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Abstract Background: Adjuvant therapy for early-stage breast cancer is currently stratified based on clinical risk factors, enhancing prognosis but leaving some patients at risk of recurrence. Circulating tumor DNA (ctDNA)-based minimal residual disease (MRD) detection aids in identifying recurrence risks and predicting prognosis. However, its utility in guiding postoperative systemic treatment remains unclear. This study seeks to employ longitudinal MRD monitoring to optimize adjuvant therapy strategies for early-stage breast cancer. Methods: Early-stage breast cancer patients naive to systemic anti-tumor therapy were enrolled. A tumor-informed MRD testing approach (Burning Rock Biotech, Guangzhou, China) was applied, in which pre-systemic therapy tumor tissues underwent whole exome sequencing (WES) to create personalized ctDNA detection panels (≤50 variants). Blood samples were collected 2-6 weeks postoperatively and before adjuvant systemic therapy for MRD testing. Patients with post-operative clinical high risk (pT>5cm, or pN+, or non-pCR after neoadjuvant therapy) or positive MRD received intensive adjuvant therapy, while those with low risk and negative MRD received standard adjuvant therapy. After treatment initiation, MRD testing and routine imaging evaluations were conducted every 3 months for up to 2 years or until tumor recurrence. If MRD remains positive or turns positive again during follow-up, an alternative intensive regimen (if available) will be adopted. No more than two intensive treatments are allowed. The primary endpoint is the 3-disease-free survival (DFS) rate. Results: This study enrolled 126 patients (94 TNBC, 21 ER+HER2-, 11 HER2+), including 33 stage I, 67 stage II, and 26 stage III cases. Based on clinical risk stratification, 71 patients were classified as clinical low-risk and 55 as clinical high-risk. The median follow-up was 726 days. The post-operative MRD was detected in 12.8% cases (16/125; 1 test failure), comprising 3 low-risk and 13 high-risk patients. Among post-operative MRD-positive patients, 87.5% (14/16) received dynamically adjusted intensive treatment. Of these, 13 converted to MRD-negative after longitudinal monitoring and personalized treatment, while 1 patient remained persistently MRD-positive. During follow-up, 8.3% (9/109) patients converted from post-operative MRD-negative to positive (3 low-risk and 6 high-risk). Of these patients, 1 with clinical high risk did not receive post-operative intensive treatment; 1 turned negative after conventional treatment without intensive treatment; 3 experienced a recurrence before the initiation of dynamically adjusted intensive treatment; 3 reverted to MRD-negative after dynamically adjusted intensive treatment; and 1 was newly detected as MRD-positive. In addition, 25% (9/36) patients with clinical high-risk and persistently MRD-negative status did not receive intensive treatment. Conversely, 12.3% (8/65) patients with clinical low-risk and persistently MRD- negative status received intensive treatment. Overall, 105 cases were included in the per-protocol analysis set, with a recurrence rate of 2.9% (3/105). The 2-year DFS rate was 96.5% (92.7%-100%). Conclusion: Preliminary findings support the feasibility of tailoring postoperative adjuvant treatment based on clinical risk and dynamic MRD monitoring. The follow-up is still ongoing. Clinical trial registration: NCT05345860. Citation Format: F. Ma, H. Ge, H. Mo, X. Sun, K. Zhao, L. Zhang, Y. Zhang, C. Li, G. Wang. Optimizing Postoperative Adjuvant Therapy for Early-Stage Breast Cancer by Combining Dynamic ctDNA MRD Monitoring with Clinical Risk Stratification: An Open-label, Multicenter, Prospective Study (AMENDER) [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 PS4-08-06.
Published in: Clinical Cancer Research
Volume 32, Issue 4_Supplement, pp. PS4-08