Hallmark Circulating Tumor-Associated Cell Clusters Signify 230 Times Higher One-Year Cancer Risk

We have previously shown that circulating ensembles of tumor-associated cells (C-ETACs) are a systemic hallmark of cancer based on analysis of blood samples from 16,134 individuals including 10,625 asymptomatic individuals and 5,509 diagnosed cases of cancer. C-ETACs were ubiquitously (90%) detected across all cancer types and were rare (3.6%) among the asymptomatic population. Consequently, we hypothesized that asymptomatic individuals with detectable C-ETACs would have a definitively elevated risk of developing cancer as compared with individuals without C-ETACs. In the present manuscript we present 1-year follow-up data of the asymptomatic cohort which shows that C-ETAC positive individuals have a 230-fold (P < 0.00001) higher 1-year cancer risk as compared with individuals where C-ETACs were undetectable. Simultaneously, we also expanded the study to include 4,419 symptomatic individuals, suspected of cancer, prior to undergoing an invasive biopsy for diagnosis. C-ETACs were detected in 4,101 (92.8%) of these 4,419 cases where cancer was eventually confirmed. We conclude that detection of C-ETACs can identify patients at risk of cancer and can be reliably used to stratify asymptomatic individuals with an elevated 1-year risk of cancer. PREVENTION RELEVANCE: The study evaluated a blood test that can determine if healthy ('asymptomatic') individuals without a history of cancer have an increased risk of developing cancer within the next one year. This test can significantly minimize radiological or invasive screening in the majority individuals who do not have any increased risk.