Abstract PO2-15-02: Personalized circulating tumor DNA (ctDNA) monitoring can early identify disease progression and predict prognosis in patients with breast cancer undergoing neoadjuvant therapy
Authors: Liu Yunjiang , Shi Chao , Zhang Xiangmei , Ren Xiaofei , Wu Shang , Wang Yaxian , Che Yue , Xu Zanmei , Pang Fei 
Published: May 2024

Background:

Circulating tumor DNA (ctDNA) analysis offers a non-invasive method to assess tumor burden during treatment. Although some data have been reported on the use of ctDNA in neoadjuvant therapy (NAT) for breast cancer (BC), there is a lack of data on neoadjuvant efficacy and prognosis in China specifically using tumor-informed personalized ctDNA monitoring panel.

Methods:

We performed personalized ctDNA analyses at different time of NAT (before, during, and after) in 19 patients with Stage IIA-IIIB BC. WES was conducted on tumor tissues, and single nucleotide variants (SNVs) (20-40) were selected for each patient to ensure accurate and sensitive detection of individual ctDNA(Shanghai OrigiMed Co., Ltd.).

Results:

A total of 19 BC patients, 6 HER2-negative and 13 HER2-positive, were enrolled at the Breast Center, Fourth Hospital of Hebei Medical University (China) from June 2022 to May 2023. The median age of the patients was 53 (min-max: 28-64) years old. Through WES, it was discovered that 78.5% (3377/4303) of the mutated genes were unique to each patient. Additionally, 96.1% (637/663) of the selected tumor-informed SNVs were VUS variants. These findings suggest that tumor-informed ctDNA monitoring is more effective than panel-based ctDNA monitoring in BC. Among the patients, 84% (16/19) completed baseline blood collection, 63% (12/19) completed blood collection after NAT and 42% (8/12) patients completed blood collection after the surgery. The baseline positivity rate was 100%, and the baseline ctDNA variant allele frequency was significantly associated with T stage and N stage (both p &lt; 0.01). This suggests that designing a panel based on puncture samples is feasible for ctDNA analysis. The detection of ctDNA before surgery after NAT correlated with the postoperative ctDNA status. Patients with persistently negative ctDNA during NAT were associated with pathologic complete response (pCR), although the difference was not statistically significant due to the small sample size (n=7). In 84% of patients, dynamic changes in ctDNA aligned with imaging findings, indicating a correlation between ctDNA and disease progression.

A 56-year-old patient with HER2-negative stage IIIC BC had persistent ctDNA positivity during NAT. Imaging evaluation showed disease progression, with ctDNA allele frequency increasing 18 days before detection on imaging. After surgical tumor removal, the pathology assessment revealed a change in HER2 status from negative to positive. The patient received adjuvant chemotherapy combined with HER2-targeted therapy, resulting in a transition from positive to negative ctDNA status. The disease has remained stable for nearly 9 months. A 29-year-old patient with HER2-positive stage IIIA BC underwent NAT for 8 cycles. Due to drug intolerance, the treatment was interrupted multiple times during the first 4 cycles, and ctDNA remained positive. After modifying the treatment regimen in the 5th cycle, ctDNA became negative until the patient underwent surgery. The postoperative pathology evaluation revealed a pCR.

Conclusions:

Personalized ctDNA monitoring is more effective than panel-based ctDNA (a predefined set of cancer-associated genes) monitoring in BC. The status of ctDNA before and after surgery following NAT may be correlated, suggesting that patients with positive ctDNA before surgery may benefit from intensive therapy. More importantly, dynamic changes in ctDNA closely align with radiological findings, enabling early detection of disease progression and guiding treatment modifications.

Citation Format: Yunjiang Liu, Chao Shi, Xiangmei Zhang, Xiaofei Ren, Shang Wu, Yaxian Wang, Yue Che, Zanmei Xu, Fei Pang. Personalized circulating tumor DNA (ctDNA) monitoring can early identify disease progression and predict prognosis in patients with breast cancer undergoing neoadjuvant therapy [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 PO2-15-02.