Abstract 3260: Perioperative tumor-informed ctDNA monitoring for minimal residual disease in triple-negative and HER2-positive breast cancer patients

Introduction: Circulating tumor DNA (ctDNA) enables non-invasive monitoring in solid tumors. This study evaluates the prognostic and predictive value of minimal residual disease (MRD) detection using a personalized ctDNA assay during neoadjuvant chemotherapy (NAC) and post-surgical follow-up in triple-negative breast cancer (TNBC) or HER2-positive breast cancer (BC) patients. Methods: Patients with stage IA-IIIC TNBC or HER2-positive BC scheduled for NAC followed by curative surgery were prospectively enrolled. Peripheral blood samples (20 mL) were collected at three time points: before NAC (P0), perioperatively (pre- or one month post-operatively, P1), and one year post-operatively (P2). The CancerDetect™ assay (IMBdx, Inc.), a tumor-informed MRD test, identified patient-specific mutations (up to 100) through whole exome sequencing (WES) of tumor tissue and peripheral blood mononuclear cells. CtDNA positivity was defined as the presence of more than two tumor-derived mutations in plasma. Results: Of 145 patients analyzed (68 TNBC, 77 HER2-positive, median age 49 years), stages included stage I (2.1%), stage II (64.1%), and stage III (33.8%). The median number of mutations identified through WES was 59 (range 9-234), higher in TNBC (71 vs. 50, P = 0.002) but not by stage (P = 0.668). Baseline ctDNA positivity (P0) was 86.9% (median 20 mutations; range 0-97), significantly higher in TNBC (100% vs. 75.3%, P < 0.001) and stage III (95.9% vs. 82.3%, P = 0.021).After NAC, ctDNA clearance occurred in 86.5% of P1-positive patients, with overall ctDNA positivity at P1 dropping to 11.7%, slightly higher in TNBC (14.7% vs. 9.1%, P = 0.314). Pathologic complete response (pCR) rates post-NAC were 55.6%, similar across subtypes and stages. P1 positivity tended to be higher in non-pCR patients (15.6% vs. 7.5%, P = 0.202). CtDNA clearance was associated with higher pCR (60.6%) compared to persistent positive (37.5%, P = 0.106) or persistent negative (42.1%, P = 0.207). For TNBC, P1 positivity was associated with non-pCR (22.6% vs. 5.6%, P = 0.070), unlike HER2-positive BC (9.1% for both).At P2, 90.4% were ctDNA-negative, with positivity in 8.2% (6/73; 4 persistent positives, 2 conversions). At 23 months’ median follow-up, 5 patients developed distant metastases. Persistent positivity at P0-P1 (23.5% vs. 0.8%, P < 0.001) or P1-P2 (75.0% vs. 0%, P < 0.001) was linked to higher recurrence rates. Conclusion: The personalized ctDNA assay detected BC effectively and correlated with subtypes and stages. Post-NAC ctDNA monitoring predicted treatment response and recurrence risk. We are planning longer-term follow-up in the enrolled cohort to better validate its power in recurrence prediction. Citation Format: Yongjun Cha, Junghoon Shin, Jongseong Ahn, Sunghoon Heo, Hwang-Phill Kim, Duhee Bang, Sang-Hyun Song, Young-Hyuck Im, Ji-Yeon Kim, Tae-You Kim. Perioperative tumor-informed ctDNA monitoring for minimal residual disease in triple-negative and HER2-positive breast cancer patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 3260.