Abstract PO4-01-04: Clinical significance of Circulating tumor DNA (ctDNA) analysis in predicting pathologic complete remission in HER2-positive Breast Cancer Patients Undergoing Neoadjuvant Chemotherapy

Abstract Background: Neoadjuvant chemotherapy (NACT) combined with dual anti-HER2 agents followed by surgical resection is the standard treatment for stage II-III HER2-positive breast cancer. Despite the availability of effective therapies as an adjuvant treatment such as ado-trastuzumab emtansine (T-DM1) and neratinib, pathologic complete remission (pCR) strongly predicts survival. This study aimed to investigate the role of ctDNA analysis in predicting pCR and clinical outcome using comprehensive ctDNA analysis. Methods: A total of 34 HER2-positive breast cancer patients who underwent NACT combined with dual anti-HER2 agents and surgical resection were enrolled, including 22 clinical stage II and 12 III patients. Plasma samples were collected at four-time points: before neoadjuvant chemotherapy, after 3 cycles, at the completion of neoadjuvant chemotherapy, and after surgery. low-pass whole-genome sequencing (lpWGS) and whole exome sequencing (WES) in evaluating blood copy-number burden (bCNB), genomic alterations, mutational signatures, blood tumor mutational burden (bTMB). Mutations selected from the baseline sample were monitored for Molecular residual disease (MRD) monitoring. lpWGS yielded negative results, targeted NGS sequencing was conducted. Results: Among the enrolled patients (N=34), 21 patients (61.8%) had nodal metastasis and 22 patients (64.7%) were hormone receptor-positive. A total 26 patients (76.5%) achieved pCR. Positive ctDNA was detected in 20 patients (58.8%) at baseline. Higher nodal stage was significantly associated with ctDNA positivity at baseline. After surgery, MRD positivity was observed in 3 patients (8.8%). Among the 26 patents who acheived pCR, only 1 patient (3.8%) showed MRD positivity, while 2 non-pCR patients (25%) demonstrated MRD positivity. Conclusion: The presence of MRD was significantly associated with non-pCR status. The presence of ctDNA at baseline was associated with a higher nodal stage, suggesting its potential as a prognostic marker. Further studies with larger cohorts are warranted to validate these findings and explore the utility of ctDNA analysis for personalized treatment decisions in HER2-positive breast cancer. Citation Format: Byeongju Kang, Soo Jung Lee, Jeeyeon Lee, In Hee Lee, Jee-Young Park, Ho Yong Park, Tiantian Zheng, Lu Tan, Liam Il-Young Chung, Shidong Jia, Pan Du, Young Kwang Chae, Yee Soo Chae. Clinical significance of Circulating tumor DNA (ctDNA) analysis in predicting pathologic complete remission in HER2-positive Breast Cancer Patients Undergoing Neoadjuvant Chemotherapy [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-01-04.