6 Reasons Biomarker Testing Is Important for Endometrial Cancer

Medically reviewed by Howard Goodman, M.D.
Written by Maureen McNulty
Posted on September 6, 2023

In endometrial cancer (uterine cancer), tumor cells may contain genes, proteins, or other molecules that aren’t found within healthy uterine cells. These different molecules, caused by genetic abnormalities, are called biomarkers or molecular markers. Through biomarker testing, a doctor can determine which biomarkers you have.

Knowing which biomarkers your tumor contains can be helpful in several ways. Biomarkers can provide clues about how your cells will grow and tell your doctor which endometrial cancer treatments are most likely to be effective.

Read on to learn more about how your doctor can use your cancer biomarkers to offer you personalized medicine.

How Does Biomarker Testing Work?

Your doctor “reads” the biomarkers on your cancer cells using biomarker testing, also called tumor subtyping, genomic profiling, or molecular testing.

Biomarker testing is often performed after a biopsy (removal of a small piece of tissue) or surgery to take out a tumor. Your doctor sends this tissue to a lab, where it undergoes testing to show whether biomarkers are present. Laboratories use a variety of tests, such as gene sequencing or immunohistochemistry, to look for genetic mutations or the presence of an abnormal protein.

Biomarkers may also be present in the blood. Some cancer cells release substances that can be detected with a simple blood test.

How Are Your Biomarker Testing Results Used?

Following are some ways that knowing your tumor’s biomarker status may help as you undergo treatment for endometrial cancer.

1. Finding Effective Treatments

Biomarkers help predict which treatments can target your cancer cells. For example, a certain drug may be able to recognize a specific change resulting from a biomarker found only in cancer cells and kill them while sparing healthy cells.

Doctors use various classification systems to look for biomarkers and assign your cancer a risk subgroup. You may need more aggressive therapy if you have high-risk cancer. These systems — which include The Cancer Genome Atlas (TCGA) Molecular Classification of Endometrial Cancer and the Proactive Molecular Risk Classifier for Endometrial Cancer (Promise) — assign risk based on biomarkers including:

  • Mismatch repair deficiency (also called deficient mismatch repair, or dMMR) — This biomarker indicates that your cancer cells have abnormalities in certain proteins that are supposed to fix gene mutations, which may cause mutations to build up in your tumor.
  • POLE mutations — You have multiple mutations in a gene called POLE, which can also result in the accumulation of many mutations in your tumor cells.
  • Copy number high — There are many amplifications (copies) or deletions of genes throughout your cancer cells.
  • Copy number low — There are very few gene amplifications and deletions within your tumor.

Biomarker testing may particularly be helpful for people with tumors that are resistant to standard chemotherapy treatments. This may occur if you have advanced-stage endometrial cancer or if your cancer recurs (returns after being treated). Biomarker testing can pinpoint immunotherapies or targeted therapies that may work better than toxic chemotherapy medications.

For example, the U.S. Food and Drug Administration (FDA) has approved the immunotherapy drugs dostarlimab (Jemperli) and pembrolizumab (Keytruda) as treatments for advanced or recurrent endometrial cancer with dMMR. Pembrolizumab is indicated to be used in combination with the targeted therapy drug lenvatinib (Lenvima). The combination of pembrolizumab and lenvatinib is also approved to treat non-dMMR advanced endometrial cancer.

2. Assessing How Well Treatments Are Working

Your doctor may recommend that you undergo biomarker testing at several points in your treatment journey to determine whether treatments are successfully killing your cancer cells. For example, if your cancer cells contain a certain biomarker, levels of this biomarker should drop if your treatment plan is destroying your tumor.

3. Helping You Avoid Side Effects

When you know the treatments that are most likely to work, you also know the treatments that are most likely to fail — and you can stay away from them. Additionally, certain biomarkers may render a treatment ineffective, so this type of testing helps you understand which therapies not to use.

This is important because most cancer treatments come with side effects. Research has shown that when you have a lot of side effects or take multiple medications, you are less likely to follow through with your treatment plan. This can make your cancer more difficult to treat and lead to worse outcomes. Using only the treatments that are likely to be effective can help set you up for treatment success.

Experiencing treatment-related side effects can also harm your sense of well-being and lead to a worse quality of life. Using biomarker testing to rule out certain treatments may make your treatment journey easier.

Read more about how to get support as you treat endometrial cancer.

4. Informing Your Prognosis

Most people diagnosed with endometrial cancer have a good prognosis (outlook). However, certain biomarkers serve as prognostic factors — they help indicate when you have more severe disease. For example, changes in the tumor protein 53 (TP53) gene may indicate that you have a poor prognosis, while POLE gene mutations are linked to a lower chance of having your cancer recur.

One study found that multiple biomarkers in the blood were linked to endometrial cancer survival rates. Researchers found that people with this condition were likely to have a worse prognosis when they had high levels of:

  • Cancer antigen 125 (CA-125)
  • Cancer antigen 15-3 (CA 15-3)
  • C-reactive protein
  • D-dimer

Understanding your prognosis aids you when choosing a cancer treatment plan. For example, you may want to use more aggressive treatments if biomarker testing shows that your cancer may grow and spread more quickly. Additionally, knowing your prognosis helps you better understand what to expect and make a plan for your future.

5. Qualifying You for Clinical Trials

Researchers use clinical trials to test whether potential new treatment plans are safe and effective. If you enroll in a clinical trial, you may receive new therapies in which the full scope of benefits and side effects may not yet be fully understood. However, these treatments may be more effective than ones you would be able to receive from your doctor.

Many clinical trials enroll people with a certain type of cancer, such as advanced endometrial cancer. However, some trials also look for people with a certain type of biomarker. This may be the case for clinical trials that target a specific type of protein or gene change.

For example, one current clinical trial is recruiting people with endometrial cancer who have cells that are folate receptor-alpha (FR-alpha)-positive in addition to microsatellite stable. This trial is studying a medication, previously approved to treat breast cancer, that might help block FR-alpha.

Many other endometrial cancer trials studying other biomarkers are also underway. Take a look at ClinicalTrials.gov or the National Cancer Institute’s database of trials to learn more about current studies.

6. Showing Genetic Changes That May Affect Your Family

Biomarker testing is generally different from genetic testing. Biomarker testing shows you changes or mutations that developed within your cancer cells that aren't present in your healthy cells and don’t run in families.

Genetic testing, on the other hand, looks for gene changes found in all of the cells in your body. This type of mutation — called a germline or inherited mutation — can be passed down from parent to child. When you have a germline mutation, you have an elevated risk of developing cancer. If family members also have the mutation, their risk may be increased, too.

Biomarker tests sometimes show changes that are actually inherited mutations. The results of biomarker testing indicate that you may need additional genetic testing, which can help your family understand their own cancer risk levels. Ask your doctor to help you understand whether genetic testing may be a good idea.

Talk With Others Who Understand

On MyEndometrialCancerCenter, the site for people with endometrial cancer and their loved ones, people come together to gain a new understanding of endometrial cancer and share their stories with others who understand life with the condition.

Are you living with endometrial cancer? Did you undergo biomarker testing of your cancer cells? Share your experiences in the comments below.

References
  1. Biomarker Testing for Cancer Treatment — National Cancer Institute
  2. Current and Emerging Prognostic Biomarkers in Endometrial Cancer — Frontiers in Oncology
  3. Biomarker Tests and Cancer Treatment — FORCE
  4. Biomarkers, Targeted and Immunotherapies — FORCE
  5. Gynecological Cancers Caused by Deficient Mismatch Repair and Microsatellite Instability — Cancers
  6. POLE Mutations Improve the Prognosis of Endometrial Cancer via Regulating Cellular Metabolism Through AMF/AMFR Signal Transduction — BMC Medical Genetics
  7. The Role of Biomarkers in Endometrial Cancer and Hyperplasia: A Literature Review — Acta Oncologica
  8. FDA Approves Immunotherapy for Endometrial Cancer With Specific Biomarker — U.S. Food and Drug Administration
  9. FDA Converts to Full Approval Indication for Keytruda (Pembrolizumab) for Certain Adult and Pediatric Patients With Advanced Microsatellite Instability-High (MSI-H) or Mismatch Repair Deficient (dMMR) Solid Tumors — Merck
  10. Tests for Endometrial Cancer — American Cancer Society
  11. Chemotherapy and Radiation Side Effects — Cleveland Clinic
  12. Treatment of Older Women With Endometrial Cancer: Improving Outcomes With Personalized Care — American Society of Clinical Oncology Educational Book
  13. Health-Related Quality of Life Before and During Chemotherapy in Patients With Early-Stage Breast Cancer — Ecancermedicalscience
  14. Current and Emerging Prognostic Biomarkers in Endometrial Cancer — Frontiers in Oncology
  15. Multivariate Analysis of Prognostic Biomarkers in Surgically Treated Endometrial Cancer — PLOS One
  16. Understanding Cancer Prognosis — National Cancer Institute
  17. What Are Clinical Trials and Studies? — National Institute on Aging
  18. A Phase 2 Study of Mirvetuximab Soravtansine (IMGN853) and Pembrolizumab in Endometrial Cancer (EC) — ClinicalTrials.gov
  19. Find NCI-Supported Clinical Trials — National Cancer Institute
    Howard Goodman, M.D. is certified by the American Board of Obstetrics and Gynecology and specializes in the surgical management of women with gynecologic cancer. Review provided by VeriMed Healthcare Network.. Learn more about him here.
    Maureen McNulty studied molecular genetics and English at Ohio State University. Learn more about her here.
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