Abstract PS5-11: Ultrasensitive ctDNA Tracking Predicts Exceptional Response in HER2+ Metastatic Breast Cancer

Abstract Background: HER2 targeted therapy (tx) has transformed the trajectory of HER2+ metastatic breast cancer (MBC), with a subgroup of pts remaining on first line (1L) tx for many years (yrs). Detection of minimal residual disease (MRD) via ctDNA to guide tx is promising but data supporting its use in HER2+ MBC are virtually absent. Methods: We identified 70 pts with HER2+ MBC treated with 1L HER2 targeted tx consented to the EMBRACE cohort study with archival tissue, buffy coat and plasma at ≥1 key timepoints while on 1L tx (baseline, first-on-tx, year [Y] 1 landmark [L], Y2L, Y3L), or at time of disease progression (PD). We employed MAESTRO, an ultrasensitive whole-genome, tumor-informed, mutation enrichment sequencing assay, in a pooled testing format (MAESTRO-Pool). Exceptional responders were pts without PD or death for ≥3 yrs from 1L start (real-world progression-free survival [rwPFS] ≥3 yrs). Conventional responders were pts with PD or death within 3 yrs of 1L start (rwPFS