Abstract PS2-10-12: Perioperative minimal residual disease monitering using a tumor-informed ctDNA assay in stage II-III breast cancer

Abstract Background Tracking minimal residual disease (MRD) via circulating tumor DNA (ctDNA) is associated with treatment efficacy and recurrence. This study presents perioperative tumor-informed ctDNA monitoring in stage II-III breast cancer (BC). Patients and Methods Patients with stage II-III BC were prospectively enrolled at Seoul National University Hospital (Feb 2023-Jul 2024). In the neoadjuvant chemotherapy (NAC) arm, whole blood (WB) was collected at seven perioperative points: baseline (N00), post-cycle 1 (N01), post-NAC (N03), 1-2 months (P00), 6 months (P01), 12, 24, and 36 months post-surgery (P02, P04, P06). In the adjuvant chemotherapy (AC) arm, WB was collected at P00, P01 or post-AC (P99), P02, P04, P06, and 48 months (P08). Plasma was analyzed using CancerDetect™ (IMBdx), a personalized tumor-informed MRD assay. Samples with ≥2 mutations were ctDNA+. Results Among 231 patients, 138 provided evaluable samples (130 in NAC). Median age was 51.5 (range 25-83). Subtypes included HER2+ (41.3%), TNBC (34.1%), HR+/HER2- (24.6%), with 59.4% stage II and 40.6% stage III. The median number of targeted variants was 56 (range 3-100), significantly higher in TNBC and HER2+ than HR+/HER2- (p<0.001).In NAC patients, ctDNA positivity was 80.6% (104/129) at N00, 36.5% (46/126) at N01, 20.2% (24/119) at N03, 12.5% (16/128) at P00/P01, and 8.7% (6/69) at P02. In AC-only patients, positivity was 25% (1/4) at P00, 12.5% (1/8) at P01/P99, 25% (2/8) at P02, and 50% (1/2) at P04.Multivariable logistic regression for baseline (N00) ctDNA+ showed associations with subtype (p=0.015), T stage (p=0.025), and histologic grade (p=0.040). ctDNA positivity at N00 was 90.7% in TNBC, 80.7% in HER2+, and 64.3% in HR+/HER2-. Median ctDNA concentration at N00 (PPM) was 5,660.5 in TNBC (range 21.5-270,615.4), 442.9 in HER2+ (3.5-40,818.3), and 184 in HR+/HER2- (8.8-84,892.3), with TNBC associated with significantly higher levels (p=0.015).The pCR rate in NAC arm was 45.0% (58/129). ctDNA positivity after NAC (N01) was 8.0% (4/50) in pCR patients vs 29.4% (20/68) in non-pCR (p=0.003). At the median follow-up of 523 days (range 255-876), five recurrences occurred. All 3 recurrences in the NAC group were ctDNA+ at N03 and non-pCR. Recurrence was significantly associated with ctDNA positivity at N01 (p=0.014) and N03 (p=0.024). ctDNA concentration at P00 (PPM) also significantly predicted recurrence (p=0.001). Conclusions Perioperative tumor-informed ctDNA monitoring reflects treatment response and risk of recurrence in stage II-III breast cancer. Both binary ctDNA status and quantitative concentration (PPM) demonstrate prognostic value at key clinical time points. Citation Format: J. AHN, J. Jung, Y. Cha, S. Heo, E. Kang, W. Chung, H. Kim, D. Bang, S. Song, H. Lee, W. Han, T. Kim. Perioperative minimal residual disease monitering using a tumor-informed ctDNA assay in stage II-III breast cancer [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 PS2-10-12.