Advances in Early Breast Cancer Risk Profiling: From Histopathology to Molecular Technologies

SIMPLE SUMMARY: Risk stratification for early breast cancer (BC) is extremely relevant for tailoring clinical decisions but challenging due to the absence of comprehensive guidelines. Traditional criteria like tumor size, lymph node involvement, histological type, grade, lymphovascular invasion, and immune cell infiltration serve as significant prognostic indicators. Alongside hormone receptor, HER2, and BRCA1/2 testing, molecular subtyping through gene expression profiling offers valuable insights for personalized clinical decisions. “Omics” technologies, applicable to tissue and liquid biopsy samples, have expanded risk evaluation capabilities, with limitations due to the lack of prospective data in early BC. This research overview paper highlights the need for standardized methodologies and integrated pathological models across multiple analytical dimensions for earlu BC risk stratification. The aim is to provide a practical guide for histopathologists and molecular pathologists involved in early BC profiling. ABSTRACT: Early breast cancer (BC) is the definition applied to breast-confined tumors with or without limited involvement of locoregional lymph nodes. While risk stratification is essential for guiding clinical decisions, it can be a complex endeavor in these patients due to the absence of comprehensive guidelines. Histopathological analysis and biomarker assessment play a pivotal role in defining patient outcomes. Traditional histological criteria such as tumor size, lymph node involvement, histological type and grade, lymphovascular invasion, and immune cell infiltration are significant prognostic indicators. In addition to the hormone receptor, HER2, and—in specific scenarios—BRCA1/2 testing, molecular subtyping through gene expression profiling provides valuable insights to tailor clinical decision-making. The emergence of “omics” technologies, applicable to both tissue and liquid biopsy samples, has broadened our arsenal for evaluating the risk of early BC. However, a pressing need remains for standardized methodologies and integrated pathological models that encompass multiple analytical dimensions. In this study, we provide a detailed examination of the existing strategies for early BC risk stratification, intending to serve as a practical guide for histopathologists and molecular pathologists.