Abstract 720: Analysis of circulating tumor DNA after neoadjuvant therapy to predict disease relapse in patients with stage II-III breast cancer

Abstract

Abstract The therapeutic efficacy of neoadjuvant chemotherapy for patients with breast cancer is usually assessed by the reduction of tumor size and lymph nodes. The pathologic complete response (pCR) is considered as a marker related to good prognosis. However, patients who can achieve pCR is a minor population, and pCR may be not a robust marker predicting prognosis in patients with ER-positive breast cancer. Additional markers allowing the assessment of prognosis is needed. Circulating tumor DNA (ctDNA) has been proved as a marker to detect disease progression in metastatic breast cancer and predict relapse in patients after resection of breast cancer. Therefore, we would like to assess the value of ctDNA in breast cancer patients receiving neoadjuvant therapy. The ctDNA was collected before and after completion of the neoadjuvant chemotherapy (Tend). The presence of ctDNA was detected by ultra-deep targeted next-generation sequencing. We enrolled 82 patients and 62 patients were found to have ctDNA as the biomarkers. The presence of ctDNA included nonsynonymous variants and copy number variations in TP53, PIK3CA, HER2, CDH1, PTEN, S100A, CCND1 and c-MYC. Among the 62 patients, there were 24 patients with hormone receptor (+)/Her2(-), 20 with Her2(+) and 18 with triple-negative breast cancer (TNBC). Pathologic complete response (pCR) occurred in 9 patients, partial response in 32 patients and stable/progression in 21 patients, according to the RECIST 1.1 criteria. Univariate analysis showed tumor reduction>50% (p=0.032), number of metastatic lymph node (p=0.039), and status of ctDNA at Tend (p<0.001) were significantly associated with disease-free survival (DFS). The 5-year DFS of patients with undetectable ctDNA at Tend (74.0%, 95% confidence interval (CI) range 98%-50%) was significantly superior to those with detected ctDNA (16.8%, 95% CI range 36.1%-0%). Multivariate analysis revealed that status of ctDNA at Tend was the only one independent factor predicting relapse (hazard ratio 7.74, 95% CI 2.81-21.35). Two patients had pCR and were found to have alterations of ctDNA at Tend; one with TNBC had distant metastases at 6 months after mastectomy and the other with Her2 (+) breast cancer had brain metastasis at the end of adjuvant trastuzumab treatment. Therefore, we concluded that the presence of ctDNA at the end of the neoadjuvant chemotherapy was a poor prognostic factor predicting relapse in patients with stage II-III breast cancer. Citation Format: Po-Han Lin, Sung-Sheng Kuo, Chiun-Sheng Huang. Analysis of circulating tumor DNA after neoadjuvant therapy to predict disease relapse in patients with stage II-III breast cancer [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 720.