Liquid biopsies are a newer method of screening and have garnered a significant amount of attention in recent years. Their potential clinical impact as well as predictive and prognostic abilities greatly excites medical professionals. An educational session at the 2024 San Antonio Breast Cancer Symposium focused on liquid biopsies, their potential impact, what they can and cannot be used for, and future opportunities and challenges.
Ellen Landsberger, MD, MS, first set the stage of the discussion by speaking on the patient perspective of liquid biopsies, and what questions patient advocates may ask concerning circulating tumor DNA (ctDNA) use. Some of these questions may include the ability of ctDNA to replace traditional mammogram and tissue biopsy screening methods, as well as how ctDNA can be utilized to inform the optimal duration of hormonal therapy and chemotherapy.
Ben Ho Park, MD, PhD, spoke afterward, providing an overview of ctDNA and liquid biopsies, emphasizing their potential impact across various clinical areas. Dr Park defined ctDNA as DNA that is shed specifically by tumor cells into the circulation. Assays may be set up to look for different elements such as mutations/fusions, methylation, or RNA. He described looking for ctDNA in the bloodstream as looking for a needle in a haystack, noting the challenges in ctDNA detection due to its short half-life and low concentration in the bloodstream. However, though there is difficulty in detecting ctDNA, Dr Park does recognize that throughout the clinical treatment spectrum of cancer, there are areas where detection of cancer may be optimized if ctDNA were used instead of traditional detection methods. While ctDNA assays are rapidly evolving, there is still a set of unmet needs in this area, for example, the standardization of variables, amount of sample being collected for each test, and positive control standards.
Dr Park also focused on the current limitations of adjuvant therapy in addressing overtreatment and undertreatment, and how ctDNA may be able to help. He discussed the PREDICT-DNA trial, which investigated the use of ctDNA to assess pathologic response to treatment. Finally, Dr Park explored the potential of ctDNA as a predictive marker in metastatic disease, suggesting its use to monitor treatment response, prolong progression-free survival, and potentially augment or replace traditional response evaluation criteria.
Heather Parsons, MD, MPH, then discussed current ctDNA technologies and their application in guiding treatment decisions for both early and advanced breast cancer. She also highlighted that similar to the patient advocate discussion, there are a number of questions surrounding ctDNA use in its ability to replace traditional screening methods as well as its predictive, prognostic, and monitoring capabilities. Dr Parsons stated that a benefit of ctDNA assays is their ability to capture alterations from multiple metastatic sites, as well as being able to remove the need for a priori genetic information. She also emphasized the utility of comprehensive genomic profiling via ctDNA in advanced breast cancer, identifying specific genomic alterations that can guide FDA-approved therapies. Dr Parsons then shifted to the challenges and opportunities of using ctDNA in early breast cancer. Rather than specificity, the lower tumor fraction in early-stage disease necessitates highly sensitive tests to identify early disease and minimal residual disease (MRD). Serial sampling is currently necessary to achieve optimal sensitivity. An approach that has garnered success in boosting the sensitivity of these assays is taking a patient’s sample, identifying single nucleotide variants specific to that sample, and utilizing that to create a patient-specific tumor fingerprint panel. Dr Parsons presented data demonstrating the strong association between positive ctDNA tests after definitive treatment and metastatic recurrence, emphasizing the potential of ctDNA to predict recurrence and inform treatment decisions.
David Cescon, MD, PhD, presented on the potential of ctDNA to optimize treatment strategies and improve health outcomes. Dr Cescon highlighted using ctDNA as a predictive biomarker to identify patients who may benefit from specific adjuvant therapies. For example, in the IMvigor010 bladder cancer trial, patients in both the observation and atezolizumab groups were found to have poorer survival outcomes when ctDNA detection was positive. However, he emphasized the need for well-designed prospective trials to validate ctDNA's utility in guiding treatment decisions. Dr Cescon also explored the potential of ctDNA to avoid unnecessary adjuvant therapy, guide salvage therapy for recurrence interception, and guide treatment of MRD-escalation studies. While he agrees there are potential opportunities, there are still challenges and trials supported by high-quality data which are needed before ctDNA use in the preceding areas becomes regular practice.
The presenters collectively highlighted the exciting potential of ctDNA analysis via liquid biopsy in revolutionizing cancer care. The presentations emphasized the importance of rigorous research and clinical trials to validate the clinical utility of ctDNA across various applications, paving the way for personalized and effective cancer management strategies.
Landsberger E. ctDNA and the patient perspective. Presented at: San Antonio Breast Cancer Symposium. December 10, 2024; San Antonio, TX.
Park BH. Background: ctDNA and liquid biopsies. Presented at: San Antonio Breast Cancer Symposium. December 10, 2024; San Antonio, TX.
Parsons HA. Review of current technologies. Presented at: San Antonio Breast Cancer Symposium. December 10, 2024; San Antonio, TX.
Cescon D. From potential to practice: realizing the clinical utility of ctDNA. Presented at: San Antonio Breast Cancer Symposium. December 10, 2024; San Antonio, TX.