Stemness-Associated Biomarkers in Breast Cancer Liver Metastasis: Hepatic Adaptation, Prognostic Relevance, and Monitoring

The clinical assessment, treatment, and prognostic evaluation of breast cancer liver metastasis (BCLM) remain clinically challenging. Hepatic involvement is often identified only after substantial intrahepatic tumor burden, radiologically evident parenchymal involvement, abnormal liver function, or symptoms attributable to hepatic impairment have developed. Standard evaluation relies on molecular subtype, tumor burden, liver function, imaging, metastatic-site biopsy, receptor reassessment, and selected genomic testing; however, these variables do not fully explain why only a subset of disseminated tumor cells survives within the hepatic microenvironment, persists after therapy, and contributes to liver-dominant recurrence. This review examines CD44/CD24 phenotypic states, aldehyde dehydrogenase (ALDH) activity and isoform-specific expression, epithelial cell adhesion molecule (EpCAM)-positive and heterogeneous circulating tumor cells, claudin-2-associated hepatic tropism, and cellular interactions within the liver metastatic niche. We discuss how stemness-associated phenotypes may aid in interpreting delayed detectability, residual-cell persistence, treatment tolerance, and hepatic recurrence, while emphasizing that no single marker is sufficient for clinical stratification. Tissue reassessment, liquid biopsy, imaging, and clinicopathological information should be interpreted as complementary layers. Further progress requires BCLM-specific prospective cohorts, standardized tissue- and blood-based assays, paired primary and metastatic samples, serial liquid biopsy, and liver-specific endpoints that link residual disease biology to clinically meaningful monitoring and management.