Liquid Biopsy - What They Are, How They Work

by Jane Ashley

Most of us know what a biopsy is — a biopsy is a procedure where a sample of tissue is removed to determine if a tumor or suspicious area contains cancer cells. The tissue sample is removed by a surgical procedure (either a small sample is obtained, or the entire lump is removed) or by a needle.

Liquid Biopsy

Most people haven’t heard about another kind of biopsy. It’s called a liquid biopsy.

What is a liquid biopsy?

Technically, a liquid biopsy is a body fluid sample (usually blood) to find significant biomarkers to personalize and more effectively treat and monitor someone’s cancer. Cancerous tumors shed ctDNA (actual tumor-derived deoxyribonucleic acids).

Although researchers have known that circulating cfDNA is present in our bloodstreams since 1948, it was not until 1977 that researchers detected higher levels of cell-free DNA (cfDNA) in the serum and plasma of cancer patients compared to people without cancer. Yet researchers were stymied as to how to use this information. Another obstacle was that existing technology until recently was not sensitive enough to measure these tiny particles.

The first commercial liquid biopsy became available in 2014. Fast forward to 2020, and we are seeing several emerging companies that provide liquid biopsies.

How are liquid biopsies used?

The biomarkers discovered through a liquid biopsy are like “fingerprints” of our particular cancer. Liquid biopsies can distinguish DNA shed directly from tumors. Liquid biopsies detect the presence of specific biomarkers for several cancers, including breast, colorectal, and lung cancer.

Liquid biopsies help oncologists in many ways.

• Guide and access the effectiveness of treatment. The presence of certain biomarkers, such as EGFR, KRAS mutation, or good expression of PD-L1, guide our oncologist as to which medical therapy will be most effective. Once treatment begins, a liquid biopsy can detect rise or fall in ctDNA to help determine if the treatment is effective.
• Predict the risk of recurrence. In breast cancer, the Oncotype DX® breast cancer assay helps calculate the likelihood of recurrence. This assay helps determine which women will benefit from chemotherapy after surgery. For women with DCIS, this test can help forecast if she will benefit from radiation after DCIS surgery.

Couple Of Vials Of Blood

Can liquid biopsies detect a recurrence?

Due to the limitations of CT scans, tiny new tumors that recur aren’t visible on a CT scan. However, these tiny tumors may already be shedding circulating tumor DNA into the bloodstream. In theory, a liquid biopsy could detect these minuscule amounts.

However, the technology has not reached that stage yet. The thought is tantalizing that a simple blood draw could tell us if we’ve experienced a recurrence. But several obstacles stand in the way. Because the amount of ctDNA that is shed is minuscule in a tiny, newly-occurring recurrence, the liquid biopsy to obtain a sampling for this purpose would require intense study driving up the cost to potentially prohibitive levels.

Yet, the potential exists for liquid biopsy technology to evolve over the next five years so that it is easier to detect recurrences through ctDNA and that the costs will come down so that it is more cost-efficient than CT scans, bronchoscopes, and other imaging techniques.
Some cancer types shed more ctDNA than other types of cancer — breast, colorectal, and lung cancer tumors seem to shed more ctDNA than other types of cancer. As research continues, more tumor types should be added to the list of potential cancers where liquid biopsies can be used.

How many companies offer liquid biopsies, and are they covered by insurance?

There are some commercially available liquid biopsy companies. Your oncologist will select the particular test most appropriate for you.
Some liquid biopsies are covered by private insurance and Medicare, while many insurance companies don’t provide coverage. Your healthcare team will help you navigate through insurance issues if a liquid biopsy is necessary.

Estimates suggest that liquid biopsies will be a $10-$20 billion portion of healthcare expenditures in 2020. Companies are investing heavily to develop this cutting-edge cancer technology further. The hope is that as costs for liquid biopsies decline that liquid biopsies will offer a less expensive and less invasive way of monitoring patients during and after treatment.

Genotyping And Sequencing

Here are some of the commercially-available liquid biopsies (arranged alphabetically):

• Cancerintercept (Pathway Genomics)
• Cobas EGFR Mutation Test v2 (Roche)
• FoundationACTTM (Foundation Medicine)
• Grail (Grail Bio, an Illumina spinoff)
• Guardant360 (Guardant Health)
• myRisk (Myriad Genetics)
• OncocEE (
• Oncotype SEQ (Genomic Health)
• PlasmaSelect-R (Personal Genome Diagnostics)

So WhatNext?

The future is almost here. At some NCI-designed cancer centers, oncologists are already using liquid biopsies for monitoring response to treatment and to detect mutations in patients. The experience of these National Cancer Institute (NCI)-designated treatment centers will help formulate guidelines for the use of liquid biopsies within the near future.

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