MRD Testing Can Identify Breast Cancer Survivors at Higher Risk of Recurrence

Breast cancer survival rates continue to improve, but recurrence remains incurable and affects around 30% of patients. Some subtypes, like triple negative and HER2+, relapse within years, while ER+ cancers can recur decades later. Until now, there has been no way to identify survivors harboring dormant cells in real time or to intervene with treatments that could prevent relapse. Now, a new trial shows it is possible to detect these cells and clear them using repurposed drugs.

The trial was conducted by the Abramson Cancer Center of the University of Pennsylvania (Philadelphia, PA, USA) and Penn’s Perelman School of Medicine (Philadelphia, PA, USA). The approach builds on earlier research showing how dormant tumor cells, also known as minimal residual disease (MRD), can persist in patients after treatment. These “sleeper cells” evade imaging tests and may later reactivate, spreading metastatic breast cancer. Researchers identified pathways that allow such cells to survive and targeted them with existing FDA-approved drugs.

In preclinical mouse studies, two drugs that do not work against active cancers were highly effective against MRD, targeting autophagy and mTOR signaling. In the Phase II CLEVER clinical trial, 51 breast cancer survivors were randomized to receive either one of the drugs or both. Dormant tumor cells were cleared in 80% of participants, and after 42 months, only two recurrences were observed. Patients receiving both drugs achieved 100% recurrence-free survival.

The findings, published in Nature Medicine, highlight that treating patients during the sleeper phase may stop cancer from reemerging as metastatic disease. By using existing, affordable drugs, researchers demonstrated a feasible path to preventing relapse in breast cancer survivors. Larger trials, including the ABBY and PALAVY studies, are already underway to confirm and extend the CLEVER trial results. If successful, this strategy could replace “watch and wait” with proactive prevention of recurrence.

“The lingering fear of cancer returning is something that hangs over many breast cancer survivors after they celebrate the end of treatment,” said principal investigator Angela DeMichele, MD, MSCE, FASCO. “Our study shows that preventing recurrence by monitoring and targeting dormant tumor cells is a strategy that holds real promise.”

Related Links:
Abramson Cancer Center of the University of Pennsylvania
Penn’s Perelman School of Medicine