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ERBB2 (HER2), Gene Amplification

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Mass General Hospital Cancer Center treats patients with many cancer types. To learn more about the different cancer types that can be treated at the Cancer Center, please visit the Cancer Center website at the following page: http://www.massgeneral.org/cancer/services/
Expand Collapse ERBB2 (HER2)  - General Description ERBB2, often called HER2, is a gene that provides the code for making a cell surface protein called the ErbB2 (HER2) growth factor receptor. When certain growth factors (proteins that stimulate cell growth and division) bind to this receptor, they activate a signaling system inside the cell that ultimately promotes diverse functions such as growth, interaction and adhesion between cells, and ability of the cell to migrate within tissues. In some tumors, the activation of HER2 signaling is an important mechanism that drives the disease process. This can occur through HER2 gene amplification (the most common mechanism) or HER2 gene mutation in the cancer cells. Extra copies of the HER2 gene (gene amplification) have been found in a number of different cancers. This causes the cancer cells to make excess HER2 (overexpression), which in turn, tells the cells to grow and divide in an uncontrolled manner. The presence of amplified HER2 has been reported in approximately 25% of breast tumors, 20% of esophageal tumors, 15% of gastric cancers and 20% of certain ovarian tumors. The FDA has approved the targeted therapies including trastuzumab (Herceptin), pertuzumab (Perjeta), lapatinib (Tykerb), and T-DM1 (Kadcyla) for the treatment of patients with certain kinds of breast cancer in which HER2 is overexpressed. Trastuzumab is also FDA approved to treat gastric cancer with amplification of this receptor. Mutations in HER2 involving small duplications of the gene can promote resistance to some EGFR targeted therapies, but on the other hand, promote response to certain HER2 inhibitors. While very rare, these mutations are most often associated with non-small cell lung cancer, but have also been described in other malignancies including brain, gastric, breast and ovarian tumors. Tumor mutation profiling performed clinically at the MGH Cancer Center has identified HER2 mutations in a small subset of non-HER2 amplified breast cancer (1%) and non-small cell lung cancers (1%). Source: Genetics Home ReferenceThe ERBB2 gene encodes for a cell surface protein that belongs to the ERBB family of receptor tyrosine kinases, known as ErbB2 (more commonly referred to as HER2). Four members of the ERBB family have been identified; EGFR (ERBB1, HER1), ERBB2 (HER2), ERBB3 (HER3) and ERBB4 (HER4). Binding of a ligand induces ERBB receptor homo-/hetero-dimerization and triggers a signaling cascade that drives many cellular responses. These include the activation of PI3K/AKT/mTOR and MAP kinase/ERK pathways, which promote cell survival and proliferation. Although there is no known ligand for HER2, HER2 is the preferred dimerization partner for the other ERBB receptors. In some cancers, HER2 activity is increased through protein overexpression or gene mutation. The overexpression of HER2 is tightly associated with amplification of the HER2 gene. HER2 amplification has been reported in multiple malignancies, including breast cancer (25% incidence), esophageal cancer (20% incidence), gastric cancer (15% incidence), and mucinous ovarian carcinomas (20% incidence). Mutations in HER2 have also been identified as an important mechanism that could drive tumor growth and confer resistance to targeted therapies. In-frame duplication/insertions in a region of HER2 exon 20 that is conserved with EGFR have been demonstrated in ~2% of lung cancer patients. Mutations in HER2 receptor have also been described in a small subset of non-HER2 amplified breast cancer (1%). Source: Genetics Home Reference
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ERBB2, often called HER2, is a gene that provides the code for making a cell surface protein called the ErbB2 (HER2) growth factor receptor. When certain growth factors (proteins that stimulate cell growth and division) bind to this receptor, they activate a signaling system inside the cell that ultimately promotes diverse functions such as growth, interaction and adhesion between cells, and ability of the cell to migrate within tissues. In some tumors, the activation of HER2 signaling is an important mechanism that drives the disease process. This can occur through HER2 gene amplification (the most common mechanism) or HER2 gene mutation in the cancer cells.

Extra copies of the HER2 gene (gene amplification) have been found in a number of different cancers. This causes the cancer cells to make excess HER2 (overexpression), which in turn, tells the cells to grow and divide in an uncontrolled manner. The presence of amplified HER2 has been reported in approximately 25% of breast tumors, 20% of esophageal tumors, 15% of gastric cancers and 20% of certain ovarian tumors. The FDA has approved the targeted therapies including trastuzumab (Herceptin), pertuzumab (Perjeta), lapatinib (Tykerb), and T-DM1 (Kadcyla) for the treatment of patients with certain kinds of breast cancer in which HER2 is overexpressed. Trastuzumab is also FDA approved to treat gastric cancer with amplification of this receptor.

Mutations in HER2 involving small duplications of the gene can promote resistance to some EGFR targeted therapies, but on the other hand, promote response to certain HER2 inhibitors. While very rare, these mutations are most often associated with non-small cell lung cancer, but have also been described in other malignancies including brain, gastric, breast and ovarian tumors. Tumor mutation profiling performed clinically at the MGH Cancer Center has identified HER2 mutations in a small subset of non-HER2 amplified breast cancer (1%) and non-small cell lung cancers (1%).

Source: Genetics Home Reference
The ERBB2 gene encodes for a cell surface protein that belongs to the ERBB family of receptor tyrosine kinases, known as ErbB2 (more commonly referred to as HER2). Four members of the ERBB family have been identified; EGFR (ERBB1, HER1), ERBB2 (HER2), ERBB3 (HER3) and ERBB4 (HER4). Binding of a ligand induces ERBB receptor homo-/hetero-dimerization and triggers a signaling cascade that drives many cellular responses. These include the activation of PI3K/AKT/mTOR and MAP kinase/ERK pathways, which promote cell survival and proliferation. Although there is no known ligand for HER2, HER2 is the preferred dimerization partner for the other ERBB receptors. In some cancers, HER2 activity is increased through protein overexpression or gene mutation.

The overexpression of HER2 is tightly associated with amplification of the HER2 gene. HER2 amplification has been reported in multiple malignancies, including breast cancer (25% incidence), esophageal cancer (20% incidence), gastric cancer (15% incidence), and mucinous ovarian carcinomas (20% incidence).

Mutations in HER2 have also been identified as an important mechanism that could drive tumor growth and confer resistance to targeted therapies. In-frame duplication/insertions in a region of HER2 exon 20 that is conserved with EGFR have been demonstrated in ~2% of lung cancer patients. Mutations in HER2 receptor have also been described in a small subset of non-HER2 amplified breast cancer (1%).

Source: Genetics Home Reference
PubMed ID's
15864276, 9130710, 15457249, 16397024, 18772890, 16843263, 16988931, 22899400
Expand Collapse Gene Amplification  in ERBB2 (HER2)
Gene amplification occurs when a region of DNA that contains a gene is duplicated. Amplification of the ERBB2 (HER2) gene has been tightly linked to overexpression of the HER2 protein in cancer cells.
Gene amplification occurs when a region of DNA that contains a gene is duplicated. Amplification of the ERBB2 (HER2) gene has been tightly linked to overexpression of the HER2 protein in cancer cells.

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Your Matched Clinical Trials

Trial Matches: (G) - Gene, (M) - Mutation
Trial Status: Showing all 6 results Per Page:
Protocol # Title Location Status Match
NCT01953926 An Open-label, Phase 2 Study of Neratinib in Patients With Solid Tumors With Somatic Human Epidermal Growth Factor Receptor (EGFR, HER2, HER3) Mutations or EGFR Gene Amplification An Open-label, Phase 2 Study of Neratinib in Patients With Solid Tumors With Somatic Human Epidermal Growth Factor Receptor (EGFR, HER2, HER3) Mutations or EGFR Gene Amplification MGH Open GM
NCT01494662 HKI-272 for HER2-Positive Breast Cancer and Brain Metastases HKI-272 for HER2-Positive Breast Cancer and Brain Metastases MGH Open GM
NCT02491099 A Phase II Evaluation of Afatinibin Patients With Persistent or Recurrent HER2-positive Uterine Serous Carcinoma A Phase II Evaluation of Afatinibin Patients With Persistent or Recurrent HER2-positive Uterine Serous Carcinoma MGH Open G
NCT02716116 A Trial of AP32788 in Non-Small Cell Lung Cancer A Trial of AP32788 in Non-Small Cell Lung Cancer MGH Open G
NCT02260531 Cabozantinib +/- Trastuzumab In Breast Cancer Patients w/ Brain Metastases Cabozantinib +/- Trastuzumab In Breast Cancer Patients w/ Brain Metastases MGH Open G
NCT02326974 T-DM1+Pertuzumab in Pre-OP Early-Stage HER2+ BRCA T-DM1+Pertuzumab in Pre-OP Early-Stage HER2+ BRCA MGH Open G
MGH has many open clinical trials for other cancers not shown on the Targeted Cancer Care website. They can be found on the MassGeneral.org clinical trials search page.

Additional clinical trials may be applicable to your search criteria, but they may not be available at MGH. These clinical trials can typically be found by searching the clinicaltrials.gov website.
Trial Status: Showing all 6 results Per Page:

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