Exploratory analysis of prognostic value of ctDNA monitoring among advanced breast cancer with oligometastatic disease: An ancillary biomarker study of JCOG 2110 (JCOG2110A1).

TPS1158 Background: Oligometastatic advanced breast cancer represents a biologically heterogeneous disease state in which a subset of patients may achieve prolonged disease control or potential cure through the addition of definitive local therapy to systemic treatment. However, conventional imaging has limited sensitivity for detecting minimal residual disease (MRD), and reliable biomarkers to identify patients most likely to benefit from local therapy remain lacking. Circulating tumor DNA (ctDNA) has emerged as a sensitive, minimally invasive marker of tumor burden and treatment response and may provide complementary information beyond radiographic assessment. JCOG2110 is a phase III randomized trial evaluating whether the addition of definitive local therapy (surgery or radiotherapy to all detectable lesions) to systemic therapy improves survival in patients with advanced breast cancer with three or fewer oligometastatic lesions. JCOG2110A1 is an ancillary biomarker study designed to characterize ctDNA dynamics in this clinical setting and to explore the clinical significance of ctDNA-based MRD assessment. Methods: Eligible patients are those enrolled in JCOG2110 who provide written informed consent prior to initiation of protocol-defined systemic therapy. Plasma ctDNA will be analyzed using Guardant Reveal, a next-generation sequencing–based assay integrating genomic alterations and methylation signatures, and reported as ctDNA positive or negative with quantitative estimates of tumor fraction. Blood samples will be collected longitudinally at predefined timepoints: before systemic therapy, prior to completion of the initial 12-week systemic treatment, and during protocol-specified follow-up aligned with imaging assessments after second registration. In cases of disease progression, ctDNA will be collected at progression and subsequent sampling will be discontinued. The primary endpoint is the proportion of ctDNA clearance and ctDNA level reduction after initial systemic therapy among patients who are ctDNA-positive at baseline. Secondary endpoints include ctDNA positivity at each timepoint, associations between ctDNA kinetics and radiographic tumor prognosis, and correlations with clinical characteristics such as tumor subtype, number of metastatic lesions, and treatment allocation. This study aims to define the detectability and early kinetics of ctDNA in oligometastatic advanced breast cancer and to generate prospective evidence regarding the prognostic and potential predictive value of ctDNA for treatment outcomes and benefit from local therapy. Clinical trial information: jRCTs031230439.