The current staging and classification systems of breast cancer and their pitfalls: Is it possible to integrate the complexity of this neoplasm into a unified staging system?

Breast cancer is one of the leading causes of cancer death in women worldwide due to its variable aggressiveness and high propensity to develop distant metastases. The staging can be performed clinically or pathologically, generating the stage stratification by the TNM (T - tumor size; N- lymph node metastasis; M - distant organ metastasis) system. However, cancers with virtually identical TNM characteristics can present highly contrasting behaviors due to the divergence of molecular profiles. This review focuses on the histopathological nuances and molecular understanding of breast cancer through the profiling of gene and protein expression, culminating in improvements promoted by the integration of this information into the traditional staging system. As a culminating point, it will highlight predictive statistical tools for genomic risks and decision algorithms as a possible solution to integrate the various systems because they have the potential to reduce the indications for such tests, serving as a funnel in association with staging and previous classification.