HER2positive

HER2-positive refers to tumors that overexpress the human epidermal growth factor receptor 2 (HER2), typically due to amplification of the ERBB2 gene. HER2 is a receptor tyrosine kinase in the ERBB family, and its overexpression drives increased cellular signaling and proliferation. While most commonly discussed in breast cancer, HER2 positivity also occurs in a subset of gastric and gastroesophageal cancers and informs treatment decisions in those diseases as well.

HER2 status is determined by two main tests: immunohistochemistry (IHC) and in situ hybridization (ISH). An IHC score of 3+ is considered positive for overexpression; 0 or 1+ is negative; 2+ is equivocal and usually leads to reflex testing with FISH or other ISH methods to confirm gene amplification. Interpretation guidelines from professional organizations (such as ASCO/CAP) are used to standardize results. Pre-analytical factors and tumor heterogeneity can influence testing.

In breast cancer, about 15–20% of cases are HER2-positive. Overexpression or amplification of HER2 promotes aggressive tumor behavior, but it also creates a target for therapy. The advent of HER2-targeted treatments has markedly improved outcomes and transformed the prognosis for many patients with HER2-positive disease.

Therapy typically involves HER2-targeted agents, often in combination with chemotherapy. Trastuzumab, a monoclonal antibody, improved survival when added to standard regimens, and dual blockade with trastuzumab and pertuzumab further enhanced outcomes. Other therapies include antibody-drug conjugates (ado-trastuzumab emtansine, trastuzumab deruxtecan) and small-molecule tyrosine kinase inhibitors (lapatinib, neratinib, tucatinib). Cardiotoxicity risk necessitates monitoring of cardiac function during treatment. Ongoing research focuses on resistance mechanisms, optimal sequencing, and expanding benefits to additional cancer types and patient subgroups, including the evolving concept of HER2-low tumors.