[8] Amplification or over-expression of this oncogene has been shown to play an important role in the development and progression of certain aggressive types of breast cancer.

In recent years the protein has become an important biomarker and target of therapy for approximately 30% of breast cancer patients.

[15] Dimerisation results in the autophosphorylation of tyrosine residues within the cytoplasmic domain of the receptors and initiates a variety of signaling pathways.

[25] HER2 is colocalised and most of the time, coamplified with the gene GRB7, which is a proto-oncogene associated with breast, testicular germ cell, gastric, and esophageal tumours.

[29] The high amplification of HER2 copy number positively contributes to the survival time of gastric cardia adenocarcinoma patients.

Substitution of a valine for a glutamic acid or a glutamine in the transmembrane domain can result in the constitutive dimerisation of this protein in the absence of a ligand.

[35] Another monoclonal antibody, Pertuzumab, which inhibits dimerisation of HER2 and HER3 receptors, was approved by the FDA for use in combination with trastuzumab in June 2012.

As of November 2015, there are a number of ongoing and recently completed clinical trials of novel targeted agents for HER2+ metastatic breast cancer, e.g.

It has been found that patients with ER+ (Estrogen receptor positive)/HER2+ compared with ER-/HER2+ breast cancers may actually benefit more from drugs that inhibit the PI3K/AKT molecular pathway.

However, when the ratio of the coactivator AIB-3 exceeds that of the corepressor PAX2, the expression of HER2 is upregulated in the presence of tamoxifen, leading to tamoxifen-resistant breast cancer.

[38][39] Among approved anti-HER2 therapeutics are also tyrosine kinase inhibitors (Lapatinib, Neratinib, and Tucatinib) and antibody-drug conjugates (ado-trastuzumab emtansine and trastuzumab deruxtecan).

Micrographs showing each score:[46] FISH can be used to measure the number of copies of the gene which are present and is thought to be more reliable than immunohistochemistry.

Measurement of serum HER2 by enzyme-linked immunosorbent assay (ELISA) offers a far less invasive method of determining HER2 status than a biopsy and consequently has been extensively investigated.