PS5-09-25: Claire: a multicenter, prospective single-arm phase II study, evaluating liquid biopsy guided intensified follow-up surveillance in patients with intermediate to high-risk ER+/HER2-negative early-stage breast cancer

Abstract Background: Estrogen receptor-positive, HER2-negative (ER+/HER2-) breast cancer is the most common subtype, accounting for the majority of diagnoses. Despite favorable overall survival rates, it is responsible for over sixty percent of breast cancer-specific deaths. At present, no imaging or laboratory surveillance is recommended to detect metastatic recurrence in asymptomatic patients with early-stage breast cancer (EBC). Circulating tumor DNA (ctDNA), measured using fit-for-purpose, highly sensitive and specific assays anticipates clinical relapse with high positive predictive value and long lead times, creating the opportunity for targeted secondary adjuvant interventions aimed at reducing mortality in this setting. Eligibility Criteria: Circulating Liquid biomarkers for Assessment and Identification of Recurrence in Early breast cancer (CLAIRE) is a multicenter, single-arm phase II study enrolling adults (≥18 years) with resected stage I-III ER+/HER2- EBC who completed curative-intent therapy [(neo)adjuvant chemotherapy, surgery, radiotherapy] within five years, or between 5-10 years of enrolment with a high CTS5 score. Additional eligibility criteria include no clinical evidence of recurrence, completion of ≥24 months of endocrine therapy (and ≥12 months of CDK4/6 inhibitor, if indicated), and adequate organ function. Methods: Clinical follow up will be performed per the standard of care by the primary general practitioner or medical oncologist. Participants will receive ctDNA testing (Pathlight, SAGA Dx) every three months for up to five years alongside standard clinical surveillance. Patients with ctDNA positivity will undergo reflex restaging imaging to exclude metastatic disease. Participants with ctDNA identified in the absence of radiographic relapse will be eligible for accompanying secondary adjuvant interventional trials. Aims: The two primary objectives of CLAIRE are to determine, among ctDNA-positive participants, the incidence of imaging-negative molecular relapse and, among ctDNA-negative participants, the cumulative rate of local or distant recurrence as a cumulative incidence measure. Secondary objectives include the technical and patient-centered performance of the surveillance program (assay success rate, adherence to testing, patient-reported outcomes, and health-care utilization), as well as key clinical and outcomes: distant recurrence-free survival (DRFS), overall survival (OS), and longitudinal quality-of-life (QoL) assessments. Conclusion: CLAIRE will prospectively evaluate serial ctDNA surveillance using a next-generation ultrasensitive ctDNA assay in ER+/HER2- EBC, and identify patients with MRD for interventional trials. The integration of ctDNA-guided surveillance with standard follow-up has the potential to enable targeted therapeutic interventions for those at imminent risk. Ultimately, CLAIRE seeks to demonstrate that a liquid biopsy surveillance strategy, using this ultrasensitive ctDNA assay, enables molecular recurrence detection, informing confirmatory phase III secondary-adjuvant therapy trial design. Clinical Trial Information: NCT05196087 Citation Format: M. J. Elliott, E. Amir, M. Nadler, M. Li, C. Yu, M. Audoin, G. Putcha, W. Levin, S. Birkeäl, K. Howarth, P. L. Bedard, L. L. Siu, H. K. Berman, C. Townsley, M. Wu, D. W. Cescon. Claire: a multicenter, prospective single-arm phase II study, evaluating liquid biopsy guided intensified follow-up surveillance in patients with intermediate to high-risk ER+/HER2-negative early-stage breast cancer [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS5-09-25.