Advances in prognostic and predictive biomarkers for breast cancer: Integrating multigene assays, hormone receptors, and emerging circulating biomarkers.

Breast cancer is a biologically diverse disease, and optimizing patient outcomes requires precise prognostic and predictive tools to guide treatment decisions. Over the past two decades, significant advances have been made in stratifying breast cancer risk through the integration of multigene assays, hormone receptor profiling, and emerging circulating biomarkers. This review outlines the current landscape and future direction of prognostic and predictive biomarker development. Combining specific multigene tests, biomarkers such as HER2/neu, and traditional clinicopathological prognostic factors is the most efficient way to determine prognosis. Well-established multigene assays such as Oncotype DX, MammaPrint, and uPA/PAI-1 are routinely employed to inform adjuvant treatment decisions in hormone receptor-positive, HER2-negative subtypes. Hormone receptor status (ER, PR) and HER2 expression continue to serve as cornerstone predictors of therapeutic response to endocrine and anti-HER2 therapies. Concurrently, a new generation of non-invasive biomarkers like circulating tumor DNA (ctDNA), microRNAs, and circulating tumor cells (CTCs) offers promise for real-time monitoring of treatment response and early detection of resistance, particularly in advanced disease. Notably, ESR1 mutations detected in ctDNA have emerged as potential indicators of resistance to aromatase inhibitors. Despite these advances, the identification of robust biomarkers to predict response to chemotherapy and radiotherapy remains a critical unmet need. This review synthesizes current evidence and highlights key challenges and opportunities in the clinical translation of biomarker-driven precision oncology for breast cancer.