Women who tested positive for circulating tumor DNA were at 12 times the risk of relapse of those who tested negative. Relapses could be predicted about 8 months before they became clinically apparent. [© prudkov/Fotolia]
Women who tested positive for circulating tumor DNA were at 12 times the risk of relapse of those who tested negative. Relapses could be predicted about 8 months before they became clinically apparent. [© prudkov/Fotolia]

Conducted repeatedly, a blood test capable of profiling circulating tumor DNA can track genetic changes that occur over time, picking up signs that a treated cancer—in this case, breast cancer—is about to return. The blood test, a so-called liquid biopsy, detects mutations in DNA shed by cancer cells, and it can be used to predict breast cancer relapse about 8 months before tumors become visible on hospital scans.

A liquid biopsy not only spares patients the invasive procedures needed to collect solid tumor samples, it can be repeated easily, catching key mutations that cancer accumulates as it develops and spreads. To create a liquid biopsy for breast cancer, scientists at the Institute of Cancer Research in London, developed a polymerase chain reaction (PCR) test that is sensitive to the sorts of mutations common to many types of breast cancer.

The researchers described their test August 26 in the journal Science Translational Medicine, in an article entitled, “Mutation tracking in circulating tumor DNA (ctDNA) predicts relapse in early breast cancer.” The article detailed the analysis of circulating tumor DNA in plasma, and showed how it may be used to enable monitoring for minimal residual disease (MRD) in breast cancer.

“In a prospective cohort of 55 early breast cancer patients receiving neoadjuvant chemotherapy, detection of ctDNA in plasma after completion of apparently curative treatment—either at a single postsurgical time point or with serial follow-up plasma samples—predicted metastatic relapse with high accuracy,” wrote the authors. “Mutation tracking in serial samples increased sensitivity for the prediction of relapse, with a median lead time of 7.9 months over clinical relapse.”

The authors added that analysis of ctDNA could define the genetic events of MRD, and that MRD sequencing predicted the genetic events of the subsequent metastatic relapse more accurately than sequencing of the primary cancer. They also pointed out that their test could identify the particular mutations likely to prove lethal to individual patients, raising the possibility of tailored treatments.

“We have shown how a simple blood test has the potential to accurately predict which patients will relapse from breast cancer, much earlier than we can currently,” said study leader Nicholas Turner, Ph.D., team leader in molecular oncology at the Institute of Cancer Research. “We also used blood tests to build a picture of how the cancer was evolving over time, and this information could be invaluable to help doctors select the correct drugs to treat the cancer.

“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.”

“We are moving into an era of personalized medicine for cancer patients,” added Paul Workman, Ph.D., chief executive of the Institute of Cancer Research. “This test could help us stay a step ahead of cancer by monitoring the way it is changing and picking treatments that exploit the weakness of the particular tumor. It is really fantastic that we can get such a comprehensive insight about what is going on in the cancer all over the body, without the need for invasive biopsies.”

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