Liquid Biopsies Read Cancer’s Genomic ID Card

Part I: Spare the Incision: Possibilities with High-Tech Blood Tests
May 26, 2017
Lada Krilov, PhD, ASCO Staff

ASCO Perspective

“For patients with tumors inaccessible or impractical for tissue biopsy, liquid biopsy represents an excellent alternative for ascertaining genomic data. Furthermore, serial sampling is far more feasible with liquid biopsy as compared to tissue biopsy, the latter exposing the patient to risks including infection and bleeding.”

  • Sumanta Pal, MD, ASCO Expert

Nearly every patient with cancer will go through a biopsy at some point. In fact, tumor biopsy is the main way doctors confirm a suspected cancer diagnosis. Pathologists look at the biopsy sample under a microscope to determine the type of cancer and how aggressively it may grow. These two pieces of information are critical for treatment planning.

More and more patients today also receive genomic or molecular testing of the biopsied tissue. Such testing can reveal genetic changes. For some cancers, physicians match targeted treatments to these specific tumor characteristics. Growing evidence shows that patients who receive such personalized “treatment matching” fare better.

Unfortunately, not all patients who could benefit from genomic testing are able to have the test. After diagnostic pathology testing, there is often not enough biopsied tissue left for genomic testing, or the quality of the sample is inadequate.

In addition, depending on the patient’s general health and the location of the tumor in the body, a tumor biopsy may not be safe or even feasible. Tumors in the liver, pancreas, and lungs can be particularly difficult to reach safely. In the absence of information about the key genomic changes in the tumor, it is difficult to personalize treatments to achieve the best result. 

Fingerprinting Tumors in Real Time

What if we could glean important cancer genomic information from a blood test? Emerging technologies nicknamed “liquid biopsy” may allow doctors to do just that and more. A promising approach involves testing so-called circulating cell-free circulating tumor DNA (ctDNA), tiny pieces of genetic material that tumor cells shed into the bloodstream.

Genomic changes can differ between various areas within a tumor, as well as among the different organs where the cancer has spread. A ctDNA test provides a “summary report” of all the genomic abnormalities in the primary tumor and metastases. In contrast, a tissue biopsy, which typically takes only a small piece of the tumor, sometimes misses key genetic changes that fuel cancer growth.

Another advantage of ctDNA testing is its ability to capture genomic changes in real time. Genomic changes evolve as the cancer grows and spreads. New changes may lead to cancer recurrence or resistance to treatment. A liquid biopsy test requires only a simple blood draw. It is generally safe and convenient to repeat, allowing doctors to keep easier track of new mutations and plan for targeted treatment.

Guidelines recommend that patients with melanoma and breast, non-small cell lung, and colorectal cancer have repeated biopsies each time the cancer recurs or grows despite treatment, so that treatments are adjusted to match the evolving genomic makeup of the tumor. However, it is not always possible to perform repeated tumor biopsies because of risks complications such as bleeding and infection.

Thus, for many patients targeted treatment decisions are made based on results from initial genomic testing, which can be years old by the time the cancer recurs, not adequately reflecting the current genomic makeup of the tumor. For instance, breast cancers that are initially positive for HER2 can later become HER2 negative, making earlier treatments ineffective.

The most widely used commercial ctDNA test (Guardant360) screens for various types of abnormalities in up to 73 cancer-related genes using a new, next-generation sequencing technology called “digital sequencing.”1 The blood test is recommended in place of invasive tumor biopsy for patients with advanced cancer who have insufficient initial biopsy sample for genomic testing, or the sample is unobtainable or uninformative. The test may also be used to test for new genomic changes at the time the cancer recurs or worsens despite treatment, enabling doctors to switch to a different targeted therapy, as needed.

To learn about early results from real-world applications of ctDNA testing, read Part II of this article series.


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