Abstract B014: Prospective analysis of circulating tumor cell dynamics during preoperative radiotherapy in locally advanced breast cancer

Abstract Introduction: This is a per-protocol interim analysis of circulating tumor cell (CTC) dynamics among patients diagnosed with locally advanced breast cancer receiving preoperative radiotherapy (RT) on the TOPAz trial (“Trial of Preoperative Radiation”) with concurrent enrollment on a prospective observational cohort study (2022-0601). Methods: Eligible patients with clinical or pathologic T3-4 or node-positive non-metastatic breast cancer were prospectively enrolled. All patients received preoperative RT followed by mastectomy and were randomized to conventional fractionation (CFx, 50Gy/25Fx) versus hypofractionation (HFx, 40Gy/15Fx). CTCs were enumerated using the CellSearch® assay immediately prior to RT (Pre-RT) and within 1 week of completing RT (End of RT). Rates of CTC detection and clearance with RT were calculated. Results: As of August 2024, 46 enrolled patients had a Pre-RT assessment for CTCs, of which 45 (98%) received neoadjuvant chemotherapy (NAC), 30 (65%) had clinical T3-4 disease, 10 (22%) had advanced nodal (cN3) disease, 39 (85%) had estrogen receptor (ER)- positive disease, 3 (7%) overexpressed Her2, and 6 (13%) had triple negative disease. Prior to RT, 15 (33%) patients had ≥1 detectable CTC (median [IQR] = 2 cells [1-2.5]). Of the 14 CTC- positive patients with a completed “End of RT” blood draw to date, 11 (79%) achieved CTC clearance, while 3 patients had persistent CTCs (median [IQR] = 2 cells [1.5-2.5]). Patients who achieved CTC clearance had significantly lower median initial CTC count compared to patients who had persistent CTCs ((2 [1-2]) versus 8 [5-19], Kruskal-Wallis test, p<0.05). CTC status at either time point was not significantly associated with clinicopathologic or treatment variables. Of the 9 CTC-positive patients who achieved CTC clearance and completed surgery, 1 experienced pCR (11%) while all 3 patients with persistent CTCs had residual disease. The median RCB index score for patients without detectable CTCs at End of RT (n=33) was 2.9 [1.4- 3.4] versus 3.3 [2.2-3.4] for the 3 patients with persistent CTCs. In a subgroup of 37 patients with ER+ Her2- disease, 11 (30%) patients had detectable CTCs prior to RT. Of the 10 with completed “End of RT” blood draw to date, 8 (80%) achieved CTC-clearance. The median RCB index score for patients without detectable CTCs at End of RT (n=27) was 3.0 [1.5-3.6] versus 3.4 [3.4-3.4] for the 2 patients with persistent CTCs. Conclusion: In this prospective analysis of CTC dynamics during preoperative RT for patients with locally advanced breast cancer, one- third of patients had detectable CTCs prior to RT (33%). Following comprehensive RT, 79% of patients with detectable CTCs prior to RT experienced CTC clearance prior to surgical resection. All patients with persistent CTCs had residual disease at surgery. These interim results support further study of longitudinal monitoring of circulating tumor material as a potential real-time biomarker for residual locoregional disease in the preoperative setting. Citation Format: Chelain R Goodman, Simona F Shaitelman, Saleh Ramezani, Jonathan B. Strauss, Anam Zia, Nathan Comeaux, Ritupreet Virk, Ruitao Lin, Kevin Nead, Melissa P Mitchell, Karen E Hoffman, Eric Strom, Michael Stauder, George Perkins, Valerie Reed, Elizabeth Bloom, Melissa Joyner, Pamela Schlembach, Vicente Valero, Bora Lim, Carlos H Barcenas, Anthony Lucci, Wendy A Woodward, Benjamin D Smith. Prospective analysis of circulating tumor cell dynamics during preoperative radiotherapy in locally advanced breast cancer [abstract]. In: Proceedings of the AACR Special Conference: Liquid Biopsy: From Discovery to Clinical Implementation; 2024 Nov 13-16; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(21_Suppl):Abstract nr B014.