Innovative Approach to Preventing Breast Cancer Recurrence Using Dormant Cell Targeting

A groundbreaking clinical trial has demonstrated that it is possible to identify breast cancer survivors who are at a higher risk of recurrence due to dormant cancer cells, and to effectively eliminate these cells using existing FDA-approved drugs. Led by researchers from the Abramson Cancer Center of the University of Pennsylvania and their Perelman School of Medicine, this study was published in Nature Medicine. Despite advances in detection and treatment improving breast cancer survival rates, recurrence remains a significant concern. When cancer returns, especially in cases like triple-negative and HER2-positive subtypes, it often results in incurable metastatic disease, requiring lifelong treatment. Traditional methods lack the ability to detect dormant tumor cells, known as minimal residual disease (MRD), which can remain inactive for years before reactivating and causing relapse.

In the study, 51 breast cancer survivors were screened for MRD in their bone marrow. Patients found to have dormant tumor cells were enrolled in a randomized Phase II trial receiving either single or combination therapy with two drugs targeting autophagy and mTOR signaling pathways—mechanisms crucial for cell dormancy survival. After treatment, 80% of participants had their dormant cells eradicated; the three-year disease-free survival rate exceeded 90% with one drug and reached 100% with both. The findings suggest that monitoring and targeting these sleeping cancer cells could revolutionize post-treatment care.

Building on prior research, which revealed how dormant tumor cells can remain silent for decades, the study’s lead investigator, Dr. Angela DeMichele, highlighted the potential of this approach to intervene before dormant cells reactivate and develop into aggressive metastatic tumors. The experiments in mice confirmed that FDA-approved drugs, which are not effective against actively growing cancers, can successfully clear MRD by disrupting survival pathways.

This innovative strategy involves early detection of dormant cells, providing a window of opportunity to eliminate these cells before they cause relapse. The team is now advancing to larger ongoing trials, including the Phase II ABBY and PALAVY studies, to validate and expand these promising results. This research offers hope for a future where breast cancer recurrence can be significantly reduced by foreseeing and intercepting dormant cancer cells at the earliest stage.