Editor's Note: Liquid biopsy is not a new concept in the field of breast cancer, but its clinical applications continue to evolve, requiring fresh insights into the technologies, terminology, biomarkers, and future directions. On Tuesday, December 10 (Central Time), during the "Educational Session 2: Liquid Biopsy: MRD, ctDNA, and Monitoring Response to Treatment" at the 2024 San Antonio Breast Cancer Symposium (SABCS), experts discussed current liquid biopsy technologies and their optimal applications, including early disease detection, real-time monitoring, and predicting treatment responses.

“Liquid biopsy” is a broad term referring to the measurement of biomarkers in bodily fluids. Since the term was first introduced, it has encompassed various technologies, including the analysis of circulating tumor DNA (ctDNA) and cell-free DNA (cfDNA). Circulating tumor cells (CTCs) play a key role in metastasis formation, leaking from tumors into the bloodstream. This enables both molecular characterization of the tumor and personalized treatment monitoring. On the other hand, cell-free DNA refers to fragments of DNA from any cell in the body, released into the bloodstream upon cell death.

Dr. Adrian Lee, a professor of pharmacology, chemical biology, and human genetics at the University of Pittsburgh and UPMC Hillman Cancer Center, who chaired the session, remarked: “One challenge with liquid biopsy is the terminology. People often use ‘ctDNA’ and ‘cfDNA’ interchangeably, although they represent different concepts. One goal of this session is to standardize terminology to ensure we use the correct terms while deepening our understanding of the technologies employed.”

Dr. Lee emphasized that ctDNA analysis is one of the most transformative technologies in this field. Compared to imaging, ctDNA can detect early disease more effectively. Early detection is well-known to improve patient outcomes, as an increase in circulating tumor cells has been identified as a marker of advanced disease. Based on this correlation, the Centers for Medicare & Medicaid Services and some private insurers have approved reimbursement for certain tests to monitor disease recurrence or progression. However, guidelines do not recommend ctDNA monitoring due to a lack of robust supporting data.

Dr. Ben Park, Director of Precision Oncology at Vanderbilt University Medical Center, provided insights into early disease detection and nuances related to minimal residual disease (MRD). Meanwhile, Dr. David Cescon, a medical oncologist and clinician-scientist at Princess Margaret Cancer Centre, discussed applications in metastatic settings, including the use of MRD to guide decision-making.

Dr. Lee added: “Monitoring treatment response or resistance in real-time using ctDNA, and adjusting therapy accordingly, makes a lot of sense. This is what we should be doing, but the data supporting this approach remains limited.”

The more consistent use of ctDNA analysis is prompting deeper questions about patient care. For instance, should treatment be initiated for patients with evidence of MRD but no imaging-detectable disease? In such cases, premature treatment might severely affect quality of life and limit future therapeutic options.

Additionally, these tests and the detailed discussions around their results are increasing patients’ understanding of breast cancer. Dr. Heather Parsons, a medical oncologist at Dana-Farber Cancer Institute and assistant professor at Harvard Medical School, presented on current ctDNA and cfDNA technologies and their applications.

Patient advocate Dr. Ellen Landsberger, from New York, participated in a panel discussion with other speakers. Dr. Landsberger noted: “While cost remains a limitation, Dr. Lee expressed enthusiasm about the future of liquid biopsy in breast cancer research and treatment.”

“It’s exciting to see the rapid expansion of tests already in use,” Dr. Landsberger said. “Coupled with discussions on critical research findings expected to become pivotal in the next two to three years, both the speakers and I are enthusiastic about the content of this session, whether in setting standards or enhancing awareness of clinical utility.