Liquid Biopsy: Definition

A liquid biopsy is a medical test that detects signs of disease, such as cancer, in a sample of body fluid—most often blood. Unlike a traditional biopsy, which involves removing a small tissue sample with a needle or during surgery, a liquid biopsy is minimally invasive and can be done with a simple blood draw. Liquid biopsies are most commonly used to find fragments of tumor DNA or other cancer-related materials circulating in the bloodstream.

Why is a liquid biopsy done?

Doctors order liquid biopsies for several reasons:

• To detect genetic changes in cancer without the need for a surgical procedure.
• To help choose targeted therapies that match the genetic profile of a patient’s tumor.
• To monitor how well cancer treatment is working over time.
• To check for cancer recurrence after treatment.
• To provide information when a tissue biopsy is not possible due to the location of the tumor or the patient’s health condition.

Because it can be repeated more easily than a surgical biopsy, a liquid biopsy is also helpful for tracking changes in a cancer’s genetic profile over the course of treatment.

How is a liquid biopsy performed?

For most liquid biopsies, a healthcare professional takes a blood sample from a vein in your arm, similar to other routine blood tests. The blood is then sent to a specialized laboratory where it is processed to separate plasma (the liquid part of blood) from the blood cells. Laboratory scientists use highly sensitive techniques to detect and analyze very small fragments of DNA, RNA, or other molecules released from tumor cells into the blood.

In some cases, other fluids—such as urine, cerebrospinal fluid (CSF), or pleural fluid—may be used instead of or in addition to blood.

What does a liquid biopsy look for?

Liquid biopsies often look for circulating tumor DNA (ctDNA)—small fragments of genetic material released into the blood when cancer cells die and break apart.

A liquid biopsy may also look for:

• Circulating tumor cells (CTCs): Whole cancer cells that have entered the bloodstream.
• RNA changes: Abnormal patterns of gene activity related to cancer.
• Proteins or other biomarkers linked to specific cancers.

The exact targets depend on the type of test and the disease being investigated.

Common genetic changes assessed in a liquid biopsy

Many liquid biopsies focus on detecting genetic mutations that can help guide treatment. Common examples include:

• EGFR mutations in lung cancer.
• KRAS and NRAS mutations in colorectal cancer.
• BRAF mutations in melanoma and other cancers.
• ALK, ROS1, and RET gene rearrangements in certain lung cancers.
• PIK3CA mutations in breast and other cancers.

These results can help determine whether a patient is eligible for a targeted therapy that specifically works against cancer cells with those mutations.

Types of cancer currently tested for with a liquid biopsy

Liquid biopsy is used most often in cancers where identifying genetic changes can directly guide treatment decisions or where tissue biopsy is difficult to perform.

Common examples include:

• Non-small cell lung cancer (NSCLC): Liquid biopsy can detect mutations such as EGFR, ALK, ROS1, and MET, which may determine eligibility for targeted therapy.
• Colorectal cancer: Testing can identify mutations like KRAS, NRAS, and BRAF that help predict response to certain treatments.
• Breast cancer: Liquid biopsy may detect PIK3CA mutations or monitor HER2 status to guide therapy choices.
• Melanoma: Tests can identify mutations such as BRAF, NRAS, and KIT, which influence treatment planning.
• Prostate cancer: Liquid biopsy can detect DNA repair gene mutations (such as BRCA1 and BRCA2) that may make patients eligible for certain targeted drugs.
• Other cancers: In some cases, liquid biopsy is used in pancreatic, ovarian, bladder, or head and neck cancers for genetic profiling or monitoring.

While these are the most common cancers currently tested, research is rapidly expanding the role of liquid biopsy to more cancer types and clinical situations.

How may liquid biopsy results be reported?

In your pathology or laboratory report, the results may be presented as:

• Detected mutation: A specific genetic change was found, often listed by the affected gene name (e.g., EGFR exon 19 deletion).
• No mutation detected: No targeted genetic changes were found in the sample.
• Variant of uncertain significance (VUS): A genetic change was found, but it is not yet known if it is related to cancer or if it affects treatment.
• Quantitative result: Some tests also provide information on the amount of ctDNA detected, which may change over time with treatment.

Your doctor will interpret these results in the context of your overall medical history, cancer type, and treatment plan.

What are the advantages of a liquid biopsy?

A liquid biopsy has several benefits compared to a traditional tissue biopsy:

• Less invasive: It usually only requires a blood draw, which is quicker, easier, and more comfortable.
• Safer: There is no surgical wound, so the risk of bleeding or infection is very low.
• Easier to repeat: Because it’s simple to do, liquid biopsies can be repeated over time to monitor treatment or check for cancer recurrence.
• Helpful when tissue biopsy isn’t possible: It can provide valuable information if the tumor is in a hard-to-reach location or if a patient isn’t able to have a surgical procedure.

What are the disadvantages of a liquid biopsy?

Liquid biopsies also have some limitations:

• May not detect all cancers or mutations: Some tumors release very little DNA into the blood, which can lead to a false-negative result.
• Cannot always replace a tissue biopsy: A tissue sample is still needed to confirm a cancer diagnosis and to see how the tumor looks under the microscope.
• Limited information: While it can show genetic changes, it doesn’t give details about the tumor’s structure or other important features.
• Availability and cost: Some liquid biopsy tests are not available everywhere and may not be covered by all insurance plans.

Questions to ask your doctor

• Why are you recommending a liquid biopsy for me?
• What specific genetic changes will this test look for?
• How will the results affect my treatment options?
• Will I still need a traditional tissue biopsy?
• Can this test be repeated to monitor my cancer over time?