Abstract
BACKGROUND: Current aftercare in breast cancer survivors aims to detect local recurrences or contralateral disease, while the detection of distant metastases has not been a central focus due to a lack of evidence supporting an effect on overall survival. However, the data underpinning these guidelines are mainly from trials of the 1980s/1990s and have not been updated to reflect the significant advancements in diagnostic and therapeutic options that have emerged over the past 40 years. In this trial, the aim is to test whether a liquid biopsy-based detection of (oligo-) metastatic disease at an early pre-symptomatic stage followed by timely treatment can impact overall survival compared to current standard aftercare. METHODS: In this partially double-blinded superiority study, intensified liquid biopsy-guided surveillance will be assessed versus standard surveillance in medium-to-high-risk early breast cancer patients. Intensive surveillance comprises 3-monthly tests of circulating free tumor DNA (ctDNA), circulating tumor cells (CTC) and serum tumor markers CEA, CA 27.29 and CA125. Upon positivity of biomarker and/or symptoms, staging examinations are initiated. In total, 3500 patients will be randomized in a 1:1 ratio after completion of primary antineoplastic therapy. Co-primary endpoints are overall survival (OS) and the overall lead time effect. The trial will be accompanied by an extensive translational research program. DISCUSSION: A risk-based aftercare and regular screening for asymptomatic metastatic disease with molecular markers in the absence of any radiological findings can potentially revolutionize current follow-up care of breast cancer survivors and enable potential treatment even before patients suffer from symptomatic, incurable disease.