Circulating Tumor DNA in Early Breast Cancer: A Review

Circulating tumor DNA (ctDNA) has emerged as a noninvasive biomarker with the potential to detect minimal residual disease (MRD), monitor treatment response, and identify recurrence (eg, molecular relapse) earlier than conventional clinical or imaging approaches. Although ctDNA-based MRD assays have demonstrated prognostic value in early breast cancer, their optimal clinical utility remains uncertain.

This review summarizes the current data on ctDNA MRD assays in early breast cancer. Although these assays have established analytical and clinical validity, their clinical utility remains uncertain. Dynamics of ctDNA during neoadjuvant therapy are associated with pathologic complete response and long-term outcomes. Following completion of curative-intent therapy, ctDNA positivity (eg, presence of MRD) is strongly associated with future distant recurrence. Similarly, the emergence of ctDNA during surveillance precedes the clinical diagnosis of overt metastatic disease. Although observational studies and meta-analyses have supported ctDNA as a complementary biomarker for established risk-stratification tools, evidence that demonstrates improved outcomes with ctDNA-guided management remains limited. Furthermore, the optimal timing and frequency of testing remain unknown, and studies comparing assays are lacking. Multiple ongoing prospective interventional trials are evaluating whether ctDNA-guided treatment escalation or de-escalation can improve patient outcomes and support the routine implementation of ctDNA assays in clinical practice.

ctDNA-based MRD assays hold promise for refining risk stratification, enabling earlier detection of recurrence, and informing treatment decisions in patients with early breast cancer, but clinical utility has not yet been demonstrated. Prospective trials are essential to determine whether ctDNA-guided interventions improve outcomes beyond standard management. Clinicians should understand the strengths, limitations, and evolving evidence base of ctDNA assays, as well as patient preferences, prior to incorporating them into patient care.