Mature five-year outcomes of serial circulating tumour DNA testing in Taiwanese early breast cancer treated with upfront surgery: results from the VGH-TAYLOR study

<title>Abstract</title> <p> Circulating tumour DNA (ctDNA) is a candidate biomarker of molecular residual disease in early breast cancer, but most reports rest on short follow-up. We analyzed 577 stage I-III patients treated with upfront surgery in the VGH-TAYLOR study who had at least one liquid biopsy with the Oncomine Breast cfDNA Assay v2 with a median follow-up of 60.6 months. Among 560 evaluable patients, 48 recurrence-free survival (RFS) events occurred (37 recurrences, 21 deaths). ctDNA was detected pre-operatively in 117 of 500 patients (23.4%), most often <italic>TP53</italic> (20.4%) and <italic>PIK3CA</italic> (5.6%), and persisted or reappeared during follow-up in 13 of 211 patients with paired samples (6.2%), always in a baseline-positive, <italic>TP53</italic> -mutated context. Five-year RFS was 92.7% (95% CI 87.7-95.7) for ctDNA-negative/negative, 82.4% (54.7-93.9) for positive/negative and 76.2% (42.7-91.7) for positive/positive patients (trend P = 0.048; positive/positive hazard ratio 3.39, 95% CI 0.97-11.91). Five-year distant RFS differed significantly (95.5%, 94.1% and 75.5%; P = 0.024). With mature follow-up, persistent ctDNA marks a roughly three-fold higher risk of distant relapse, whereas pre-operative detection adds little prognostic information. Trial registration: ClinicalTrials.gov NCT04626440 (VGH-TAYLOR). </p>