ICARE Newsletter Spring 2023

Ask the Expert

The below question was addressed by Ben Ho Park, MD, PhD, who is the Director of the Vanderbilt-Ingram Cancer Center and a Professor of Medicine in the Division of Hematology and Oncology. If you have a question you would like addressed, please email the ICARE team at ICARE@vumc.org for consideration in future newsletters.


Q: As a 35-year-old woman with a BRCA1 mutation, I get breast MRIs and mammograms every year. I heard about additional blood tests that might be used to detect cancers early. Is this something that may be important for me to do?


A: These blood tests generally are talking about circulating tumor DNA (ctDNA) which comes from cancer cells and is released into the bloodstream. This is because as tumors get bigger, new cells grow as other cells die and get broken down, releasing their DNA into the bloodstream (meaning the ctDNA). For people at higher risk for cancer due to a mutation in an inherited cancer risk gene, the value of using ctDNA to screen for a new cancer is currently not known and should only be offered in the setting of prospective clinical trials. This is because the sensitivity, false-positive rates, false negative rates, and the positive predictive and negative predictive values of ctDNA tests for early-stage disease, are not yet well-established, particularly the negative predictive value, meaning if the test is negative, does this mean the patient is free of cancer? Moreover, even though the positive predictive value for some tests is quite good (meaning if the test is positive there is a good chance there is cancer somewhere), what we do not have is any data suggesting that acting on this information affords better outcomes. That’s the difference between what we call clinical validation (in this case positive predictive value has been validated) versus clinical utility, that is, knowing this is not helpful until we show that we can do something useful with this information.1-4 Additionally, the psychological impact of ctDNA testing also remains unknown. Currently, these types of tests have been shown to be useful in helping to diagnose certain tumors, guiding and monitoring tumor-specific treatment, and monitoring tumor-free periods.


1Duffy et al. Clin Chem Lab Med. 2021;59(8):1353-1361. PMID: 33856748.

2Offit et al. J Clin Oncol. 2023;41(1):11-21. PMID: 35944238.

3Hackshaw et al. Cancer Cell. 2022;40(2):109-113. PMID: 35120599.

4Raoof et al. Cancer Epidemiol Biomarkers Prev. 2022;31(6):1139-1145. PMID: 35320352.

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