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

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.

Keywords: biomarkers; breast cancer; early breast cancer; prognostication; risk assessment.

Figure 1

The risk assessment of early breast cancer (BC) involves analyzing various biomarkers and clinicopathologic features. Traditional histopathological characteristics like tumor size, lymph node involvement, histological grade, and lymphovascular invasion form the core of the pathology report, offering essential prognostic information. Some pathologists may report TILs, especially in TNBC and HER2+ BC, although current recommendations do not suggest basing therapeutic strategies on TILs due to their lack of clinical utility. Immunohistochemical assessment of hormone receptor status, HER2 status, and Ki67 is equally vital, reflecting the luminal/non-luminal molecular classification and guiding treatment choices with both prognostic and predictive implications. Integrating gene profiling assays into early BC evaluation optimizes adjuvant treatment decisions, especially for post-menopausal luminal patients with or without 1–3 node metastases and pre-menopausal luminal patients without lymph node involvement. In cases suggestive of hereditary BC syndrome, BRCA1/2 testing is recommended. Abbreviations: BC, breast cancer; TILs, tumor-infiltrating lymphocytes; ER, estrogen receptor; PgR, progesterone receptor; TNBC, triple-negative BC.