HER2nonamplified

HER2 nonamplified refers to tumors in which the HER2 gene (ERBB2) is not amplified and, in common clinical practice, HER2-directed therapy is not indicated based on gene copy number. In oncology, HER2 status is determined by assessing gene copy number through in situ hybridization tests and protein expression by immunohistochemistry. Nonamplified disease encompasses tumors that do not show HER2 gene amplification by fluorescence in situ hybridization (FISH) or equivalent assays, and that typically exhibit little to no HER2 protein overexpression by immunohistochemistry (IHC 0 or 1+). A subset with IHC 2+ requires FISH to confirm amplification; a negative FISH result in this category supports a nonamplified status.

Testing and interpretation often follow established guidelines from bodies such as the American Society of Clinical Oncology and the College of American Pathologists (ASCO/CAP). IHC assesses surface receptor protein levels, while FISH (or chromogenic in situ hybridization) evaluates gene copy number. The combination of these tests determines whether a tumor is HER2-amplified, HER2-nonamplified, or in the intermediate range. In many settings, HER2-nonamplified tumors are classified as HER2-negative, guiding treatment away from trastuzumab- or pertuzumab-based regimens.

Clinical implications are that standard anti-HER2 therapies are not typically used for HER2-nonamplified cancers. However, the emergence of targeted approaches for the HER2-low category (generally IHC 1+ or 2+ with negative FISH) has introduced potential therapeutic avenues in some cancers, reflecting evolving definitions of HER2-associated targets. Research continues to refine the distinctions between HER2-nonamplified and low-expressing tumors and their responses to novel agents.