Abstract PD5-07: Prospective Analysis of Circulating Tumor Cell Clearance and Dynamics with Adjuvant Radiotherapy in Locally Advanced Breast Cancer

Abstract Background: Detection of circulating tumor cells (CTCs) is a strong prognostic biomarker for clinical outcomes in non-metastatic breast cancer. The kinetics of CTC clearance with adjuvant radiotherapy (RT) and its utility as a predictive biomarker have not been well characterized. Here we present the results of a prospective observational cohort study evaluating the dynamics of CTC detection and response to adjuvant breast radiotherapy. Methods: Patients with clinical or pathologic T3-4 or node-positive non-metastatic breast cancer dispositioned to receive comprehensive regional nodal irradiation (RNI) were prospectively enrolled. CTCs were enumerated using the CellSearch® assay immediately prior to RT (Pre-RT), within 1 week of RT (End of RT), and at follow-up 3-6 months following RT (Post-RT). Rates of CTC detection at each time point and clearance with RT were estimated. Associations between CTC status with clinicopathologic and treatment variables were performed using McNemar’s Exact, Wilcoxon, Fisher’s Exact, or Mann Whitney U Tests, as appropriate. For all applicable analyses, statistical significance was defined as a P-value of <0.05 (two-tailed). Results: At 28 months post study activation, 249 patients completed Pre-RT assessment of CTCs. The majority of patients were hormone receptor positive (HR+Her2-, 66%; Her2+, 13%; TNBC: 21%) and were treated with (neoadjuvant, 61%; adjuvant, 17%; none, 23%), mastectomy (69%) and axillary lymph node dissection (61%). Prior to RT, 61 (25%) of patients had ≥1 detectable CTC (median=1 cell [IQR, 1-2]). Of the CTC-positive patients who completed subsequent blood draws, 69% (n=42 of 61) achieved CTC clearance by the End of RT (McNemar’s Exact, P<0.001), with a further increase to 90% (n=55 of 61) by first Post-RT follow-up (P=0.002). Of the CTC-positive patients, 22% (n=13 of 59), 17% (n=9 of 53) and 20% (n=16 of 79) demonstrated Her2+ CTCs at each timepoint, respectively (Cochran’s Q Test, P=0.69). Detection of Her2-expressing CTCs was more common in patients with Her2+ primary tumors (25% versus 12%, P=0.05). Pre-treatment CTC-positive status was significantly associated with advanced nodal disease (cN3, 23% vs 11% p=0.04) but not subtype, grade, or lymphovascular space invasion. Of the 47 patients who achieved pCR with surgery, 30% (n=14) had detectable CTCs prior to RT. Clearance of CTCs was not significantly associated with any tested clinicopathological or treatment-related variable, including pathologic complete response (pCR) and residual cancer burden score. Conclusion: In this large prospective analysis of patients with locally advanced breast cancer, 25% of patients had detectable CTCs prior to radiotherapy; 30% of patients with pCR had detectable CTCs. Following comprehensive RT, 90% of CTC-positive patients achieved clearance of CTCs by first follow-up. While delayed CTC clearance without RT cannot be assessed on this single arm study, these results support further study of longitudinal monitoring of circulating tumor material as a potential real-time biomarker for residual locoregional disease prior to RT as well as a potential surrogate for radiotherapeutic efficacy. Citation Format: C. R. Goodman, S. F. Shaitelman, S. Ramezani, K. Hoffman, M. P. Mitchell, N. Comeaux, A. Zia, C. Barcenas, B. Lim, B. D. Smith, A. Lucci, W. A. Woodward. Prospective Analysis of Circulating Tumor Cell Clearance and Dynamics with Adjuvant Radiotherapy in Locally Advanced 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 PD5-07.