Cancer Treatment: What Are Biomarker Tests?

What are biomarkers?

Cancers are made up of abnormal cells. These cells can produce different types of abnormal substances, called biomarkers (or tumor markers). Biomarkers may be found within or around tumors, in blood, urine and other body fluids. They include: 

• proteins.
• genetic material (gene mutations, abnormal chromosomes, DNA or RNA, fused genes).
• cellular material.

What are biomarker tests used for?

Biomarker tests may aid decision-making in different ways:

• Aiding in treatment selection: Some cancer treatments work best in people with certain biomarkers. In these cases, biomarker testing can help identify people who are most likely to respond to a particular treatment. 
• Measuring risk for recurrence: Some tests predict how fast a cancer is growing and the risk for recurrence. Examples include OncotypeDX, Mammaprint and Endopredict for breast cancer and OncotypeDX and Prolaris for prostate cancer. 
• Monitoring response to treatment, progression or recurrence: These tests often measure changes in biomarkers over time to learn if the cancer is responding to treatment. Examples include CA125 testing to monitor ovarian cancer and PSA testing to monitor prostate cancer.
• Detecting cancer: Some biomarker tests are being studied to see if they can be used for early detection of cancer.  

What type of sample is needed for biomarker testing?

The type sample used for a biomarker test depends on the test being run. 

• Most biomarker tests are run on a piece of tissue from the tumor obtained by biopsy or surgery. Some biomarker tests may be run on stored tumor tissue that was collected and saved at the time of your diagnosis, even if your biopsy was done a while ago. If you have enough tumor tissue stored, using this "archival tissue" may spare you from a new biopsy. 
• Some tests require fresh tissue, which means you may need a new biopsy. This is because some tumor biomarkers change over time as cancer cells grow, spread or become resistant to treatments. 
• Some tumors may release cells or biomarkers into the blood, urine or other fluids. This provides a more convenient way to find cancer or to monitor response to treatment without the need for a tissue biopsy. These biomarker obtained from fluids are called liquid biopsies. 

What are liquid biopsies?

Liquid biopsies are tests that look for signs of cancer in blood or other body fluids. Liquid biopsies can be categorized by the type of substances they detect: 

• Tests that look for cancer cells in the bloodstream are called Circulating Tumor Cell (CTC) tests. 
• Tests that look for DNA fragments from cancer cells are called circulating tumor DNA (ctDNA tests). 

Liquid biopsies can be categorized by how they are used: 

• Treatment selection tests look for biomarkers that guide selection of targeted treatments.
• Minimal residual disease (MRD) tests look for evidence of cancer remaining or recurring after treatment or surgery. 
• Single-site tests and multi-cancer detection tests (MCD) screen are used for screening and detection of cancer. 

Tumor testing vs. genetic testing for an inherited mutation

Tumor biomarker tests look for gene mutations in cancer cells and other changes caused by the presence of cancer. These tests differ from genetic tests for inherited cancer risk (also called "germline genetic testing.")  

As cells become cancerous, they develop many gene mutations that cause abnormal growth. These gene changes, which occur after you are born and throughout your life—are known as acquired or "somatic" mutations. Acquired mutations are different than inherited mutations, which are passed on from parent to child and are present at birth in every cell.

Information provided by tumor testing and genetic testing may overlap. If a person is born with a genetic mutation and later develops cancer, that mutation is likely to show up when the tumor is tested. This is because the cancer grew from the person’s own cells. So  someone born with a BRCA1 mutation has that mutation every one of their cells. If they develop ovarian cancer, the cancer cells will usually have the same BRCA1 mutation. Similarly, if a person is born with an inherited MSH6 mutation and develops colorectal cancer, the tumor will often show the same mutation and may also have features such as high microsatellite instability (MSI‑High).

Not all tumor biomarker tests can distinguish inherited mutations from acquired mutations. If your biomarker test shows a mutation, ask your doctor if it may be hereditary and if you should have genetic testing for an inherited mutation. 
 

Which biomarkers are used for treatment selection?

Some therapies work best in cancers that have specific biomarkers. Biomarker tests may be used to select the best targeted therapy to treat a particular cancer. More than 100 targeted therapies have FDA approval to treat different types of cancers. 

Some biomarkers may be found in many types of cancers, others may be specific to a certain type of cancer. Below you can find links to information on the biomarkers most commonly found in different types of cancer.  

DNA damage repair biomarkers

Certain genes are important for repairing DNA damage. These genes are sometimes referred to as "DNA damage repair" (DDR) genes. 

• In a normal cell, a mutation in a DDR gene increase the chance that it will become cancer. This is why an inherited mutation in a gene that repairs DNA damage increases the risk for cancer.
• In a cancer cell, a mutation in a DDR gene can keep it from repairing damage caused by treatment. This means that cancer cells with mutations in these genes may be more sensitive to certain treatments.

Two main types of DNA damage repair genes are linked to increased cancer risk and improved response to certain types of treatment: 

• "Homologous recombination response" (HRR) genes 
• "Mismatch repair" (MMR) genes

Genetic tests can identify people with an inherited mutation in a DDR gene. Biomarker tests can find tumor cells that have difficulty repairing these types of DNA damage. 

Homologous recombination repair biomarkers: HRR and HRD-positive

HRR (Homologous Recombination Response) genes repair a type of DNA damage known as "double-stranded DNA damage." Cancers with difficulty repairing this type of DNA damage are known as HRD (homologous recombination deficient). Cancers that have difficulty repairing this type of DNA damage may respond better to treatment with a type of targeted therapy known as PARP inhibitors. 

• Genetic testing for inherited (germline) mutations may help identify people who would benefit from treatment with a PARP inhibitor. This includes people with advanced breast, ovarian, pancreatic or prostate cancer. 
• Tumor testing for acquired (somatic) mutations may help identify people who would benefit from treatment with a PARP inhibitor. This includes people with advanced ovarian or prostate cancer. 
• HRD testing is a special type of biomarker test to find tumors that have difficulty repairing double-stranded DNA damage. HRD testing looks for "genomic instability" within tumors, that makes it hard for them to repair DNA damage. Tumors that have this type of genomic instability are sometimes called "HRD-positive." HRD testing can help find ovarian cancers that respond better to PARP inhibitors. HRD testing may also be used to find people who qualify for certain clinical trials. 
• HRR testing is a special type of biomarker test to find tumors that have certain mutations that may make them sensitive to PARP inhibitors. HRR testing can help find prostate cancers that respond better to PARP inhibitors. HRR testing may also be used to find people who qualify for certain clinical trials. HRR testing looks for tumor mutations in the following genes: 

Mismatch repair biomarkers: MSI-High and dMMR (MMR-d)

Mismatch repair (MMR) genes repair DNA damage that occurs during cell division. Tumors with mutations in mismatch repair genes are called "mismatch repair deficient" (also called dMMR or MMR-D). These tumors typically have an abnormality known as "microsatellite instability high," MSI-High or MSI-H for short. Mutations in the Lynch syndrome genes are often associated with dMMR and MSI-H tumors. 

Testing tumors for dMMR/MMR-D or MSI-High can be important, because these tumors are more likely to respond to a type of immunotherapy known as immune checkpoint inhibitors. 

Table of biomarkers

The table below highlights biomarkers that may help guide cancer treatment decisions and are most relevant to the cancers and inherited gene mutations featured on the FORCE website. This is not a complete list of all cancer biomarkers or treatments. Other biomarkers may be used to help select treatments or identify clinical trial options. Talk with your healthcare team about whether additional testing may help guide your treatment.

Minimal residual disease (MRD) testing

Minimal residual disease (sometimes called molecular residual disease or measurable residual disease) testing is a type of liquid biopsy that looks for the presence of cancer in the blood after treatment. MRD tests may be used in the following ways:

• To identify people who would benefit from adjuvant treatment (after surgery).
• To identify people whose cancer is likely to recur (return).
• To help guide when and if tumor screening should be considered after treatment.
• To monitor a cancer to see if it is responding to therapy.
• To detect a cancer recurrence.

The test can be used to determine how well a treatment worked and the likelihood of cancer coming back after treatment. Although the test is available, it is not yet included as standard-of-care in most cancer treatment guidelines. Research is ongoing to determine the best use of MRD tests as part of post-treatment care.

Questions for your doctor

Below are some questions to ask your doctor about biomarker testing: 

• Has my tumor been testing for biomarkers? If so, what were the results? 
• Is there a targeted therapy that might be more effective for my cancer? If so, will I need a tissue biopsy or is a liquid biopsy an option?
• How will you monitor my cancer for recurrence?
• Are there liquid biopsies that can tell if my cancer has recurred?