26P ctDNA prognostic and diagnostic value for recurrence in patients with early-stage breast cancer: A systematic review and meta-analysis

Circulating tumor DNA (ctDNA) assessment in blood is being studied as a biomarker in breast cancer. We aimed to assess the clinical value of ctDNA in patients with early breast cancer. Systematic search of databases (PubMed, Embase, CENTRAL) up to 23/Nov/22 and conferences proceedings (ASCO, ESMO, AACR, SABCS, ESMO Breast) 2020-2022 was conducted to identify studies reporting the association of ctDNA detection with disease-free survival (DFS), and overall survival (OS) in patients with stage I-III breast cancer (PROSPERO ID: CRD42021286591). ctDNA assays were classified as tumor-informed and non-tumor informed. Timepoints of ctDNA collection were grouped as baseline (BL), after neoadjuvant therapy (End-of-NAT), and during follow-up period (FUP). Univariable (Uv) and multivariable (Mv) hazard ratios (HR) were pooled using random-effects models and reported with their 95% confidence intervals (CI). Of 3,174 identified records, 57 studies were included in this analysis reporting data from 5,729 patients with early breast cancer. 44.5% had breast cancer stage reported (18.3%, 60.0%, and 21.5% had stages I, II, and III, respectively). We found a statistically significant association of ctDNA detection at any timepoint with worse DFS and OS (Table). Pooled HRs were numerically higher when ctDNA was detected at end-of-NAT or FUP than at BL, and for tumor-informed compared to non tumor-informed assays. ctDNA detection sensitivity and specificity for breast cancer relapse ranged from 0.31-1.0 and 0.7-1.0, respectively. The mean lead time to radiological recurrence was 10.81 months (0-58.9).Table: 26PTimepointHR (95%CI)Tumor-informedNon tumor-informedOverallDFSBLUv4.2 (1.8-9.8)2.8 (1.7-4.6)3.0 (1.9-4.6)Mv1.9 (1.1-3.2)2.7 (2.0-3.8)2.5 (1.9-3.3)End-of-NATUv8.9 (5.1-15.4)4.4 (2.6-7.2)7.7 (4.8-12.2)Mv9.9 (2.7-35.5)2.7 (1.3-5.8)5.5 (2.4-12.8)FUPUv16.0 (8.4-30.6)14.0 (7.5-26.1)Mv12.2 (2.8-53.3)2.6 (1.1-6.3)7.2 (2.8-6.3)OSBLUv2.6 (1.5-4.7)2.8 (1.6-4.8)Mv3.0 (1.4-6.4)End-of-NATUv2.6 (1.0-6.4)2.7 (1.4-5.1)Mv12.9 (0.4-380.2)FUPUv22.7 (9.3-55.7)4.0 (2.3-7.0)9.2 (3.3-25.9)Mv6.7 (0.2-224.4)6.2 (3.1-12.4)5.6 (1.5-21.8) Open table in a new tab ctDNA detection is associated with worse DFS and OS in patients with early breast cancer, particularly when measured after treatment with tumor-informed assays. ctDNA detection has a high specificity for the diagnosis of breast cancer relapse.