Game-Changer or Media Sensation?

A new blood test is offering hope of identifying early-stage breast cancer patients at risk of relapse after apparently successful treatment, on average, eight months before clinical relapse occurs. Understandably, news of this possible breakthrough has gained an immense amount of public interest, with headlines reporting on a “simple” blood test (1) which can “determine if your cancer will come back” and is set to make biopsy “unnecessary” (2) – but the reality isn’t so straightforward. We take a look at the science behind the headlines...

The study, conducted by researchers at The Institute of Cancer Research, London, UK, used personalized digital PCR (dPCR) for circulating tumor DNA (ctDNA) analysis. In a cohort of 55 women with early-stage breast cancer, massively parallel sequencing was used to characterize the mutations present in their individual tumor biopsies, and personalized dPCR assays for each somatic mutation were then used for “mutation tracking” – using serial samples following treatment to identify each patient’s specific mutations in their plasma (3). dPCR is a highly sensitive method, which can identify very small amounts of mutant DNA, making it an ideal approach for tracking tiny quantities of tumor DNA in the blood.

The results demonstrated the potential clinical utility of ctDNA analysis in this scenario: 19 percent of the patients had ctDNA present in their plasma just two to four weeks after cancer surgery, and this was found to be a significant predictor of early relapse. For patients who were assessed with “mutation tracking” at six-month intervals, 80 percent of patients had ctDNA present in their blood prior to relapse. In patients who didn’t have a recurrence of their cancer during the time of the study, 96 percent did not have ctDNA detected in a postsurgical sample or via mutation tracking. The method appeared to be effective in all breast cancer subtypes, but was particularly sensitive in ER positive cancer – a promising result.

However, there were clear limitations: this was a small study with only two years of follow-up, and there is as yet no information on how many of these patients might go on to relapse at a later date. It appears the test cannot spot brain metastasis – in three patients with cancer restricted to the brain, no ctDNA was detected, potentially because the blood-brain barrier prevented it from entering circulation.

The hope is that the earlier relapse is detected, the earlier treatment can begin, which could mean better outcomes for patients. But the relative expense and highly individualized nature of the test means that getting it to the clinic is unlikely to be quick or easy, and further validation is needed. “Ours is the first study to show that these blood tests could be used to predict relapse. It will be some years before the test could potentially be available in hospitals, but we hope to bring this date closer by conducting much larger clinical trials starting next year,” says the trial leader, Nicholas Turner.