Liquid biopsies are tools to examine tumors released into the peripheral blood and include cell-free DNA, a fraction of which consists of circulating tumor DNA (ctDNA), circulating tumor cells (CTCs), exosomes, and/or proteins. Consistent across studies, shedding tumors can actively or passively release DNA or CTCs into the blood and are associated with worse clinical outcome compared with nonshedding tumors. In metastatic breast cancer, CTC enumeration, at a well-established threshold, stratifies patients鈥� disease into indolent and aggressive classifications across pathologic subtypes, serving as the most significant negative factor associated with overall survival in multivariate analysis.1 Similarly, a higher ctDNA mutant allele frequency is associated with worse outcome for patients with advanced breast cancer.2 Compared with metastatic disease, early-stage cancers have a lower tumor burden, which presents a challenge to identify tumors in the blood for patients without distant metastasis based on standard clinical and imaging assessments. Evaluation of this minimal residual disease (MRD) in the blood has the potential to change the treatment paradigm of early-stage cancers.