HER2status

HER2status refers to the status of the human epidermal growth factor receptor 2 (HER2) in tumor cells, most commonly in breast cancer. HER2 is a transmembrane tyrosine kinase involved in growth signaling; its overexpression or gene amplification is associated with more aggressive disease but also with response to HER2-targeted therapies. Determining HER2status is essential for treatment planning and prognostication.

Testing methods and interpretation: HER2status is typically assessed on formalin-fixed tumor tissue. Immunohistochemistry (IHC) measures HER2 protein on tumor cell membranes and is scored 0, 1+, 2+, or 3+. Scores of 0 or 1+ are considered negative; 3+ is positive. An IHC score of 2+ is equivocal and requires in situ hybridization (ISH) testing to assess HER2 gene amplification (e.g., FISH, CISH, or SISH). A positive ISH result confirms HER2-positive status; negative findings with IHC 2+ are considered HER2-negative.

Clinical significance: HER2-positive tumors are eligible for HER2-targeted therapies, such as trastuzumab, pertuzumab, ado-trastuzumab emtansine, lapatinib, and other agents. In many settings, HER2 positivity is associated with improved response to targeted therapy but historically with more aggressive tumor biology if untreated. Guidelines from ASCO/CAP standardize testing and interpretation, including repeat testing of metastatic lesions when clinically indicated.

Limitations and considerations: Testing quality depends on tissue handling and fixation; intratumoral heterogeneity and changes between primary and metastatic sites can affect status. Retesting may be considered in advanced disease to guide therapy decisions. While most relevance is in breast cancer, similar testing is used in gastric and gastroesophageal cancers with site-specific criteria.