Circulating tumor DNA (ctDNA) has emerged as a pivotal biomarker in oncology, particularly for assessing tumor burden and predicting treatment outcomes. In a study focusing on high-risk early-stage HER2-negative breast cancer, ctDNA analysis demonstrated higher positivity rates in triple-negative breast cancer (TNBC) compared to hormone receptor-positive cases during neoadjuvant chemotherapy (NAC), suggesting subtype-specific differences in ctDNA shedding (ref: Magbanua doi.org/10.1016/j.ccell.2023.04.008/). Another study highlighted that a high baseline ctDNA copy number aberration (CNA) burden is a strong predictor of poor overall survival in metastatic breast cancer, reinforcing the prognostic significance of ctDNA in clinical settings (ref: Kim doi.org/10.1093/jnci/). Furthermore, ctDNA's role extends beyond breast cancer; it is also crucial in colorectal cancer, where molecular profiling through ctDNA can provide insights into targeted therapies and immunotherapy efficacy, emphasizing the need for genomics-guided precision medicine (ref: Guo doi.org/10.1053/j.gastro.2023.04.029/). Overall, these studies collectively underscore the potential of ctDNA as a non-invasive tool for monitoring treatment response and guiding therapeutic decisions across various cancer types, while also revealing the complexities of tumor biology and treatment resistance mechanisms.