Detection of Circulating Tumor DNA Using a Tissue-Free Epigenomic Assay Is a Highly Prognostic Biomarker in Early-Stage Triple-Negative Breast Cancer

Purpose: Clinical tools to monitor treatment response and surveillance time points. Plasma samples were analyzed by metastatic risk could improve early-stage triple-negative breast Guardant Reveal. cancer (TNBC) care. Although molecular residual disease assays Results: A total of 119 patients with TNBC were included in show promise, their use in the neoadjuvant setting requires the analysis. ctDNA was detected in the postsurgical setting in rapid turnaround times. Tissue-informed approaches may be 8.9% (7/79) of patients, with an 83% (5/6) patient-level surveilchallenging for patients with limited biopsy samples. The ob- lance sensitivity for metastatic recurrence and 99.5% (197/198) jectives were to determine the surveillance sensitivity for sample-level specificity. Postsurgical ctDNA detection was progdetecting metastatic recurrence and evaluate the ctDNA re- nostic for the shorter recurrence-free interval (HR, 37.7; sponse to neoadjuvant therapy (NAT) using a tissue-free epi- P < 0.0001). ctDNA detection at the post-NAT presurgical time genomic assay. point was also associated with a shorter recurrence-free interval Experimental Design: Patients with stage II or III TNBC in patients with residual disease at surgery (HR, 28.2; P < 0.0001). undergoing neoadjuvant docetaxel and carboplatin chemo- Conclusions: In patients with early-stage TNBC, a tissue-free, therapy on a clinical trial (NCT02124902) followed by surgery epigenomic assay demonstrated high specificity and sensitivity with or without adjuvant therapy were included in this study. for metastatic recurrence. ctDNA detection in the neoadjuvant Blood samples were prospectively collected before, during, and setting indicated poor prognosis, highlighting its potential role after completion of NAT and after surgery at prespecified across breast cancer care.