Abstract PS4-02-25: Single Institution experience of longitudinal post-surgical circulating tumor DNA monitoring in patients with HER2+ breast cancer

Abstract Background: Recent studies have demonstrated the utility of longitudinal circulating tumor DNA (ctDNA) testing for monitoring treatment response and predicting long-term outcomes in patients (pts) with breast cancer (BC). In this study, we evaluated ctDNA detection rates post-surgery in pts with HER2+ BC in the adjuvant treatment and surveillance settings. Methods: This retrospective study included 59 patients with stage I-IV HER2+ BC. Commercial CTDNA testing was performed postoperatively at the physician's discretion. A clinically validated, tumor-informed ctDNA assay (SignateraTM, Natera, Inc.) was used to detect and quantify ctDNA in blood samples collected after primary resection and serially during surveillance. ctDNA status and dynamics were correlated with clinicopathological features and surgical outcomes. Results: The cohort included 59 patients with HER2+ BC; the majority of pts had clinical T1-3 stage disease at diagnosis (T1, 25%, 15/59; T2, 20%, 12/59; and T3, 24%, 14/59), the remaining pts were T4 (7%; 4/59) or had unknown stage (24%; 14/59). Lymph node involvement was reported in 46% of pts (27/59; stage N1, 22/59; N2, 3/59; N3, 2/59); 47% had grade 3 (28/59) and 46% had grade 2 (27/59) disease. Sixty-four percent of cases (38/59) were estrogen receptor (ER)-positive; 36% (21/59) were ER-negative. Neoadjuvant treatment was received by 71% (42/59) of pts, this information was unavailable for 4% (2/59); the rest of the pts (25%; 15/59) did not receive neoadjuvant treatment. Among pts receiving neoadjuvant therapy (n=42), residual cancer burden (RCB) class was available for 27 (RCB0: 22%, 6/27; RCB1: 19%, 5/27; RCB2: 40%, 11/27; RCB3: 19%, 5/27). Among pts with longitudinal ctDNA results and complete clinical information available (n=42), ctDNA-positivity any time after surgery was observed in 14% (6/42) with a median time to ctDNA-positivity of 34 months (range: 14-792) from surgery. Of these six ctDNA-positive patients, one experienced recurrence 13 months after the first positive ctDNA test, one experienced ctDNA clearance after adjuvant therapy and remained event-free for 4.6 mos, and four remained recurrence-free with a median follow-up since ctDNA-positivity of 6.7 months and ongoing monitoring. Among patients with a favorable response to neoadjuvant treatment (RCB 0/1; n=11), no ctDNA-positivity was observed after surgery. Among pts with residual disease at surgery (RCB 2/3; n=10), ctDNA-positivity was observed in 20% (2/10). Among pts with persistent ctDNA-negativity during surveillance (n=30, median follow-up of 15.4 months, range: 5.9-50.0 months), no clinical recurrences were reported. Conclusions: In addition to clinicopathological features and surgical outcomes, longitudinal ctDNA monitoring helps identify pts with HER2+ BC who may be at high risk of recurrence. Further research is needed to assess the true utility of a ctDNA-guided treatment approach in this patient population. Citation Format: Y. Gao, M. Zaidi, A. Naqvi, F. Azim, S. Satta, C. Brewer, C. Palsuledesai, E. Kalashnikova, K. Sun, P. Niravath, H. Mai, J. McKenzie, A. Rodriguez, M. Liu, A. Puri. Single Institution experience of longitudinal post-surgical circulating tumor DNA monitoring in patients with HER2+ 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 PS4-02-25.