Editor’s Note: Liquid biopsy technologies are rapidly advancing, and circulating tumor DNA (ctDNA) monitoring has demonstrated enormous potential in precision treatment for breast cancer. During the Educational Session “Adjuvant Therapy for ER-Positive Breast Cancer” at the ESMO Breast Cancer Congress (ESMO BC), Professor Heather Parsons from the Fred Hutchinson Cancer Center delivered a presentation entitled “The Role of ctDNA Monitoring in ER+ Early Breast Cancer: Could It Change Practice?”In her lecture, Professor Heather Parsons systematically reviewed the current status and ongoing challenges surrounding ctDNA monitoring in ER-positive early breast cancer. She emphasized that ctDNA-based detection of molecular residual disease (MRD) is strongly associated with distant recurrence risk. However, because ER-positive breast cancer typically exhibits relatively low ctDNA shedding, serial monitoring is often required. Although retrospective studies have produced encouraging findings, prospective interventional evidence remains insufficient, and routine use outside clinical trials is not currently recommended.
Following the session, Oncology Frontier conducted an on-site interview with Professor Heather Parsons, who shared further insights into how ctDNA may eventually guide treatment escalation or de-escalation strategies, as well as the future direction of research in this field.
Oncology Frontier:
During this meeting, what topics did you focus on most in your presentation? What is the clinical significance of these approaches for precision treatment, and could you share some perspectives from your own clinical practice?
Professor Heather Parsons:
“My primary focus was on circulating tumor DNA, or ctDNA, sometimes also referred to as cell-free DNA (cfDNA). These are tiny fragments of DNA released into the bloodstream by cancer cells. Of course, our normal cells also release DNA fragments, but we now have highly advanced technologies capable of detecting the very small fraction of DNA that specifically originates from cancer cells.
This technology has several potential applications, but perhaps the most exciting—and also the most difficult to validate—is the concept of molecular residual disease, or MRD. MRD refers to microscopic residual cancer that remains in the body after initial treatment, which cannot yet be detected through imaging but may be identified through blood-based or other liquid biopsy approaches.
This has many potential implications in breast cancer. In hormone receptor-positive breast cancer, we have observed that the presence of ctDNA is strongly associated with distant recurrence, while ctDNA clearance appears to correlate with improved outcomes.
Our hope is that ctDNA could eventually serve as a biomarker to help determine which patients may benefit from more intensive therapy, while also identifying patients who may safely undergo treatment de-escalation.
The challenge we currently face is that although we have many very encouraging and exciting retrospective studies, we still lack sufficient prospective data to determine whether—and exactly how—we should use ctDNA and MRD to guide treatment decisions.
This is an area of research that I find particularly exciting. A number of interventional studies are currently ongoing, and at this meeting we also saw data presented from the TRAK-ER study entitled ‘ctDNA Detection Rates During Surveillance in High-Risk HR+/HER2-Negative Breast Cancer From the TRAK-ER Study’, presented by Niamh Cunningham.
The study showed some encouraging signals, but it also highlighted several important challenges. Many patients already had metastatic disease detectable on imaging at the time ctDNA positivity was identified. In addition, the frequency of ctDNA positivity in breast cancer remains extremely low, which is something we have consistently observed across multiple studies.
For these reasons, I believe there are still many unanswered questions that must be addressed before this technology can be routinely implemented in early breast cancer.
At present, ctDNA testing is already being used in metastatic breast cancer to guide treatment decisions, including the detection of biomarkers such as ESR1, PIK3CA, or alterations within the AKT pathway. However, when it comes to early breast cancer, we still have a considerable distance to go before this approach becomes part of standard clinical practice.”
Professor Heather Parsons
