Abstract P4-02-07: A large real-world study of circulating tumor DNA in early breast cancer patients
Authors: Liu Qiang , Wu Mengzi , Li Shunying , Li Yudong , Jin Liang , Shi Qianfeng , Zhang Yu , Gong Chang 
Published: March 2023

Abstract
Background Around 30-40% of early breast cancer (EBC) patients relapse after curative surgery and systemic treatment. However, it is very difficult to identify the patients with high risks of relapse. Recently, circulating tumor DNA (ctDNA) is shown to be a sensitive method to evaluate the minimal residual disease (MRD) of solid tumors after surgery. Here, we explored the prognostic value of ctDNA in a large real-world study of EBC patients.
Method 346 invasive EBC patients from three hospitals in China were enrolled in this study. All patients received radical surgery and were followed up for a median of 13.1 months from surgery. 17 patients developed local and/or distant relapse during the follow-up. Primary breast cancer samples (n=346) and plasma samples (n=1059) were subjected to deep targeted sequencing using a large next-generation sequencing panel that covers 1,021 cancer-related genes.
Results Among the 346 patients, 153 patients had detectable ctDNA in at least one of the plasma samples and 15 of them relapsed. Only two of the 193 patients with consistent negative ctDNA relapsed, demonstrating the value of positive ctDNA in predicting RFS (p&lt; 0.0001; HR=13.09; 95%CI: 2.98-57.45).
Of 334 patients who had postoperative plasma samples tested, 108 patients with positive ctDNA in at least one of the postoperative plasma samples had 11 relapse during follow-up, which had a significantly worse RFS than the 226 patients with negative postoperative ctDNA and 4 relapse (p&lt; 0.0005; HR=5.98; 95%CI: 1.90-18.79).
In this study, 176 patients received neoadjuvant therapy (NAT) and 59 of them had twice or more ctDNA tests before surgery. Among them, 12 patients with negative ctDNA before NAT remained negative before surgery and had no relapse, 36 patients with positive ctDNA before NAT turned negative before surgery and had 4 relapse, while 11 patients kept positive ctDNA before surgery and had 2 relapse.
165 patients received NAT and had postoperative ctDNA tests. Of the 31 patients achieved pCR, 21 patients with negative postoperative ctDNA did not relapse and 10 patients with positive postoperative ctDNA had 1 relapse. Of the 134 non-pCR patients, 90 patients with negative postoperative ctDNA had 4 (4.4%) relapse, which is significantly better than the 44 patients with positive postoperative ctDNA and 8 (18.2%) relapse (p&lt; 0.05), indicating the feasibility to further distinguish the real high-risk patients among the patients with non-pCR after NAT.
Among the 17 patients with relapse or metastasis, 11 patients had positive ctDNA after surgery before relapse and the median lead time was 74 days and a maximum of 526 days. Four patients had negative ctDNA before relapse and two patients did not test after surgery.
Conclusions Circulating tumor DNA is a sensitive assay to predict the relapse in early breast cancer, especially in the patients who received NAT and did not achieve pCR. This may provide a window of opportunity to personalize the escalated adjuvant treatment in patients with high relapse risk.
Table 1. The association between patients’ characteristics and ctDNA positivity
Citation Format: Qiang Liu, Mengzi Wu, Shunying Li, Yudong Li, Liang Jin, Qianfeng Shi, Yu Zhang, Chang Gong. A large real-world study of circulating tumor DNA in early breast cancer patients [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P4-02-07.