Novel biomarkers in breast cancer for precision therapy and adaptive treatment strategies

Abstract Breast cancer is a biologically heterogeneous disease in which clinical outcomes are strongly influenced by molecular characteristics that guide therapeutic decision-making. While the traditional framework based on estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) has enabled major advances in patient stratification, it provides only a limited and static representation of tumor biology. Increasing evidence indicates that breast cancer evolves dynamically under therapeutic pressure, necessitating biomarkers that capture baseline tumor features while also reflecting adaptive molecular changes over time. Recent advances have expanded the biomarker landscape to include clinically actionable genomic alterations, such as PIK3CA and ESR1 mutations, as well as composite signatures reflecting DNA repair deficiency, immune activation, and functional transcriptional states. Liquid biopsy approaches, particularly circulating tumor DNA analysis, enable real-time monitoring of tumor resistance mechanism evolution, supporting a shift toward longitudinal biomarker assessment. In parallel, biomarkers derived from the tumor microenvironment—including immune gene expression signatures—are emerging as predictors of response to immunotherapy, often outperforming single-marker assays. Despite these advances, significant challenges remain in translating complex biomarker data into clinically actionable strategies, including issues of standardization, validation, and context-dependent interpretation. The most promising future directions lie in the integration of multi-modal biomarker platforms and the development of predictive models that reflect the evolving biology of the disease. Collectively, these developments support a paradigm shift in which biomarkers guide adaptive, personalized treatment strategies in breast cancer.