Optimizing a Surveillance Strategy to Tackle Breast Cancer Dormancy and Minimal Residual Disease
Abstract
While many patients who complete standard of care treatments are cured of early breast cancer, others will relapse at some point in their lifetime with incurable metastatic disease that has traveled to organs and bones. There is currently no testing available in practice to identify the patients who are cured and the patients who will relapse after completing treatment, so watchful waiting is the standard. Because there is no proactive way to monitor for disease before relapse, every person diagnosed with early-stage breast cancer carries the weight of anxiety and fear of recurrence. We also do not have a complete understanding of how lethal recurrence occurs or how to prevent it. Previous research into how early-stage breast cancer recurs as metastatic disease suggests that some tumors send seed cells (minimal residual disease or MRD) through the blood to the organs, bones, and bone marrow. These cells can either begin the process of becoming clinically detectable metastasis in organs or bones, or first enter a dormant or sleeping phase in niches throughout the body but primarily in the bone marrow. MRD that is circulating in the blood can be measured as circulating tumor cells (CTCs) or through fragments of tumor DNA (ctDNA). MRD that is dormant, including in the bone marrow, is measured as disseminated tumor cells (DTCs). DTCs can remain dormant for years to decades before they wake up (reactivate), begin dividing again, and reenter the bloodstream to travel to distant organs and bones. DTCs in the bone marrow of breast cancer survivors or CTCs/ctDNA in the blood are linked to a high likelihood of metastasis. The overarching challenges addressed by our research are to determine how breast cancer cells lie dormant for years and then re-emerge, and to determine how to prevent lethal recurrence. We have been working to address these challenges for several years through a translational clinical research platform (2-PREVENT) that screens patients to detect DTCs and ctDNA, and tests therapies to target and eliminate them. Our goal is to be able to monitor any patient who has completed treatment for early-stage breast cancer with highly sensitive tests for MRD, and to have treatments available that will eliminate MRD, resulting in a long-term undetectable state and subsequently preventing metastatic relapse and death. An important component of our work involves ongoing assessment of the psychological well-being and quality of life of patients participating in these MRD detection and treatment studies. While we have found that patients have been eager to contribute to research that may lead new interventions prior to recurrence and metastasis, we recognize the potential for harm that looking for and/or finding MRD can have. In all of our previous studies, we have been collecting patient reported outcomes (PROs) to understand whether proactive screening and long-term surveillance improves or worsens anxiety, fear of recurrence, intrusiveness of breast cancer into everyday life, or the overall emotional, physical well-being and quality of life. This Department of Defense (DOD) Clinical Research Extension Grant proposes to leverage four clinical trials (SURMOUNT, CLEVER, ABBY, and PALAVY, which were, in part, supported by previous DOD grants) to create a combined MRD surveillance cohort of patients we have previously screened for MRD, including patients who have been previously found to have MRD and have been treated on these clinical trials with therapies designed to eliminate the MRD. We anticipate enrolling approximately 224 patients in a long-term follow up surveillance study in which they will be clinically monitored for recurrence and tested for bone marrow DTCs and blood ctDNA every 6 months over a 3.5-year period. Participants will be scanned at the onset of participation to confirm that there is no evidence of metastatic disease. Participants with no evidence of metastatic disease on scans will
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jan 04, 2024
- Source ID
- HT94252310907
Entities
People
- Angela De Michele
Organizations
- United States Army
- University of Pennsylvania