The ZEST trial marks a pivotal moment in oncology, focusing on circulating tumor DNA (ctDNA) surveillance to detect molecular residual disease in breast cancer patients. This study explored whether Niraparib, a PARP inhibitor, could extend disease-free survival in patients with detectable ctDNA post-treatment but without visible signs of recurrence. The findings offer insights into both the potential and the limitations of using ctDNA for personalized cancer management.