What Is A Biomarker?

Defining Biomarkers

The word biomarker is short for biological marker. A biomarker is any entity (thing) in the body that can take a snapshot or measure what is happening in the body at a given moment. Biomarkers can serve as early warning systems for your health.

For example, high cholesterol levels are a common biomarker for heart disease risk, and high levels of lead in the bloodstream show a possible need to test for nervous system and cognitive disorders, especially in children.

Biomarkers play an important role in helping us understand relationships between environmental exposures, human biology, and disease. Biomarkers can help us diagnose disease, choose therapy, and follow patients for treatment response, disease recurrence, and outcome. Scientists can use biomarkers to turn research findings into something useful in medicine and public health.

Biomarker Testing

Doctors often look at how changes in genes or proteins in a person’s cancer might affect their treatment options. We call this biomarker testing, where genes or proteins are the biomarkers.

Of note: Genes are pieces of DNA inside a cell. Each gene contains a code (instructions) needed to make a certain protein. Each protein has a given job to do in that cell.

(The word genes sounds like “jeans” when we say it. The word “proteins” sounds like “prohteens” when we say it.)

In biomarker testing, a sample of a patient tumor (cancer) is usually taken. Sometimes testing is done in blood. The use of biomarkers in the blood is being studied by many scientists and is growing quite quickly; however, currently, its use for treatment choice is limited. Biomarker testing in the blood is sometimes used to follow response to therapy and/or detect recurrence.

Biomarkers in tumor tissue can guide treatment choice and sometimes predict how well a patient might respond to treatment.

Value Of Testing

Although biomarker testing can help find the best cancer treatment for the person being tested, this testing cannot help everyone. There are various reasons for this, including:

A person may not be able to have a biopsy taken safely.
If a biopsy sample is taken, there may not be enough tumor tissue in the sample to do biomarker testing.
If biomarker testing is possible, the biomarkers in your cancer may not match any available therapies.
If a matching therapy is found, it may be off-label (it is FDA-approved to treat a different disease) and not covered by a person’s health insurance.
If a matching therapy is found, it may still be in clinical trials, and the person may not be able to participate.

Even if the test identifies a biomarker that matches an available treatment, there is no guarantee that the therapy will be effective for the person tested. Additional factors, such as how the cancer behaves and how a person’s body responds to the treatment, can influence how successful any treatment is.

Furthermore, not all cancer cells possess the same biomarkers, meaning that while a biomarker test may identify a treatment capable of killing some cancer cells, it might not affect all of them. This could lead to the growth of untreated cancer cells, making the treatment ineffective or causing the cancer to return quickly.

Biomarker testing of tumor tissue provides a single “snapshot” of the biomarkers present at the time of biopsy. The biomarkers can then change. So, what we see today may be different from what we see further down the line. If a cancer reappears after treatment, a healthcare provider may recommend doing another biomarker test to see the latest picture and change therapy as needed.

Why And Who Should Test

If a patient’s cancer contains one of the established biomarkers, treatments targeted to these biomarkers can be prescribed (personalized or “made-to-order” therapy). Patient response to these targeted treatments may be better than with general chemotherapy that is not “made-to-order.”

Biomarker tests can be quite helpful to people after they have been diagnosed with stomach cancer. If anyone with stomach cancer, particularly newly diagnosed, is unsure about any part of biomarker testing, they should discuss it with their doctor.

What To Expect When Testing

Biomarker testing for treatment choice might not be so available in some places.

Even when biomarker testing is available to look for gene or protein changes that might help treatment choice, a person might not have their tumor tested for these changes for a number of reasons.

It is important for the person with stomach cancer (the patient) and their loved ones to ask questions and know all their options. They should ask their healthcare team the following questions about the patient:

Should I have cancer biomarker testing done?
What information will the tests help you find out?
Will the tests help us choose which treatments are best for me?
How much will the tests cost? Will my insurance cover them?
If testing shows a specific treatment might be best for me, how much will this treatment cost? Will my insurance cover it?

In Tumor Tissue

Ways of measuring HER2

HER2 protein amounts are measured using IHC.

HER2 gene amounts “amplification” are measured using NGS or ISH.

Ways of measuring PD-L1

PD-L1 protein levels are tested using IHC.

Ways of measuring MSI-H/dMMR

MSI is tested by PCR or NGS.

MMR mutations are tested by IHC.

Ways of measuring TMB

High tumor mutational burden (TMB) is tested by NGS.

Explanation Of Technical Terms

IHC = immunohistochemistry

IHC is a laboratory method that uses antibodies to check for certain antigens (biomarkers such as HER2) in a tumor sample.

In our bodies, an antibody is an immune system protein that responds and binds to another protein called an antigen, causing an immune response. Each antibody can bind to only one specific antigen.

IHC involves using a similar antibody-antigen process. In IHC, an antibody locates antigens (e.g., HER2) in cancer biopsy tissue through the use of a visual marker. Fluorescent dye is the most common visual marker used, although there are others.

NGS = next-generation sequencing

NGS is used in high-tech laboratories to detect specific DNA (and RNA) sequences in cells. In the case of cancer biomarkers, NGS detects a specific mutated DNA sequence and the number of copies of this mutated DNA. This technology can be done on a large scale.

*It is important that all tests are done in a CLIA-certified lab.

ISH = in situ hybridization

ISH is used in the laboratory to detect specific DNA (and RNA) sequences in cells. In the case of cancer biomarkers, in situ hybridization detects a specific mutated DNA sequence and the number of copies of this mutated DNA.

PCR = polymerase chain reaction

PCR is a laboratory method that makes millions of copies of a DNA sample so that scientists can take a very small sample and make it big enough to see in detail.

*CLIA = Clinical Laboratory Improvement Amendments.

Only CLIA-certified labs meet federal regulations for clinical diagnostic testing, ensuring the quality of results.

Liquid Biopsy

Liquid biopsy—circulating tumor DNA (ctDNA) in a blood sample.

Liquid biopsy is now being used in patients with advanced gastric/GEJ cancer. The testing of biomarkers in blood can be done using NGS.

Biomarker testing in the blood can be complementary to tumor tissue-based testing, as both approaches can have limitations that the other can compensate for.

Results: What Testing Shows

Testing of all patients for HER2, PD-L1, and MSI biomarkers should be done when a patient is first diagnosed and if metastatic disease is confirmed or suspected. PD-L1 testing should be done in patients with locally advanced, recurrent, or mGC (see locally advanced, recurrent, or metastatic cancer treatments below for further information).

For patients with stages 0, 1, 2, or some stage 3 gastric/GEJ cancers:

Removal of the tumor using surgery is typically the first treatment choice.

Depending on the cancer stage and behavior, systemic therapies, including chemotherapy, (possibly) targeted therapy, and radiation therapy, are combined with surgery.
- One or a combination of systemic therapies are surely used for stage 2 or 3 cancer.
- Systemic therapy might also be used for stage 1 cancer.
- There are open clinical trials of immunotherapy and biomarker-targeted treatment if a patient is “a fit” for any of these trials (you will hear doctors talk about being “eligible” or “meeting the criteria”) and if the treating physician thinks the trial is a good idea for that particular patient.

Stage 0 cancer is abnormal cells that look like cancer cells under a microscope. These cells are found only in the stomach and haven’t spread to nearby tissue.

Stage 1 cancer is generally small, contained within the stomach, and has not spread to the lymph nodes or other parts of the body).

Stage 2 or 3 cancer has some degree of spread into other tissues but can be surgically removable.

For patients with stage 4 (metastatic) and some stage 3 (locally advanced unresectable or recurrent) gastric/GEJ cancers:

Treatments other than surgery are needed. This treatment is discussed in the next section (locally advanced, recurrent, or metastatic cancer treatments)

Metastatic means that the cancer has spread to other parts of the body

Locally advanced unresectable means that the cancer has spread within the stomach/GEJ in a way that cannot be removed by surgery

Recurrent means the cancer keeps coming back

Risks Of Testing

Biomarker testing can provide different types of results. Here are some possibilities:

The test may reveal that a person’s cancer has a biomarker that can be targeted by a known treatment. This could be an option to help fight that cancer. The treatment might be approved by the FDA, or it may be an off-label treatment (it is FDA-approved to treat a different disease) or part of a clinical trial.
The results may indicate that a person’s cancer does not have certain biomarkers, meaning some treatments are unlikely to work. This information can help avoid treatments that will not be effective for that person’s specific type of cancer.
The test might suggest how a person is likely to benefit from treatment in general without pinpointing a particular treatment. For instance, it might indicate that a person’s cancer is more likely to return after the initial treatment. In such cases, receiving additional treatment could help reduce this risk.
Certain changes may be discovered in a person’s cancer cells that are not useful for making treatment decisions. These changes might include a gene alteration that is considered harmless (benign) or whose effects are not clearly understood (known as a variant of unknown significance, or VUS). Although these results might appear on the lab test report, they are not used to determine the appropriate treatment plan.

Please note that specific biomarker results and their implications should always be discussed with a healthcare provider to make informed treatment decisions.

Cost Of Testing

The cost of biomarker testing and the treatment choices made as a result of this testing can sometimes be a concern:

Tests for gene and protein changes can be expensive, especially if many changes are being assessed, and insurance might not cover all testing costs.
For people whose best treatment option is a specific targeted therapy or immunotherapy based on their cancer’s gene or protein changes, the treatment itself might be expensive.

More information* on insurance coverage:

For people with advanced cancer, some biomarker tests are covered by Medicare and Medicaid.
Private insurance companies often cover the cost of biomarker testing if there is enough proof that the test is needed to guide treatment decisions. See the download of approved biomarkers.
Tests without enough proof to support their value may be viewed as experimental. In these cases, insurance might not cover the tests or the biomarker-suggested treatment. This type of biomarker testing might be done as part of a clinical trial of a new cancer treatment.
- If a person joins one of these clinical trials, the cost of biomarker testing for any new biomarkers and the recommended treatments should be covered by the study.

*A person’s healthcare team can provide more specific information about related costs and what a person’s insurance will cover. They can also provide clinical trial information.