Time-dependent recurrence risk stratification after neoadjuvant chemotherapy for risk-adapted surveillance in breast cancer.

Abstract

e12672 Background: Post-treatment surveillance after neoadjuvant chemotherapy (NAC) is largely uniform and does not account for time-dependent recurrence risk. Although pathologic complete response (pCR) is associated with a favorable prognosis, recurrence still occurs in a subset of patients, with substantial heterogeneity in timing. We aimed to characterize dynamic recurrence risk after NAC to inform risk-adapted surveillance strategies. Methods: We retrospectively analyzed 2,331 patients with stage I–III breast cancer treated with NAC followed by surgery between 2005 and 2023. Disease-free survival (DFS) was the primary outcome. Conventional Cox proportional hazards models and flexible parametric survival models were used to evaluate time-dependent effects of clinicopathologic factors. Separate analyses were performed for patients who achieved pCR and for those with residual disease to identify clinically relevant risk windows. Results: Overall, 947 patients (40.6%) achieved pCR. Across all molecular subtypes, pCR was associated with significantly improved DFS; however, recurrence events occurred even among pCR responders. Among patients achieving pCR, baseline nodal positivity was associated with a delayed but progressively increasing risk of recurrence, with clinical significance beyond 3 years of follow-up. In contrast, patients who were node-negative at baseline and achieved pCR exhibited consistently low recurrence risk over time. Among patients with residual disease, high tumor proliferative activity (Ki67) conferred a pronounced early recurrence risk within the first two years after surgery, with diminishing impact thereafter. Conclusions: Recurrence risk after NAC is heterogeneous and evolves over time, even among patients who achieve pCR. Identification of distinct early- and late-high-risk windows challenges the adequacy of uniform post-treatment surveillance strategies. Aligning surveillance intensity with time-specific recurrence risk—rather than binary response status alone—may enable more precise and clinically meaningful survivorship care after NAC.