Liquid biopsies have emerged as effective diagnostic tools in disease monitoring and minimal residual disease detection. Circulating tumor DNA (ctDNA) was recently shown to be a predictor of poor response and recurrence in breast cancer. However, ctDNA shedding from breast tumors can rapidly decrease during treatment, resulting in reduced sensitivity in measuring early changes in tumor response or residual cancer burden (RCB) after neoadjuvant chemotherapy (NAC).