Abstract
BACKGROUND: Neoadjuvant endocrine therapy (NET) is used in hormone receptor (HR)-positive, HER2-negative breast cancer to reduce tumor burden before surgery. However, robust biomarkers to predict benefit from NET are lacking. PATIENTS AND METHODS: We evaluated the potential of circulating tumor DNA (ctDNA) before treatment and the dynamics during NET to guide treatment decisions for patients receiving NET. In this retrospective analysis, ctDNA before and after NET from patients enrolled in the phase II PELOPS trial, was assessed using the tissue-free Guardant Reveal assay. RESULTS: ctDNA was detected at the pre-NET timepoint in 37.5% of patients (18/48) and 13.6% (6/44) of patients following NET. Pre-NET ctDNA detection was associated with higher pathological stage and higher residual cancer burden scores after NET. Patients with persistent ctDNA detected pre-surgery had a higher risk of distant recurrence. CONCLUSIONS: Taken together, these results support the potential of ctDNA to predict tumor burden before surgery after NET and provide insights into long-term prognosis. CLINICAL TRIAL NUMBER: ClinicalTrials.gov NCT02764541.