary clinical care team must make along with the patient.

Ask Your Doctor About Available Treatment Options

Your doctor may automatically perform comprehensive biomarker testing if you have been diagnosed with metastatic non-small, cell lung cancer. You should still talk with them about it to ensure smart treatment plans are made accordingly, especially prior to starting treatment.

Emerging data has shown that not all patients with actionable, active mutations respond well to certain targeted therapies. With that being said, it is critical that biomarker testing is performed to understand which available treatment options may be right for you.

“Data’s building to show that many patients who have these actionable mutations and should be going on these targeted pills don’t respond as well to immunotherapy,” says Rohs.

He expands on the topic by saying, “So, we may be finding the right treatments as well as avoiding the wrong ones by checking the genetics. What’s more,” he adds, “if you start on immunotherapy and then switch to a targeted drug after your doctor finds a related gene mutation, you may have more side effects. So, if your doctor is talking about immunotherapy, that’s drugs like pembrolizumab (Keytruda®), nivolumab (Opdivo®), and atezolizumab (TECENTRIQ®), make sure you have had biomarker testing first.”

When Should You Get it?

Let’s narrow down the discussion by listing when you should ask your clinical care team if comprehensive bookmarking testing is right for you. A comprehensive biomarker testing is appropriate when:

• Diagnosed with lung cancer
• Lung cancer comes back

As mentioned, all lung cancer patients should discuss biomarker testing with their clinical care team during diagnosis and treatment discussions. It is the best way to stay informed about your individualized cancer type and see if targeted therapy or immunotherapy is the right treatment option for you.

Which Biomarkers Should You be Tested for?

Patients with stage 4 (IV) or advanced stage adenocarcinoma should generally be tested for all of the following mutations listed:

• ALK
• EGFR
• BRAF
• MET
• KRAS
• RET
• NTRK
• PD-L1
• ROS1

Patients who have stage 1B-III cancer should be tested for gene mutation in EGFR once the tumor is removed. Patients should also consider mutations other than the ones mentioned above when discussing comprehensive biomarker testing with their healthcare team.

How is Biomarker Testing Performed?

Currently, medical professionals perform tissue biopsies to test or confirm a diagnosis of cancer. Practitioners use the same standard testing to find driver mutations in cancer cells. Your doctor can also perform liquid biopsies in some cases as well when traditional biopsies are unsafe to perform.

Tissue Biopsy

Tumor tissues can be obtained by using a variety of biopsy techniques. A healthcare team usually determines the technique after analyzing the size, shape, and location of the tumor. The team also takes the overall health of the patient into account when determining the specific technique being used. It is important that the procedure, risks, and benefits of the biopsy techniques are discussed.

Some of the tissue collection techniques include the following listed below:

• Endobronchial ultrasound-guided transbronchial (EBUS-TBNA)
• Bronchoscopy
• Thoracoscopy
• Transthoracic needle biopsy
• Mediastinoscopy
• Thoracentesis
• Mediastinotomy

Regardless of the biopsy technique the clinical care team utilized, it is important to confirm or find out about it before the procedure. The team will then remove the adequate tissue to perform the necessary biomarker analysis for mutations and other genetic markers. The tissue collected from the tumor may remain at the lab for further testing (if needed). Note that comprehensive biomarker testing is performed on both metastatic and primary tumors, depending on the patient’s treatment needs.

If the tumor tissue sample is not of the appropriate size to conduct multiple tests, the clinical care team gives priority to testing mutations that are suspected to be present in the cancerous cells. A trained pathologist will analyze the results and record them in a biomarker test report. It is always best to maintain a copy of all test and lab results (including those from biomarker testing) for your personal health files. Be advised that it may take up 2 to 4 weeks to receive your test results.

Liquid Biopsy

Although tissue biopsy is the standard testing method to confirm a cancer diagnosis and perform biomarker analysis, practitioners may also perform a liquid biopsy to find the most suitable and effective targeted therapies for the patients when traditional biopsies are unsafe or not feasible… Liquid biopsies, unlike traditional biopsies, do not use tumor tissue but obtain biomarkers in circulating fluids, such as the blood. Dead cancer cells release DNA, and it enters the plasma (this condition is scientifically called ctDNA or circulating tumor DNA). The two most well-developed biomarkers detected by liquid biopsy are circulating tumor cells (CTCs) and circulating cell-free tumor DNA (ctDNA).

The blood sample is tested in the lab for the presence of single or multiple mutations. Typically, the test process of the liquid biopsy takes less time compared to tissue biopsies. Both liquid biopsy and tissue biopsy run the same comprehensive biomarker testing to detect driver mutations. Although not standard practice, many studies have shown that liquid biopsies can be effective in detecting genetic mutations when traditional biopsies are not safe or feasible.

Final Thoughts

All in all, comprehensive biomarker testing is an important detection method healthcare teams use to diagnose lung cancer or a type of abnormal mutation in a cancerous tumor. It is an imperative lab test to rely upon when determining which treatment option is right for you. As we all know, treating any type of cancer is not a ‘one size fits all’ scenario. The mutation your specific cancer type possesses may be different from that of many other patients. Understanding biomarker testing and its role in diagnosis, as well as treatment, will ensure you get the best therapy options that fit your individual needs.

 

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