Understand The Liquid Biopsy For Cancer
- Liquid biopsy is a blood test that analyzes your blood for tumor cells that are present in the bloodstream, called circulating tumor cells (CTCs), as well as pieces of tumor cells, or circulating tumor DNA (ctDNA).
- Evidence of CTCs and ctDNA can provide genetic information from which a molecular profile can be created to provide a real-time snapshot of your cancer and to better personalize treatment and response to therapies.
- Liquid biopsy is a newly emerging field in cancer care, often used when people have metastatic or widespread disease and a repeat biopsy is needed to determine the future directions of therapy.
- A sample of a tumor biopsy is the preferred method for molecular testing. Liquid biopsy can be done in conjunction with the tumor-based testing for faster results or if a tumor biopsy is not possible.
- Although most often used in metastatic disease settings, current research is focused on the use for early cancer detection.
Why Would Liquid Biopsy Be Used?
Tissue biopsy is the traditional method of obtaining a cancer diagnosis and remains the gold standard. It is crucial in initial diagnosis and cancer workup and is often repeated when current therapy is not effective and new treatments are being considered. However, tissue biopsy and its repeated use in tailoring cancer treatment can have several limitations.
Tissue Biopsy Limitations:
- It is an invasive procedure, which depending on location and cancer type can be painful and potentially harmful to the patient.
- A tissue biopsy can be unsuccessful if the amount of cancer tissue collected is too small or the quality of the biopsy itself is poor.
- It can provide a limited picture of the cancer. Cancers are continuously mutating and evolving in different ways and in various locations, and a biopsy at a single site or in a limited area can miss these features.
Benefits of Liquid Biopsy:
- Liquid biopsy is non-invasive, only requiring a blood sample which is more convenient and easier to repeat.
- Liquid Biopsy can be used to detect cancer cells and their DNA mutations when there is not enough tumor or mass that can be targeted for a tissue biopsy.
- Liquid Biopsy can provide big-picture information regarding your cancer, as it collects pieces from cancer cells at multiple locations that come into contact with blood as opposed to one site from a tissue biopsy.
How Does Liquid Biopsy Work?“Molecular profiling of blood also known as liquid biopsies leverages the fact that tumors routinely shed free DNA in the bloodstream. That happens when the cancer cells die and release their contents,” says Dr. Anagnostou.
Cancer cells require a blood supply to grow and gather nutrients. Cancer cells can travel in the bloodstream in an attempt to spread and can also die for a variety of reasons including cancer therapies, a person’s immune system attacking them, or even the cancer cells themselves mutating and changing to the point where they cannot sustain life.
When cancer cells die, pieces of them are released into the bloodstream, namely ctDNA. According to Dr. Anagnostou, “These very small pieces of DNA can be ‘biopsied’ using a liquid biopsy compared to traditional tissue biopsy.” DNA is the genetic code that the cell uses as a blueprint to function. Cancer DNA is unique from the DNA of our normal cells because of specific mutations or changes in its code.
Many cancers such as colon, lung, breast, and prostate cancer all have unique mutations or alterations that can occur in the DNA, which provide valuable information including targetable mutations. Once identified, these mutations can be treated with specific medications that target these changes in the cancer DNA.
Am I a Good Candidate for Liquid Biopsy?
Typically, when diagnosed with cancer, an initial tissue biopsy and molecular testing results are used to inform treatment options and evaluate if you are a candidate for more targeted cancer therapies. Following the initial diagnosis of cancer, through treatment, and in the time following treatment, various DNA mutations can arise which can be tested. And according to Dr. Anagnostou, “That provides new information in a dynamic manner that allows for identification of new mutations that may be emerging during therapy, matching your tumor and you as an individual and a patient with the appropriate and more effective targeted therapy”.
Currently, liquid biopsy is most often performed when you have metastatic cancer and current therapies are not working. Metastatic cancer is when the disease has spread from the original site to other parts of the body. The decision for repeat biopsy and whether you need a tissue biopsy or liquid biopsy is a decision that you should discuss with your healthcare team.
Although liquid biopsy is most often used in combination with tissue biopsy to inform ongoing cancer therapies for a known diagnosis of cancer, new advances are making it possible to “capture minimal residual disease for individuals with early-stage cancer, or even be used for early cancer detection and an interception,” explained Dr. Anagnostou.
Essentially, the way cancer is typically diagnosed is when patients have symptoms, or a large enough volume of disease is seen on imaging or during evaluation by a healthcare provider. Because liquid biopsy is testing small pieces of cancer (ctDNA) or circulating tumor cells (CTCs) in the blood there is the possibility to detect cancer at its earliest stages or at first signs of recurrence which can potentially improve outcomes. Early detection and diagnosis of cancer with liquid biopsy is an ongoing field of investigation and more data is needed to better understand how to use a liquid biopsy in this manner.
Limitations of Liquid Biopsy and False Negatives
Currently, liquid biopsy is not a standard method for early diagnosis or detection of cancer. Liquid biopsy looks for very small pieces of tumor DNA and circulating cells in the blood which can be difficult to detect, as opposed to tissue biopsy which often takes a piece of a known tumor or mass. Because liquid biopsies are testing for the evidence or traces of a tumor with these small pieces of DNA and circulating cells in the blood and not testing a tumor itself, there is a higher chance the liquid biopsy misses the diagnosis and has a false negative result.
A false negative result occurs when any test incorrectly determines a negative result, meaning the test is actually positive. In this situation, that would mean that although there is cancer, the liquid biopsy did not detect evidence of circulating tumor DNA (ctDNA) or tumor cells in the blood (CTCs). Because of this, liquid biopsy is often used as a supplement to tissue biopsy and is typically considered only once there is not enough tumor available for testing or when unable to undergo further tissue biopsies.
What Liquid Biopsy is Available and What Can I Expect?
Several types of liquid biopsies have been approved by the U.S. Food and Drug Administration (FDA) including:
- The Cell Search Circulating Tumor Cell (CTC) Test is used for metastatic breast, prostate, and colon cancer to help monitor disease and provide a prognosis based on the levels of CTCs.
- Labcorp Plasma Focus is used for non-small cell lung cancer (NSCLC), colorectal, breast, esophageal, gastric, gastroesophageal junction carcinomas and melanoma through ctDNA. Results can come back in 7-10 days.
- Cobas EGFR Mutation Test v2 is used in non-small cell lung cancer (NSCLC) and detects a mutation in the EGFR gene through ctDNA which can help determine targeted treatment.
- Guardant 360 CDx is used in non-small cell lung cancer (NSCLC) and can help detect specific mutations in ctDNA to help guide treatment.
- FoundationOne Liquid CDx uses ctDNA to detect mutations in prostate, NSCLC, ovarian, and breast cancer to better tailor therapy.
When undergoing a liquid biopsy, a healthcare provider will take a sample of your blood, much like a complete blood count, which will be sent to an additional laboratory for testing. This is much less invasive and time-intensive than other biopsy procedures.