ctDNA Surveillance Pinpoints Relapse Risk in High-Risk ER+/HER2- Breast Cancer—Early Clearance Triples on Palbo + Fulvestrant

In the multicenter DARE trial (NCT04567420), 552 high-risk ER+/HER2- patients on adjuvant endocrine therapy underwent Signatera™ ctDNA testing every 6 mo. Over a median 27 mo, 432 remained ctDNA-negative and showed a 99% recurrence-free survival (RFS) at 12 mo, giving the assay a 99% negative-predictive value. Forty ctDNA-positive patients were randomised: switching to fulvestrant + palbociclib cleared ctDNA in 63% (10/16) versus 22% (4/18) on standard therapy, and rising ctDNA at 3 mo portended a five-fold higher relapse risk (HR 5.3; median time-to-recurrence 4.8 mo).