ctDNA: The next big leap in breast cancer care?

By Lisa Marie Basile | Fact-checked by MDLinx staff

Published March 12, 2025

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“ctDNA is here to stay, [and] I predict ctDNA will replace radiographic imaging… Our principles of adjuvant therapy are based on minimizing residual disease. We just haven’t been able to measure it until recently.” — Debu Tripathy, MD, Professor and Chair at the University of Texas MD Anderson Cancer Center

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This article is part of our Miami Breast Cancer Conference 2025 coverage. Explore more.

As the Miami Breast Cancer Conference came to an end Debu Tripathy, MD, Professor and Chair at the University of Texas MD Anderson Cancer Center, took the stage to discuss what he called an “emerging technology” in precision oncology: Circulating free tumor DNA—or ctDNA.

In metastatic breast cancer, physicians perform a liquid biopsy to attain ctDNA, which circulates in the bloodstream and originates in cancer cells and tumors. This is a non-invasive way to obtain “real-time tumor information to complement tissue biopsies, allowing for tailored treatment strategies and improved patient selection in clinical trials,” according to authors publishing in Nature.^[]

‘Can we make a difference?’

The quantity of ctDNA varies among individuals and depends on the type of tumor, its location, and for cancerous tumors, the cancer stage. “We know that over time patients do develop positive circulating tumor DNA—and they have worse outcomes in all subtypes. So can we make a difference?” Dr. Tripathy asked.

ctDNA, Dr. Tripathy said, can be used “in a research setting (with tumoral evaluation and mechanisms of resistance), in detection of germline mutations, and metastatic breast cancer.” In emergent areas, it can offer “early prediction of pathological complete response, detection of minimal residual disease and recurrence risk estimation, and tumor burden assessment."

The ability for ctDNA to offer a glimpse of minimal residual disease, he said, could help physicians know if a patient “may be in the process of recurrence. So we could give them a second adjuvant therapy or second chance."

Advancements in early detection

There is also a question around whether it can aid in early cancer detection—in mutations or methylation status. “There are already studies looking at that,” he said.

Researchers publishing in Nature Medicine, for example, looked at this possibility, concluding, “Next-generation liquid biopsy technologies that target the detection of cell-free DNA with fragments of circulating tumor DNA could be a game-changer in early cancer detection, but their adoption requires further clinical testing and consideration of harm.”^[]

The use of ctDNA hasn’t gained widespread traction—at least not yet, Dr. Tripathy said, but he noted ctDNA tests are now approved by the FDA and covered by Medicare.

“I predict ctDNA will replace radiographic imaging,” Dr. Tripathy said. “Our principles of adjuvant therapy are based on minimizing residual disease. We just haven’t been able to measure it until recently."

The question remains: How can physicians best utilize ctDNA findings? The answer remains to be seen. “Patients who had measurable tumor DNA had the worst outcomes, but there are patients who were negative or patients who were clear on the test. ctDNA can be prognostic, so what do we do with this information?” He said multiple trials are currently ongoing to try and answer this question.

Dr. Tripathy said that access to the original tumor tissues is necessary to really gain the information needed from the ctDNA, but AI tools are being used to help bridge this gap. But no matter what, he stressed, “ctDNA is here to stay.”

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