As if a possibly cancerous tumor weren’t scary enough, the word biopsy can strike additional fear because of the testing process itself, which often involves using a long needle to remove cells from a tumor or even surgery. Thankfully, advances in cancer research are leading to newer and more informative ways of finding out the nature of a tumor—blood tests. There are already a few types of such blood tests, and while they all hunt for secrets in patients’ DNA, there are differences that you should be aware of…

Liquid Biopsy

The term liquid biopsy was introduced about 10 years ago. It’s a way of getting information about a cancer from a blood test (the “liquid”) instead of tissue from the tumor itself. When cancers grow or break down, they shed whole cancer cells, proteins, cell fragments or fragments of cancer DNA into the blood. The blood sample taken for a liquid biopsy will have the tumor’s cell material and DNA.

A liquid biopsy has many advantages over a tissue biopsy. Different areas of a cancer may have different gene mutations, but a tissue biopsy tells you about only one small area. A liquid biopsy captures genetic information from all areas. Plus, the test is less invasive and less expensive and has a lower risk for pain, bleeding and infection.

Examples of liquid biopsy include the well-known prostate-specific antigen (PSA) test for prostate cancer…the carcinoembryonic antigen (CEA) test for breast, ovarian and colon cancers…the CA 125 for ovarian cancer…and CA 15-3 or CA 27.29 for breast cancer. However, these are all proteins related to cancers that are found in the blood. More recently, scientists have been able to detect and characterize actual tumor DNA by looking at genetic mutations in circulating, cell-free DNA, which is now called circulating tumor DNA, or ctDNA. While you might hear more about its potential, ctDNA testing is still in the early stages, confined mostly to clinical trials.

The main indication for any liquid biopsy has been that when taken over time, serial samples can help determine whether cancer treatment is working. The latest advances in blood testing are starting to guide treatment before it is even started. In 2016, the FDA approved a liquid biopsy test for ctDNA called the cobas EGFR Mutation Test to help guide treatment for the advanced lung cancer called non-small cell lung cancer. This test can be used to direct treatment to a specific type of antineoplastic therapy with a monoclonal antibody directed against EGFR. Other cancers where liquid biopsy may soon be approved to direct treatment are colon, breast and melanoma. It is even hoped that doctors may one day be able to screen for many cancers in a single blood sample.

Germline Testing

“Germline” mutations are DNA mutations in genes that normally prevent cancer development that are inherited. Inherited inactivating mutations in these “cancer susceptibility genes” explain why breast, ovarian, colon and prostate cancers run in families. Having a germline mutation (which would appear in every cell of your body, not only in areas susceptible to tumors) makes it harder for your cells to repair errors in DNA, which allows cancer to develop.

Screening blood tests that reveal germline mutations can reliably predict a higher risk for cancer. If one family member tests positive for a germline mutation, other members can be tested to find out whether they’re at very high risk for the cancer as well.

One of the best-known examples of a germline mutation is the BRCA genes. Women who have a strong family history of breast cancer and who test positive for BRCA have such a high risk for breast and ovarian cancer that they may elect to have their breasts, and also their ovaries, prophylactically removed before cancer has a chance to develop. Another example is the CDH1 gene mutation, which has a high prediction rate for deadly stomach cancer. Finding that mutation during a screening germline test gives patients the opportunity to consider having their stomach removed prophylactically.

Germline testing can also drive treatment decisions. For instance, colon, prostate and/or ovarian cancers in people with BRCA can be treated with a type of chemotherapy called a PARP inhibitor that works only in patients with BRCA mutations. These drugs have been principally tested in patients with germline BRCA mutations, but there is evidence that in some patients who have not inherited abnormalities in BRCA 1 or 2, the cancer itself may “knock” the gene out. PARP inhibitors may also work in these patients as well. Because of this, there is increasing discussion among experts to test both the germline DNA (which can be done by sequencing DNA from any cell in the body, such as white blood cells or cells lining the inside of the mouth) as well as tumor DNA (such as can be determined in a liquid biopsy).

Newer advances include testing for the cancer gene TP53, which makes it hard to repair radiation damage. Any cancer patient with this gene should avoid radiation treatment.


Researchers are currently examining how to make ctDNA results more reliable and useful. One problem is that while ctDNA testing may find genetic defects linked to cancer, it may not be able to tell exactly where or what type of cancer the defects came from.

Another hurdle to overcome is that genetic defects can be found in cells that are not cancer. For example, when white blood cells die, they can shed the same genetic defects as some cancer cells, but they will never become cancer.

One advance is taking place at Johns Hopkins where researchers developed CancerSEEK, a ctDNA test to look for proteins associated with the eight types of cancer responsible for 60% of cancer deaths in the US—breast, colorectal, esophageal, liver, lung, pancreatic, stomach and ovarian. By narrowing the focus from all types of cancer to these eight, they were able to limit the number of false-positives. If the results of their 1,005-patient study can be replicated in a larger study currently under way, it’s possible that the test could one day be as easy to get at your doctor’s office as a blood test for cholesterol.

Note: As amazing as blood biopsies are, it’s unlikely that they will completely replace all need for traditional biopsies in the near future, but they are already offering new insights into identifying and treating many cancers.

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