HER2neu

HER2/neu, also known as ERBB2, is a transmembrane receptor tyrosine kinase in the epidermal growth factor receptor (EGFR) family. It participates in signaling pathways that regulate cell growth, differentiation, and survival. In normal cells, HER2 activity is tightly controlled; in cancer, overexpression or amplification can drive unchecked signaling and tumor progression.

HER2 overexpression is most well known in breast cancer, where it occurs in about 15-20% of invasive cases, and is associated with a more aggressive disease course. It is also found in other cancers, including gastric, ovarian, and certain others. The status of HER2 is a key prognostic and predictive biomarker, guiding the use of targeted therapies. Assessment is typically performed on tumor tissue using immunohistochemistry (IHC) to measure protein levels and in situ hybridization (FISH, CISH) to detect gene amplification. An IHC result of 3+ or a positive gene amplification by ISH classifies a tumor as HER2-positive; an IHC 2+ result requires ISH confirmation.

Targeted therapies for HER2-positive cancers include monoclonal antibodies such as trastuzumab and pertuzumab, antibody-drug conjugates like trastuzumab emtansine (T-DM1), and small molecule tyrosine kinase inhibitors such as lapatinib, neratinib, and tucatinib. These treatments are used in neoadjuvant, adjuvant, and metastatic settings, often in combination with chemotherapy. Resistance and heterogeneity of HER2 expression can affect response, and treatment is associated with potential adverse effects, including cardiotoxicity with some HER2-directed agents.