Circulating Tumor DNA in Breast Cancer: Clinical Utility and Limitations

In an interview with Targeted Oncology®, Stefania Morganti, MD, PhD, research fellow at the Dana-Farber Cancer Institute, addressed the current clinical utility and inherent limitations of using circulating tumor DNA (ctDNA) for minimal residual disease (MRD) detection in early-stage breast cancer.

A primary concern is the high risk of false-negative results due to the potentially very low amounts of ctDNA present in this patient population. Clinicians must stress this limitation to patients, according to Morganti, highlighting that a negative result may not equate to the absence of disease. Furthermore, the limit of detection varies significantly across different ctDNA assays. Tests with a lower limit of detection offer a decreased chance of a false negative, while those with a higher limit of detection increase the uncertainty regarding true disease status.

Crucially, routine clinical use is not currently recommended because almost all supporting data is retrospective. There is a significant absence of prospective clinical trials demonstrating that using ctDNA to guide treatment decisions translates to improved long-term patient outcomes.

However, the existing retrospective data strongly indicates the prognostic power of ctDNA. Patients who test MRD-positive (especially those persistently positive across multiple time points) face a substantially higher risk of disease recurrence compared to those who remain ctDNA-negative.