Optimizing MRD Monitoring: Integrating Clinical and Genomic Insights

ctDNA monitoring has emerged as a highly sensitive tool for detecting molecular residual disease in early-stage breast cancer. One of the most clinically significant advantages of ctDNA is its ability to identify recurrence before symptoms or imaging abnormalities develop. When ctDNA becomes positive while imaging remains negative, this period (often referred to as the “lead time”) can extend up to 10 to 12 months, particularly in hormone receptor–positive, HER2-negative breast cancer. This window offers a critical opportunity to evaluate potential interventions, such as altering endocrine therapy or considering enrollment in clinical trials, even before overt metastasis occurs.

Despite its promise, ctDNA monitoring presents real-world challenges in clinical practice. Clinicians must carefully counsel patients before ordering ctDNA tests to ensure they understand the implications of both positive and negative results. A rising ctDNA level without radiographic confirmation can provoke anxiety and uncertainty. Clinicians typically respond by initiating imaging studies and repeating the ctDNA test to assess trends. Although there are no definitive guidelines on treatment based solely on ctDNA positivity, some oncologists consider changes in therapy for high-risk patients or refer them to ongoing clinical trials. This decision-making process is nuanced and must be tailored to the biology and risk profile of each patient.

Integration of ctDNA with traditional prognostic tools such as tumor grade, nodal status, and genomic assays (eg, Oncotype DX) enhances personalized treatment planning. For high-risk cases such as inflammatory breast cancer, node-positive disease, or high-grade tumors, ctDNA offers additional prognostic clarity. However, it is not yet considered a stand-alone tool for guiding chemotherapy decisions, especially in the absence of corroborating clinical or genomic data. As research evolves, the role of ctDNA is expected to expand, ultimately enabling more precise and proactive surveillance strategies in breast cancer care.