Abstract
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Liquid biopsies screen blood samples for DNA and protein markers found in the blood. This is far less invasive than a traditional biopsy and can be analyzed in a lab without costly procedures. There are a number of researchers studying the potential use of liquid biopsy in conjunction with and possibly in lieu of traditional biopsies.
In 2016, the Food and Drug Administration approved its first blood test to detect mutations associated with non-small cell lung cancer (FDA, 2016). This technique has come a long way, and in a recent study, use of a “universal” liquid biopsy called CancerSEEK showed promising results. In this study, CancerSEEK tested for eight common cancers (ovary, liver, stomach, pancreas, esophagus, colon, lung, and breast) using a panel that included >2,000 positions in 16 different genes, as well as eight protein markers. While better at detecting stage II and III cancer, 43% of stage 1 cases were accurately detected. Some cancers had a higher rate of detection than others, with CancerSEEK almost always detecting cases of ovarian or liver cancers, but with less success detecting breast or lung cancers. In addition to identifying patients with one of the eight types of cancer accurately, only 7/812 healthy patients received a false-positive. However, it remains unclear if those individuals are true false-positives or if they have cancer that is yet to be detected through traditional methods (Cohen, 2018). It also remains unclear how accurate this test will be in less healthy populations, since proteins used in CancerSEEK can also be found in people with inflammatory conditions such as arthritis (Kaiser, 2018).
In this study, researchers were even able to determine location, a particularly elusive aspect of liquid biopsy cancer detection, using an approach called machine learning. Using nothing more than the test results, a computer was able to localize the likely origin to two anatomic sites in a median of 83% of patients and to localize to a single site in a median of 63% of patients, most of which was derived from the protein markers, since cancer DNA mutations are not tissue specific (Cohen, 2018).
Many articles mention the implications liquid biopsies may have on patients who have been diagnosed with cancer or are in remission, and even comment on the future potential to screen all patients (NCI, 2017). National Institutes of Health Director Francis Collins (2018) has said, “If all goes well, the hope is it may one day be as easy for primary care doctors to order a blood test to screen for many common forms of cancer as it now is to order a test for blood glucose or cholesterol.”
However, one group seems to be missing from the dialogue. High-risk individuals, namely those with genetic predispositions to cancer, are an untapped resource that could join the conversation around the potential of liquid biopsy for early detection. There is huge potential for liquid biopsy to monitor these individuals who, despite living a healthy life, carry a huge weight of worry and deep sense of helplessness about a cancer diagnosis that may never come. A woman with a BRCA mutation who has an increased risk of breast or ovarian cancer could perhaps augment watchful waiting's more invasive monitoring with a liquid biopsy.
A potential challenge with liquid biopsy is the test potentially picking up small tumors that will never grow large enough to cause problems (Kaiser, 2018). Within a population with a genetic predisposition, you may not run into the same challenges, since predisposition would warrant follow-up on all identified tumors and would be less likely to result in over-diagnosis or over-treatment.
It would be interesting to see a long-term study that compares the results of liquid biopsy in individuals with a genetic predisposition and no history of diagnosis over the course of a few years, while maintaining current means of screening. Such a study could not only shed some light on the ability of liquid biopsy to detect early stage cancer accurately, but also could potentially save lives with early detection in a high-risk community.