Presence of ctDNA and CTCs and Prediction of Disease Recurrence in Patients With Triple-Negative Breast Cancer

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In a preplanned secondary analysis of the BRE12-158 trial published in JAMA Oncology, Milan Radovich, PhD, and colleagues found that the presence of circulating tumor DNA (ctDNA) and circulating tumor cells (CTCs) in the plasma of women who have received neoadjuvant treatment for stage I, II, or III triple-negative breast cancer is an indicator of disease recurrence and disease-free survival.

Milan Radovich, PhD

Milan Radovich, PhD

These findings were also presented at the 2019 San Antonio Breast Cancer Symposium.


Researchers analyzed plasma samples taken from the blood of 196 women as part of a preplanned secondary analysis the phase II BRE12-158 trial. In the trial, patients with early-stage triple negative breast cancer who had residual disease after neoadjuvant chemotherapy were randomly assigned to undergo postneoadjuvant genomically directed therapy vs physician’s choice of therapy.

CtDNA was sequenced using the FoundationACT or FoundationOneLiquid Assay, and CTCs were detected using an epithelial cell adhesion molecule–based, positive-selection microfluidic device.


The team found that the detection of ctDNA was significantly associated with poorer outcomes on three important measures for patients: distant disease–free survival, disease-free survival, and overall survival.

At 2 years after surgery and chemotherapy, distant disease­–free survival for women with the presence of ctDNA in their blood was 56% vs 81% percent for women who had no ctDNA detected. 

Patients with the presence of both ctDNA and CTCs at 2-year follow-up had a distant disease–free survival probability of 52% vs 89% in individuals who were negative for both markers.

“Since uncovering these findings in women diagnosed with triple-negative breast cancer, we have learned that others are applying this stratification of patients based on ctDNA and CTCs to other cancers, including breast and colon [cancers],” said Dr. Radovich.

The study authors concluded, “In this preplanned secondary analysis of a randomized clinical trial, detection of ctDNA and CTCs in patients with early-stage triple-negative breast cancer after neoadjuvant chemotherapy was independently associated with disease recurrence, which represents an important stratification factor for future postneoadjuvant trials.”

Next Steps

These findings will be the focus of the PERSEVERE study, which will stratify women with triple-negative breast cancer based on their ctDNA status and assign them a targeted therapy matched to genomic sequencing results. The study is powered to help discover a personalized therapy for patients at high risk for relapse and for whom no treatments currently exist. More information about the PERSEVERE study will be available soon.

Disclosure: For full disclosures of the study authors, visit

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®.