HER2Überexpression

HER2 overexpression, sometimes written as HER2-Überexpression in German-language texts, refers to abnormally high levels of the HER2 protein on the surface of cells. HER2 is a receptor tyrosine kinase in the epidermal growth factor receptor family and is encoded by the ERBB2 gene on chromosome 17. In cancers, particularly breast cancer, ERBB2 amplification or other regulatory changes lead to excessive, often constitutively active HER2 that stimulates signaling pathways such as PI3K–Akt and MAPK, promoting cell growth, survival, and invasion.

In breast cancer, HER2 positivity is defined by protein overexpression or gene amplification. About 15–20% of invasive breast cancers harbor HER2 amplification/overexpression. Clinically, HER2-positive tumors were historically associated with poorer prognosis, but outcomes have improved substantially with anti-HER2 targeted therapies.

Diagnosis relies on immunohistochemistry (IHC) and in situ hybridization methods. IHC assesses protein expression levels (scores 0–3+), with 3+ considered positive. A 2+ score is equivocal and typically confirmed by fluorescence in situ hybridization (FISH) for ERBB2 gene amplification. Testing adheres to guidelines from professional bodies (e.g., ASCO/CAP) to ensure accuracy and consistency.

Therapy centers on anti-HER2 agents, including monoclonal antibodies such as trastuzumab and pertuzumab, antibody–drug conjugates like ado-trastuzumab emtansine (T-DM1), and tyrosine kinase inhibitors such as lapatinib and neratinib. Treatment aims to combine HER2 blockade with chemotherapy, monitor for cardiac toxicity, and address resistance mechanisms, including downstream pathway alterations.

HER2 overexpression also occurs in other cancers, notably gastric/GEJ adenocarcinoma, where testing guides the use of trastuzumab in certain metastatic cases.