Fig. 3: ctDNA predicts metastatic recurrence and refines risk stratification of breast tumors resistant to neoadjuvant therapy (NAT).

Kaplan–Meier estimates for 3-year distant recurrence-free survival (DRFS) rates were calculated in A patients stratified by residual cancer burden (RCB) class: RCB-0 (pathologic complete response), RCB-I (limited), RCB-II (moderate), and RCB-III (extensive); in patients with NAT-resistant tumors defined as RCB-II/RCB-III stratified by B ctDNA status at pretreatment (T0) or C ctDNA status post-NAT before surgery (T3); and D in all patients with RCB-II/RCB-III stratified by ctDNA dynamics or the timing of ctDNA clearance. Patients were grouped into persistent ctDNA-negative, ctDNA cleared at week 3 (T1), week 12 (T2), or post-NAT before surgery (T3), and no ctDNA clearance post-NAT before surgery. The p-values for the survival curves were calculated using the log-rank test. E Model discrimination was assessed using Harrell’s concordance index (c-index) to evaluate the prognostic performance of the risk models for predicting DRFS. The error bars represent the 95% confidence intervals (see Table 1).