Abstract P2-03-30: Association of ctDNA in patients with long-term outcome of breast cancer patients undergoing neoadjuvant treatment in the randomized ABCSG 34 clinical trial

Abstract Introduction: Circulating tumor DNA (ctDNA) represents a minimally invasive assessment of tumor response based on longitudinal ctDNA analyses. In the neoadjuvant prospective ABCSG 34 trial, we have previously shown that lacking ctDNA clearance correlated with poor response to neoadjuvant systemic treatment (NST) assessed as pathological response (pCR) and residual cancer burden (RCB). In a follow-up analysis, we investigate the impact of ctDNA detection and clearance (or lack thereof) on long-term outcome invasive disease free survival (iDFS), distant recurrence free survival (DRFS), and overall survival (OS). Experimental design: Previously, tumor-informed assays based on analyses of 93 genes in tissue were designed for 145 patients with sufficient plasma cell free DNA, and ctDNA presence/absence/clearance in plasma was evaluated before (BL, baseline) , during (MT, mid-therapy), and at the end of neoadjuvant treatment (EOT). In the present analyses, follow up data on invasive disease free survival (IDFS), distant recurrence free survival (DRFS) and overall survival (OS) were available from 109 patients. Association of [DH1] BL, MT and EOT ctDNA status with outcomes was analyzed. Median FU starting from surgery was 7.1 years. Results: Twenty of 49 patients (40.8%) with detectable ctDNA at BL had an IDFS event, while out of 60 patients who were ctDNA negative at baseline, 19 (31.7%) experienced an IDFS event (HR 1.53 (0.81 - 2.86, p=0.187). IDFS rate at 7 years was 58.5% vs. 70.8%. DRFS rate was 60.9% in patients with detectable baseline ctDNA vs. 77.9% in ctDNA negative patients (HR 1.98, 95% CI 0.99 - 3.95, p=0.053). OS rate at 7 years was 62.7% for ctDNA+ compared with 81.2% in ctDNA- patients (HR 2.12, 95% CI 1.02 - 4.41, p=0.043), respectively. In contrast to BL there was no significant association of ctDNA status with IDFS, DRFS and OS at MT or EOT, even though the HR are comparable, due to smaller numbers significance could not be reached. [DH2] [DE3] Conclusions: Overall, our results demonstrate that in our cohort the detection of ctDNA at BL was associated with IDFS, DRFS and OS. [DH4] [DE5] Limited numbers of available MT and EOT samples reduced the power of analyses of ctDNA dynamic changes under treatment and their association with long term outcome, therefore results didn’t reach significance. In summary, BL ctDNA assessment is useful to assess long-term prognosis in patients receiving neoadjuvant NST. Citation Format: Daniel Egle, Dominik Hlauschek, Simon Gampenrieder, Gabriel Rinnerthaler, Christian Singer, Georg Pfeiler, Rupert Bartsch, Gregor Huber, Angelika Pichler, Edgar Petru, ZsuZsanna Bago-Horvath, Anna Kermanidis, Christian Fesl, Ricarda Graf, Sabrina Weber, Nadia Dandachi, Martin Filipits, Michael Gnant, Ellen Heitzer, Marija Balic. Association of ctDNA in patients with long-term outcome of breast cancer patients undergoing neoadjuvant treatment in the randomized ABCSG 34 clinical trial [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2024; 2024 Dec 10-13; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(12 Suppl):Abstract nr P2-03-30.