A team led by Mayo Clinic scientists has developed a patient-specific circulating tumor DNA (ctDNA) test that is reportedly sensitive enough to signal neoadjuvant treatment response in breast cancer.1 If the test is eventually validated, it could offer the first possibility of a liquid biopsy to guide decisions on subsequent local treatment options. Surgery – lumpectomy or mastectomy – following neoadjuvant treatment is the current standard of care for early and locally advanced breast cancer.

The use of liquid biopsies to guide surgical decision making after neoadjuvant treatment has proved elusive. Pretreatment ctDNA levels in breast cancer are already 25 times to 100 times lower than in the metastatic setting.2,3 They can become undetectable after neoadjuvant therapy in many patients with different cancer types.4–8

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The Mayo Clinic technique, named TARDIS (targeted digital sequencing), was sufficiently sensitive to predict the presence of residual disease in 17 of the 22 women with stage I to stage III disease who were treated with neoadjuvant therapy.

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“To be honest with you, I didn’t think it was going to be that good,” said study coauthor, Barbara Pockaj, MD, Mayo Clinic, Phoenix, Arizona. “Most liquid biopsies are very good with metastatic disease when there’s a burden of disease there, but this is in patients who are potentially cured, with a much smaller volume of disease. So to be able to identify the circulating tumor DNA in this subset of patients is critical, and really hasn’t been done well before.”

Using input DNA equivalent to a single tube of blood, the researchers determined that ctDNA levels predicted pathological status after neoadjuvant therapy. Median ctDNA levels were 5.7-fold lower in patients who achieved a pathological complete response (pathCR) compared with those who had residual disease (P =.0057).