Abstract 6695: Utility of circulating tumor DNA in breast cancer clinical research and practice: systematic review and meta-analysis
Authors: Sun Xuezheng , Ballew Nicholas , Kalilani Linda , Phiri Kelesitse , Bell Kelly , Slowly Alexander , Zajac Magdalena , Hofstatter Erin , Silvestro Angela , Wang Zebin , Schilder Jeanne 
Published: April 2023

Background: Circulating tumor DNA (ctDNA) has been increasingly used in the clinical care of patients with cancer. This systematic review summarizes current data on the utility of ctDNA in breast cancer clinical research and practice and provides insights for integrating ctDNA into drug development and patient treatment.

Methods: The Embase database was used to identify original clinical research articles of ctDNA in breast cancer published from 2015 to 2020. ctDNA clinical utilities were reviewed and summarized, focusing on 3 areas: early diagnosis, prognostication, and monitoring disease progression/treatment response. Associations of ctDNA with disease-free survival (DFS) and overall survival (OS) were estimated in the embedded meta-analysis. Pooled estimates were calculated using fixed-effect or random-effect models depending on study heterogeneity.

Results: After screening and review, 72 articles were included. ctDNA studies have increased in recent years, with 59.7% of included articles published in 2019 or 2020. Overall, 61.1% of the studies were in patients with advanced stage/metastatic cancer; 45.8% were restricted to patients with specific cancer subtypes. ctDNA was minimally used in diagnosis; it was predominantly used in clinical outcome prediction with differences by stage. In patients with early-stage disease, the meta-analyses found that overall ctDNA detection/positivity was associated with shorter DFS (n=697; HR, 5.37; 95% CI, 2.94-9.80) and OS (n=238; HR, 4.60; 95% CI, 2.56-8.26). Specific gene mutations in ctDNA were mainly assessed in patients with advanced/metastatic disease, with mutations of ERBB, ESR1, and TP53 linked to shorter DFS in the meta-analyses (P&lt;0.05). Moreover, current studies provided evidence that ctDNA reflects the dynamics of breast tumors in the patient treatment journey, acting as a biomarker to monitor tumor evolution and drug resistance.

Conclusions: Recent studies demonstrate ctDNA application in breast cancer prognostication/monitoring, suggesting an important role in patient stratification, molecular relapse identification, and personalized treatment. Large, multicenter clinical trials and real-world longitudinal data sets are needed to validate findings and to address challenges related to ctDNA to improve clinical utility and to integrate ctDNA testing into clinical practice and drug development.

Citation Format: Xuezheng Sun, Nicholas Ballew, Linda Kalilani, Kelesitse Phiri, Kelly Bell, Alexander Slowly, Magdalena Zajac, Erin Hofstatter, Angela Silvestro, Zebin Wang, Jeanne Schilder. Utility of circulating tumor DNA in breast cancer clinical research and practice: systematic review and meta-analysis. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 6695.