A perspective on the development and lack of interchangeability of the breast cancer intrinsic subtypes

Breast cancer intrinsic subtypes (IS) are biologically distinct entities, characterized by specific natural gene expression patterns. The most widely accepted IS are the Luminal A, Luminal B, HER2-Enriched, and Basal-like (Fig. 1). These entities are prognostic and have potential therapeutic implications in both early-stage and advanced-stage hormone receptor-positive (HR+)/HER2-negative breast cancer. However, the IS molecular classification is often misinterpreted, and immunohistochemistry (IHC)-based IS surrogates, or other molecular subtype definitions, are erroneously used interchangeably. This generates confusion for all the stakeholders involved, including scientists studying these biomarkers and physicians considering them for clinical decision-making. In this perspective, therefore, we provide readers with a historical overview of the discovery and clinical implementation of the IS, the main technical and biological differences among assays developed for their detection, and propose a specific and simple nomenclature for subtyping to avoid further confusion and disservice to patients.