Abstract CT171: Early findings from MONITOR-Breast: ctDNA dynamics during neoadjuvant therapy using an ultrasensitive MRD assay

Abstract Introduction: In patients with breast cancer receiving neoadjuvant therapy, treatment decisions are primarily guided by predefined imaging and clinical assessments. Circulating tumor DNA (ctDNA)-based molecular residual disease (MRD) testing offers a real-time measure of response to help guide escalation and de-escalation strategies. Prior studies have evaluated binary MRD status at limited timepoints, providing low resolution and minimal quantitative insight. The MONITOR-Breast study uses an ultrasensitive whole-genome sequencing (WGS)-based assay with frequent ctDNA sampling across the neoadjuvant period. Here, we report results from this multi-center prospective study evaluating the association between post-treatment ctDNA status and pathologic complete response (pCR), providing quantitative, high-resolution data on ctDNA dynamics. Methods: Patients with stage I-III breast cancer planning to receive neoadjuvant chemotherapy were prospectively enrolled. WGS of core needle biopsy tissue was used to design personalized panels with up to 1,000 variants (Precise MRD, Myriad Genetics). Plasma was collected pre-treatment, at each cycle, after therapy, at surgery, and at post-op follow-up. ctDNA trajectories were evaluated by subtype and treatment relative to pCR or residual disease (RD). At the time of analysis, tumor and normal samples from 108 patients completed WGS and panel building; personalized panels were created for 99 (91.6%), and 91 had baseline plasma available. Results: MRD results were analyzed for 91 patients and 910 plasma samples (median=10). Subtypes were HR+/HER2- (n=24), HR+/HER2+ (n=22), HR-/HER2+ (n=9), and TNBC (n=36). Stages were I (n=24), II (n=49), and III (n=18). Treatments included chemotherapy (n=91), HER2-targeted therapy (n=31), and immunotherapy (n=38). Median follow-up was 17 months, and 84 cases had pathologic response data available. Baseline ctDNA was detected in 84/91 (92.3%) patients: 66 (78.6%) >100 parts per million (PPM), 12 (14.3%) 20-100 PPM, and 6 (7.1%) <20 PPM. ctDNA declined rapidly during therapy; by 50 days, 58% were ctDNA-, increasing to 85% by surgery. HER2+ and TNBC tumors showed faster clearance than HR+ disease. ctDNA status was significantly associated with pathological response (p < 0.0001); ctDNA was negative in all patients with pCR (n=43) (100% specificity), while among those with RD (n=41), 28 were ctDNA- and 13 were ctDNA+. PPV was 100%. Conclusions: Ultrasensitive, personalized ctDNA monitoring enables high-resolution tracking of neoadjuvant response. ctDNA clearance following neoadjuvant therapy was strongly associated with pCR, supporting the clinical validity of ultrasensitive MRD for assessing neoadjuvant treatment response and the feasibility of integrating MRD into neoadjuvant management. Citation Format: Julia Foldi, Greg Hogan, Matt LaBella, Brent Mabey, Marija Balic, Dale Muzzey, Katie Johansen Taber, Jeff S. Jasper. Early findings from MONITOR-Breast: ctDNA dynamics during neoadjuvant therapy using an ultrasensitive MRD assay [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(8_Suppl):Abstract nr CT171.