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by Dr. C.H. Weaver M.D. Updated  8/2022

The term liquid biopsy is being used with increased frequency within the context of cancer treatment. What, exactly, is a liquid biopsy, and how is it different from other biopsies?

What Is a Biopsy?

The National Cancer Institute defines biopsy as “the removal of cells or tissues for examination by a pathologist.”1 To establish a diagnosis of cancer, all patients must first undergo a biopsy. This is essentially the only way to truly distinguish whether a tumor or atypical cells are the result of a benign condition or of cancer.

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Historically, biopsy procedures used to obtain a tissue or cell sample were either an incisional biopsy, in which a sample of suspicious tissue is removed; an excisional biopsy, in which the entire area of suspicion is removed; or a needle biopsy, in which a needle is used to remove fluid or a small sample of tissue. Needle biopsies can be performed with a thin needle, referred to as a fine-needle aspiration biopsy, or a wide needle, referred to as a core biopsy. Although these methods are still standard, liquid biopsies are an area of extensive research and are proving to have the potential to become a critical tool for patients with cancer.

How Are Liquid Biopsies Different?

A liquid biopsy is performed by testing a sample of blood for the presence of circulating cancer cells, known as circulating tumor cells. Perhaps more importantly, samples of blood obtained from a liquid biopsy can also be tested for cell-free tumor DNA (cfDNA), which are fragments of DNA shed by cancer cells into a patient’s bloodstream.

Because cancer cells are constantly “shedding” parts of their DNA, specific genetic mutations (alterations) within these pieces of DNA can provide invaluable information to healthcare providers and ultimately help guide optimal treatment options for each patient.

Importantly, the bits of cf DNA obtained from a liquid biopsy can provide information to healthcare providers in the following areas:

  • If or to what extent the cancer is responding to treatment
  • Optimal treatment options specific to the DNA mutations of the cancer cells
  • Earlier detection of cancer compared with standard screening measures
  • Molecular and genetic real-time changes occurring in a patient’s cancer cells in response to treatment and growth

Guiding Treatment Options

Treatment for cancer is rapidly becoming more individualized and targeted toward specific molecular characteristics and/or genetic mutations of a patient’s cancer cells. Because these individualized treatment approaches rely completely on very specific characteristics of cancer cells, identification of these characteristics from liquid-biopsy samples can be an important determinant in the choice of medication most likely to be effective for each individual. Furthermore this information can possibly eliminate treatment choices to which the cancer cells will likely not respond.

Over time cancer cells tend to develop different genetic mutations in response to treatment and/or as they spread and grow. Therefore multiple samples obtained from liquid biopsies throughout the treatment period can help healthcare providers understand whether the patient’s cancer cells are continuing to respond to treatment, as well as the ways in which the cells are changing. This allows for ongoing modification of treatment regimens based on identified changes of the cancer cells. This is in contrast to other types of biopsies, which are performed prior to initiation of treatment for a “onetime snapshot” of a cancer’s characteristics and which don’t allow for continued monitoring of changes over time within cancer cells’ DNA.

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Potential for Early Detection

Liquid biopsies have the potential to detect cancer cells in a patient’s body at an earlier stage than many standard screening methods. This may play an important role in both initial screening measures for early detection of cancer, as well as early detection of a cancer recurrence.

To produce the DNA detectable by a liquid biopsy, often fewer cancer cells are required than the number needed for a scan or other laboratory method. Because earlier cancer detection tends to be associated with improved patient outcomes, liquid biopsies may ultimately play a critical role in how cancer screening is performed.

An Easier, Less-Invasive Biopsy

Biopsies that require the removal of tissue samples are often associated with pain during and after the procedure, the potential for infection, the potential for scarring, required medication, anxiety, and the need for extended periods of time in the clinic.

Scans used for detection of cancer recurrences sometimes require intravenous medication, dietary changes prior to the test, significant time for the scanning process, and significant financial resources.

A liquid biopsy can circumvent many of these issues, as all that is required from the patient is a blood sample.

Moving Forward

The cornerstone of cancer treatment has undergone a rapid and monumental shift toward targeting very specific molecular and genetic characteristics of cancer cells. Liquid biopsies can quickly identify these targets to determine which medications will be most effective in treating an individual’s cancer. They can also offer real-time monitoring of genetic changes in cancer cells that invariably occur over time. This innovation allows providers not only to move ahead with timely implementation of effective treatment according to identified genetic characteristics but also to avoid treatment that is not likely to be effective or to which the cancer cells have developed resistance.

Furthermore, the use of liquid biopsy reduces burdensome time and financial commitments associated with scans, invasive biopsies, and other laboratory procedures; it can potentially identify earlier stages of initial cancers and sites of recurrences; and it does not carry the risk of pain, scarring, anxiety, additional medication, and potential for infection associated with other, earlier methods of biopsy.

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Research is continuing to standardize liquid biopsies, as well as to expand the understanding of how the information obtained from liquid- biopsy samples can truly guide continuous treatment decisions for those affected by cancer.


National Cancer Institute Dictionary of Cancer Terms, s.v. “biopsy,” accessed September 28, 2016, .

Charles H. Weaver, MD, founded, one of the first patient-focused cancer web portals, in 1997 and serves as executive editor of Women. Dr. Weaver trained at the University of Washington, the University of Pennsylvania, the National Institutes of Health, and Fred Hutchinson Cancer Research Center. He has authored more than 75 articles in major medical journals, including the Journal of Clinical Oncology, Blood, Cancer, Bone Marrow Transplantation, and the New England Journal of Medicine.

Jennifer Murar-Maxon, RN, BSN, has 20 years’ experience in the science and medical fields of oncology. She has worked in a laboratory setting with a focus on understanding the molecular biology of cancer cells, as a hospital oncology nurse, and as a medical writer for physicians, nurses, and patients—all in the field of oncology.