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Circulating Tumor DNA Analysis for Detection of Residual Disease in Breast Cancer

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Key Points

  • In this first validation study, researchers analyzed 80 blood samples from 33 women with early-stage and locally advanced breast cancer. They found that the test was able to identify circulating tumor DNA in every patient before they started treatment.
  • The researchers did further blood tests on the 22 women who received treatment before their surgery, such as chemotherapy, radiotherapy, or hormone therapy. The test found that the concentration of circulating tumor DNA was lower for patients who had no breast cancer cells remaining at the point of surgery than for those who did.

Researchers have developed a new method for tracking residual disease in patients with breast cancer that could one day help doctors better tailor treatments and prevent unnecessary surgeries for some people with the disease. Findings were published by McDonald et al in Science Translational Medicine.

The new technique, called TARDIS (TARgeted DIgitial Sequencing), analyzes circulating tumor DNA. This test could one day allow doctors to use blood samples to continuously monitor how well breast cancer treatments are working, allowing them to personalize each patient’s treatment plan.

Lead study author Muhammed Murtaza, MD, PhD, of TGen, said: “Until now, blood tests for breast cancer have only been sensitive enough to reliably identify tumor DNA in people with advanced disease. We’ve shown that TARDIS is able to detect circulating tumor DNA at extremely low concentrations in the blood, opening up the possibility of monitoring patients with early-stage breast cancer to find out how their disease is responding to treatment.”

TARDIS looks for DNA sequences specific to each patient’s cancer. The test relies on a traditional biopsy of the tumor being taken first. The tumor DNA is then sequenced, and bioinformatics is used to identify mutations likely to be present in all cancer cells.

Methods and Findings

In this first validation study, researchers analyzed 80 blood samples from 33 women with early-stage and locally advanced breast cancer. They found that the test was able to identify circulating tumor DNA in every patient before they started treatment.

The researchers did further blood tests on the 22 women who received treatment before their surgery, such as chemotherapy, radiotherapy, or hormone therapy. The test found that the concentration of circulating tumor DNA was lower for patients who had no breast cancer cells remaining at the point of surgery than for those who did.

The researchers will now carry out a larger study, involving over 200 patients, to further validate the effectiveness of the test and to determine the concentration of circulating tumor DNA in the blood that could indicate to doctors that treatment prior to surgery has been successful. This could lead to clinical trials to find out whether the test can be used to reliably inform treatment decisions in a real-world setting.

The researchers hope the technique could also have applications beyond breast cancer and be used to monitor other types of cancer that are treated with drugs or radiotherapy before surgery.

Carlos Caldas, MD, of the Cancer Research UK Cambridge Centre, who contributed to this study, said, “This could be a game-changer. Instead of patients undergoing six to eight cycles of chemotherapy (15–21 weeks of treatment), after one or two cycles (3–6 weeks), we would use the TARDIS test to look for a significant drop in circulating tumor DNA. If a drop was not detected, the treatment could be stopped or changed.”

Dr. Caldas concluded: “Finding cancer DNA in the blood is like looking for a needle in a haystack. But by developing a test that’s unique to each patient, and looking for mutations present across the entire tumor, we’ve made it much harder for the circulating tumor DNA to hide, significantly increasing the chance of identifying cancer relapses earlier.”

Disclosure: For full disclosures of the study authors, visit stm.sciencemag.org.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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