Abstract PS4-08-27: Risk of CNS relapse following pathological complete response to neoadjuvant chemotherapy

Abstract Background: Pathological complete response (pCR) after neoadjuvant chemotherapy (NAC) improved breast cancer (BC) outcomes. However, systemic therapy has limited central nervous system (CNS) penetration, and pCR may not predict reduced risk of brain metastases. We evaluated CNS recurrence patterns in early-stage BC patients with or without pCR after NAC. Patients and Methods: All consecutive stage I-III BC patients treated with NAC and surgery between 2007 and 2018 at A.C. Camargo Cancer Center were analysed. BC subtypes were defined by hormone receptor (HR) and HER2 status from pretreatment biopsies and pCR was defined as ypT0/is ypN0. The primary objective was the impact of pCR on the risk of CNS recurrences across BC subtypes. The secondary objectives were patterns of CNS recurrence (brain/leptomeningeal only versus synchronous systemic and CNS metastasis), CNS recurrence-free survival (CNS-RFS) and overall survival after CNS metastasis. Fisher`s Exact test and Pearson’s Chi-square test were used to evaluate differences in CNS across pCR status. Kaplan-Meier and regression analyses were performed. Two-tailed p-values<0.05 were considered significant. Results: Among 1147 patients treated with NAC, 537 patients had HR-positive/HER2-negative, 301 HER2-positive, and 309 triple-negative (TNBC) breast cancer. The median age was 45 years, most had ductal histology (84.7%), grade II (48.6%) or III (42.9%), and stage III (59.2%). Ninety-five percent received anthracycline+taxane NAC and all HER2-positive patients received at least 1 dose of (neo)adjuvant trastuzumab. Three hundred sixty-five (31.8%) achieved pCR - 59/537(11%) HR-positive/HER2-negative, 158/301(52.3%) HER2-positive, 148/309(47.9%) TNBC. CNS recurrence occurred in 72 (6.2%) patients, with no difference between pCR and non-pCR (4.7% vs. 7.0%, p=0.15). Among subtypes, there was no difference for HR-positive/HER2-negative (3.4% vs. 4%,p=1.0) and TNBC (5.4% vs 9.3%,p=0.2), but there was a reduction in risk for HER2-positive (4.4% vs. 14.7%, p=0.003). Isolated CNS relapse was more common among pCR, particularly in HER2-positive tumors (Table). CNS-RFS was improved in HER2-positive patients with pCR but not in other subtypes. Median overall survival after CNS relapse was 12 months, highest in HER2-positive patients (31 months) and lowest in TNBC (8 months). Multivariable analysis identified HER2-positive and TNBC subtypes and cN2-3 status as independent predictors of CNS recurrence. Conclusion: Pathological complete response was not associated with reduced CNS recurrence overall, but was linked to a lower risk of CNS relapse in HER2-positive breast cancer. Isolated CNS relapse was the predominant pattern, suggesting a sanctuary effect.Tailored surveillance strategies are needed in high-risk subtypes, particularly patients HER2-positive and TNBC regardless of pCR status. Citation Format: L. M. Leite, G. R. de Almeida, M. C. Tavares, M. G. Cesca, F. B. Campos, F. A. Oliveira, D. M. Dornellas, E. F. Saldanha, P. T. Guimarães, D. D. Arruda, M. S. Held, R. L. Viana, F. G. Moura, S. K. Loose, S. F. Silva, R. Pirolli, C. A. Fogassa, B. R. Mattos, S. M. Sanches, V. C. Cordeiro de Lima. Risk of CNS relapse following pathological complete response to neoadjuvant chemotherapy [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS4-08-27.