Prognostic analysis of tissue-free versus tumor-informed ctDNA assays for molecular residual disease detection in early TNBC

Information on molecular residual disease (MRD) status could be important for selection of adjuvant therapy. Tissue-free assays not requiring sequencing of the primary tumormay simplify workflow if they offer accuracy similar to that of tumor-informed assays. A multicenter analysis of patients with early triple-negative breast cancer (TNBC) at high risk of recurrence evaluated tissue-free ctDNA analysis and compared tissue-free with tumor-informed assay results. Plasma samples were collected every 3 months for up to 2 years after the completion of adjuvant therapy. The analysis included 1026 plasma samples from 159 patients. The tissue-free assay detected ctDNA in 54 patients (34.0%), with detection strongly associated with risk of recurrence (HR 27.2; p<0.001). Among patients with ctDNA detected by both the tissue-free assay and digital polymerase chain reaction (dPCR; n=42), tissue-free detection occurred at an earlier time point in 14 patients (33.3%); in none of the patients dPCR detection occurred before tissue-free detection. Median lead time to recurrence was 7.9 months for tissue-free versus 5.8 months for dPCR (HR 0.57; p=0.03). Concordance between tissue-free and multivariant tumor-informed assays was good. Among patients detected by both assays, 29.3% had ctDNA detected earlier by multivariant tumor-informed assay with 2.4% earlier by the tissue-free assay. Median lead times to recurrence were 7.6 months with tissue-free and 7.1 months with tumor-informed assay (p=0.15). The authors conclude that in this prognostic study, tissue-free ctDNA detection was prognostic for recurrence in patients with TNBC.