Diagnosed with Non-Small-Cell Lung Cancer? Here's Why You Need Biomarker Testing

In recent years, advancements in the way doctors classify non-small cell lung cancer (NSCLC) have led to huge strides in the treatment of the disease.

Until a little over a decade ago, all NSCLC types were essentially treated in the same way - typically with chemotherapy. Now, specific types of NSCLC can be managed based on the biomarkers that characterize them.

Biomarker testing, which is sometimes called genomic or molecular testing, looks for changes in a tumor's DNA, or genetic makeup, according to the American Lung Association (ALA) . When these biomarkers are identified, doctors can now match the type of NSCLC you have with the treatments that will provide the most benefit, potentially improving or extending your life.

The Role of Biomarkers in NSCLC

There are several biomarkers used to determine treatment in NSCLC. These include gene mutations - ALK, BRAF, EGFR, HER2, KRAS, MET, NTRK, RET, ROS1, and STK11 - in tumor cells that can be "targeted." Called targeted therapies, these drugs target cancer cells with alterations in specific genes, leaving healthy cells untouched, more or less, according to the Lung Cancer Foundation of America (LCFA) .

A second group of biomarkers in NSCLC comprises immunotherapy biomarkers, such as the PD-L1 protein, the LCFA notes. This protein is known to control the body's immune response. Its presence can tell your doctor if you will respond to immunotherapy, a more recently approved treatment that's designed to harness your own immune system to fight the NSCLC, according to the LCFA.

It's now recognized that many people with NSCLC have gene alterations that drive the growth of the cancer, according to research . In recent years, more and more of these drivers of gene mutations have been identified. And a better understanding of the biology of these genes has allowed for the development of new targeted therapies.

"I explain these biomarkers to patients as kind of like the Achilles' heel of a cancer," says Zosia Piotrowska, MD , an oncologist at Massachusetts General Hospital and assistant professor of medicine at Harvard Medical School in Boston. "When we can find them, we can treat them with targeted therapy in some cases."

Testing for Gene Alterations

Biomarkers in NSCLC are found through a technology called next-generation sequencing (NGS), says Dr. Piotrowska. This test looks for genetic alterations, such as mutations, fusions, or rearrangements.

All of these factors together help narrow down the type of disease that doctors are dealing with and the treatment they will choose to attack the cancer.

"Molecular testing is so important in NSCLC, because it helps us to really understand the specifics of a patient's lung cancer [and] sometimes the reasons that a lung cancer developed. And most important, it helps us select the best therapy for patients," Piotrowska says.

How Is Testing Conducted?

Biomarker testing in NSCLC is done either with a biopsy (a tissue sample from a tumor, collected during a minor surgical procedure) or a blood test called a liquid biopsy or plasma test, according to Piotrowska.

In a liquid (blood) biopsy, your oncologist will extract samples of your blood cells for analysis. The process, which is similar to how blood is collected for routine testing, is noninvasive, she says.

From collected samples, pathologists work to isolate the DNA from the cancer cells and perform NGS to look for specific mutations or alterations, Piotrowska says. For example, one study reports that isolated EGFR mutations in plasma samples can predict and help monitor treatment response.

Liquid biopsies are becoming more common in NSCLC and are used in place of traditional tissue biopsies in some cases, she adds. These biopsies look for circulating tumor DNA that has been shed by cancer cells into a person's bloodstream. Pathologists can then isolate those DNA fragments and conduct sequencing to look for specific changes in genes. A study published in the journal Nature Medicin e found that liquid biopsies detected aggressive genomic variations that tissue biopsies missed.

It can take up to four weeks to get the results from a biomarker test - an average of 33 days for a tissue biopsy and 11 days for a liquid biopsy, according to the Nature Medicine study, but taking this time helps your doctor complete your diagnosis.

Targeting Gene Alterations

Once testing is conducted and genetic alterations are identified, doctors can work to develop a treatment plan that is specifically designed to target those alterations, Piotrowska explains.

"The reason that molecular testing is so important is that patients who have an alteration in one gene are likely to benefit from one targeted therapy, whereas patients who don't have an alteration in that gene are not going to respond to that targeted therapy," she says. "Again, the goal of this type of testing is to identify everything we can about the cancer to try to select the best and most effective therapy for that patient."

The first mutation researchers determined could be treated with targeted therapy in NSCLC was in the epidermal growth factor receptor (EGFR) gene, according to the ALA. Once doctors realized that patients with this type of mutation could be effectively treated with EGFR-targeted therapies, research turned toward identifying other targetable mutations.

Approved targeted therapies now exist for an increasing number of biomarkers, including ALK, BRAF, EGFR, HER2, MET, NTRK, RET, ROS1, STK11, and, most recently, KRAS, according to the ALA. But it's important to note that not everyone with NSCLC will have an alteration that can be treated with a targeted therapy. In addition, another medical condition may make some people ineligible for these treatments, due to potential side effects.

Just as the presence of genetic alterations helps doctors narrow down which treatment will likely benefit a person most, the absence of those alterations also informs a person's treatment course, Piotrowska says. And since NSCLC research is constantly advancing, the more knowledge a doctor has about their patient's cancer, the more able they are to potentially match their patients to emerging treatments. These patients may have some other biomarkers for which a clinical trial is available, for example.

Having one particular genetic alteration isn't necessarily better or worse than having another, but some do have more therapeutic options, Piotrowska notes. Knowledge of the presence or absence of these alterations also tells doctors what not to do.

For example, certain treatments, such as immunotherapy, are going to be less effective for cancers with particular alterations, such as ALK and EGFR, she says. But upcoming research is looking at combining chemotherapy with immunotherapy for ALK and EGFR mutations.

"Some have been known about for longer, such as EGFR and ALK, and some are more recent discoveries and have only recently had approved targeted therapies. So varying numbers of treatment options exist for each of these oncogenes, but I hope that will change in the future," Piotrowska says. "I think, at the end of the day, the best thing for each individual patient is to do the appropriate testing."

When Should Testing Be Done?

The best time for molecular testing is right after the initial diagnosis. "The goal is to have this information as quickly as possible to help us select the best treatment for that patient," Piotrowska says.

For some people, molecular testing will have to be repeated later in the treatment course to modify therapy as needed, particularly if the tumor stops responding to the current regimen, according to the National Comprehensive Cancer Network . But new research is trying to stay ahead of the game by looking into ways to prevent tumor resistance.

What Comes After Testing?

Receiving the results of molecular testing can often take a few weeks, and you may be asked to wait for these results before treatment can be started.

Piotrowska acknowledges that this can be an incredibly difficult time for you and your family, particularly if you've just been told you have NSCLC. Understandably, you may be anxious to start treatment, she says.

Even so, she encourages people diagnosed with the disease to ask their doctors plenty of questions during this process. This is especially important because the results of these tests may or may not be routinely shared with you.

"It's important for patients to feel empowered," Piotrowska says. "Ask your providers about what type of testing was done, what was learned about your cancer, and finally, how that will impact treatment decisions going forward."

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