HER2enriched

HER2-enriched is a molecular subtype of breast cancer identified through gene expression profiling, most prominently by the PAM50 classifier. This subtype is defined by high expression of HER2-related genes, including ERBB2 and GRB7, and a broader pattern of proliferation-associated genes, while showing lower expression of luminal estrogen receptor–related genes. It is one of the intrinsic subtypes described alongside Luminal A, Luminal B, Basal-like, and Normal-like.

The HER2-enriched subtype is not defined solely by HER2 gene amplification or by receptor status. Many tumors classified as HER2-enriched have HER2 signaling pathway activation, but this pattern can occur with or without HER2 amplification as detected by routine clinical testing. Conversely, some HER2-amplified tumors may fall into other intrinsic subtypes, such as luminal B, depending on their global gene expression profile. In practice, HER2-enriched often, but not exclusively, corresponds to tumors that are ER-negative and PR-negative, and they tend to show higher proliferation rates and higher histologic grade.

Clinical implications center on understanding tumor biology and guiding research contexts. Historically, the HER2-enriched subtype carried a poorer prognosis compared with some luminal subtypes when untreated. With the advent of HER2-targeted therapies (for example, trastuzumab and pertuzumab), outcomes for HER2-driven cancers have substantially improved, including those within the HER2-enriched category. While PAM50 classification can inform research and experimental therapy decisions, routine treatment planning typically relies on established HER2 testing (IHC/FISH) and receptor status, with gene expression profiling playing a more exploratory or adjunct role.