Breast Cancer, ERBB3 (HER3), amplification, overexpression, mutation

View:
Expand Collapse Breast Cancer  - General Description Breast cancer is the most common non-cutaneous cancer among women in the United States. This year about 252,710 women in the U.S. will be told by a doctor that they have breast cancer. Half of these people will be at least 62 years old. However, an estimated 3,327,552 women are living with female breast cancer in the United States following treatment.

Germline (inherited) mutations in either the BRCA1 or BRCA2 gene confer an increased risk of breast and/or ovarian cancer to women. In addition, women and men carrying BRCA1 or BRCA2 mutations are at increased risk of developing other primary cancers. Genetic testing is available at the MGH genetics lab to detect mutations in members of high-risk families. Such individuals should also be referred for genetic counseling to obtain more information about the implications of inherited BRCA1 and BRCA2 mutations. Innovative treatments are available for patients with inherited BRCA1 or BRCA2 mutations at the MGH Cancer Center. There is also a large portfolio of clinical trials testing the newest treatments at the MGH Cancer Center.

Despite significant improvements in the treatment of breast tumors, new therapies and treatment strategies are needed to improve outcomes for breast cancer patients. There are a number of novel targeted therapies as well as new immuno-therapies being used that are tailored to individual patient mutations at the MGH Cancer Center.

Source: National Cancer Institute, 2017
Breast cancer is the most common non-cutaneous cancer among women in the United States. This year about 252,710 women in the U.S. will be told by a doctor that they have breast cancer. Half of these people will be at least 62 years old. However, an estimated 3,327,552 women are living with female breast cancer in the United States following treatment.

Germline (inherited) mutations in either the BRCA1 or BRCA2 gene confer an increased risk of breast and/or ovarian cancer to women. In addition, women and men carrying BRCA1 or BRCA2 mutations are at increased risk of developing other primary cancers. Genetic testing is available at the MGH genetics lab to detect mutations in members of high-risk families. Such individuals should also be referred for genetic counseling to obtain more information about the implications of inherited BRCA1 and BRCA2 mutations. Innovative treatments are available for patients with inherited BRCA1 or BRCA2 mutations at the MGH Cancer Center. There is also a large portfolio of clinical trials testing the newest treatments at the MGH Cancer Center.

Despite significant improvements in the treatment of breast tumors, new therapies and treatment strategies are needed to improve outcomes for breast cancer patients. There are a number of novel targeted therapies as well as new immuno-therapies being used that are tailored to individual patient mutations at the MGH Cancer Center.

Source: National Cancer Institute, 2017
Breast cancer is the most common non-cutaneous cancer among women in the United States. This year about 252,710 women in the U.S. will be told by a doctor that they have breast cancer. Half of these people will be at least 62 years old. However, an estimated 3,327,552 women are living with female breast cancer in the United States following treatment.

Germline (inherited) mutations in either the BRCA1 or BRCA2 gene confer an increased risk of breast and/or ovarian cancer to women. In addition, women and men carrying BRCA1 or BRCA2 mutations are at increased risk of developing other primary cancers. Genetic testing is available at the MGH genetics lab to detect mutations in members of high-risk families. Such individuals should also be referred for genetic counseling to obtain more information about the implications of inherited BRCA1 and BRCA2 mutations. Innovative treatments are available for patients with inherited BRCA1 or BRCA2 mutations at the MGH Cancer Center. There is also a large portfolio of clinical trials testing the newest treatments at the MGH Cancer Center.

Despite significant improvements in the treatment of breast tumors, new therapies and treatment strategies are needed to improve outcomes for breast cancer patients. There are a number of novel targeted therapies as well as new immuno-therapies being used that are tailored to individual patient mutations at the MGH Cancer Center.

Source: National Cancer Institute, 2017
Breast cancer is the most common non-cutaneous cancer among women in the United States. This year about 252,710 women in the U.S. will be told by a doctor that they have breast cancer. Half of these people will be at least 62 years old. However, an estimated 3,327,552 women are living with female breast cancer in the United States following treatment.

Germline (inherited) mutations in either the BRCA1 or BRCA2 gene confer an increased risk of breast and/or ovarian cancer to women. In addition, women and men carrying BRCA1 or BRCA2 mutations are at increased risk of developing other primary cancers. Genetic testing is available at the MGH genetics lab to detect mutations in members of high-risk families. Such individuals should also be referred for genetic counseling to obtain more information about the implications of inherited BRCA1 and BRCA2 mutations. Innovative treatments are available for patients with inherited BRCA1 or BRCA2 mutations at the MGH Cancer Center. There is also a large portfolio of clinical trials testing the newest treatments at the MGH Cancer Center.

Despite significant improvements in the treatment of breast tumors, new therapies and treatment strategies are needed to improve outcomes for breast cancer patients. There are a number of novel targeted therapies as well as new immuno-therapies being used that are tailored to individual patient mutations at the MGH Cancer Center.

Source: National Cancer Institute, 2017
Expand Collapse ERBB3 (HER3)  - General Description
CLICK IMAGE FOR MORE INFORMATION
ERBB3, often called HER3, is a gene that provides the code for making a cell surface protein called the ErbB3 (HER3) 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 the ability of the cell to migrate within tissues. In some tumors, the activation of HER3 signaling is an important mechanism that drives the disease process. This can occur through genetic alterations in the ERBB3 (HER3) gene including amplification, overexpression, or gene mutation in the cancer cells.

The ERBB3 (HER3) gene has been found to be genetically altered (gene amplification, overexpression, or mutation) in a number of different cancers. These include breast, stomach, ovary, prostate, colon, pancreas, oral cavity, and lung. The genetic alterations seen in ERBB3 (HER3) in cancers cause increased amounts of the receptor to be produced, or, in the case of mutations, cause the protein to be activated even in the absence of stimulation by growth factor-binding. The excess or activated ERBB3 (HER3) interacts with other members of the ERBB family of growth factor receptors, sending signals through a series of protein cascades in the cell that cause the cells to grow and divide in an uncontrolled manner. Genomic testing of tumors in labs such as the one at MGH can identify the presence of genetic alterations in ERBB3 (HER3), and help clinicians make appropriate decisions about treatment with therapeutic agents that target the ERBB3 (HER3) receptor itself, or that target the growth signal pathways activated by HER3 (ERBB3) and its’ family member partners. These drugs are currently being studied in clinical trials as treatments for patients with tumors harboring genetic alterations in HER3 (ERBB3). Pertuzumab is a drug that blocks HER2:HER3 dimerization and is FDA approved for treatment of HER2 positive breast cancer.

Scientific studies on tumors from patients has also demonstrated that ERBB3 (HER3) plays an important role in the development of resistance to cancer therapies, particularly anti-HER2 therapies and other targeted therapies modulating the PI3K/AKT/mTOR pathway and MAP kinase/ERK pathways in cancer. Patients who are initially treated and respond to some cancer therapies subsequently develop genetic alterations in ERBB3 (HER3), which play a central role in relapse or resistance to the initial treatment. More clinical studies are needed that identify strategies for preventing the emergence of resistance in patients to ERBB3 (HER3) therapy, and for improved treatment of tumors with identified ERBB3 (HER3) genetic alterations. Clinical trials directly targeting ERBB3 (HER3) are underway, as are therapies targeting downstream pathways that are activated by the receptor.

Source Genetics Home Reference
The ERBB3 (HER3) gene encodes a cell surface protein that belongs to the ERBB family of receptor tyrosine kinases, known as ErbB3 (more commonly referred to as HER3). Four members of the ERBB family have been identified; EGFR (ERBB1, HER1), ERBB2 (HER2), ERBB3 (HER3) and ERBB4 (HER4). The binding of a ligand induces ERBB receptor homo-/hetero-dimerization, which activates and subsequently 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 are several known ligands for ERBB3 (HER3) including neuregulin, ERBB3 (HER3) is an obligate heterodimerization partner with other ERBB family members, as the kinase domain is not functional. ERBB2 (HER2) is the preferred dimerization partner for ERBB3 (HER3), and this heterodimer is catalytically more active than any other dimerization pairing within the ERBB family. ERBB3 plays a role in normal embryogenesis, but is found to be genetically altered through amplification, overexpression, or mutation in a wide array of cancers including breast, stomach, ovary, prostate, colon, pancreas, oral cavity, and lung, among others.

Genetic alterations including amplification, overexpression, and mutations in ERBB3 (HER3) have also been identified as an important mechanism driving tumor growth, and also in conferring resistance to targeted therapies. Clinical trials directly targeting ERBB3 (HER3) are underway, as are therapies targeting downstream pathways activated by the receptor.

Source: Genetics Home Reference
PubMed ID's
23198146
Expand Collapse amplification, overexpression, mutation  in ERBB3 (HER3)
ERBB3 (HER3) genetic alterations including gene amplification, overexpression, and activating mutations have been found in breast cancer. The Center for Integrated Diagnostics at MGH is a sophisticated testing center that is able to identify these genetic alterations in patient tumors in its’ CLIA certified facility.

Clinical trials are now underway to investigate novel ERBB3 (HER3) inhibitors, as well as combination drug strategies targeting downstream signal pathways in cancer cells.
ERBB3 (HER3) genetic alterations including gene amplification, overexpression, and activating mutations have been found in breast cancer. The Center for Integrated Diagnostics at MGH is a sophisticated testing center that is able to identify these genetic alterations in patient tumors in its’ CLIA certified facility.

Clinical trials are now underway to investigate novel ERBB3 (HER3) inhibitors, as well as combination drug strategies targeting downstream signal pathways in cancer cells.


PubMed ID's
23198146
Our Breast Cancer Team

Share with your Physican

Print information for your Physician.

Print information

Your Matched Clinical Trials

Trial Matches: (D) - Disease, (G) - Gene, (M) - Mutation
Trial Status: Showing all 9 results Per Page:
Protocol # Title Location Status Match
NCT01953926 Neratinib HER Mutation Basket Study (SUMMIT) Neratinib HER Mutation Basket Study (SUMMIT) MGH Open DG
NCT02099058 A Study Evaluating the Safety, Pharmacokinetics (PK), and Preliminary Efficacy of ABBV-399 in Subjects With Advanced Solid Tumors A Study Evaluating the Safety, Pharmacokinetics (PK), and Preliminary Efficacy of ABBV-399 in Subjects With Advanced Solid Tumors MGH Open D
NCT01325441 A Study of BBI608 Administered With Paclitaxel in Adult Patients With Advanced Malignancies A Study of BBI608 Administered With Paclitaxel in Adult Patients With Advanced Malignancies MGH Open D
NCT02052778 A Study of TAS-120 in Patients With Advanced Solid Tumors A Study of TAS-120 in Patients With Advanced Solid Tumors MGH Open D
NCT02939274 An Open Label, Phase II Trial of Continuous Low-Irradiance Photodynamic Therapy (CLIPT) Using Verteporfin (Visudyne®) for the Treatment of Cutaneous Metastases of Breast Cancer An Open Label, Phase II Trial of Continuous Low-Irradiance Photodynamic Therapy (CLIPT) Using Verteporfin (Visudyne®) for the Treatment of Cutaneous Metastases of Breast Cancer MGH Open D
NCT02574455 ASCENT-Study of Sacituzumab Govitecan in Refractory/Relapsed Triple-Negative Breast Cancer ASCENT-Study of Sacituzumab Govitecan in Refractory/Relapsed Triple-Negative Breast Cancer MGH Open D
NCT02568267 Basket Study of Entrectinib (RXDX-101) for the Treatment of Patients With Solid Tumors Harboring NTRK 1/2/3 (Trk A/B/C), ROS1, or ALK Gene Rearrangements (Fusions) Basket Study of Entrectinib (RXDX-101) for the Treatment of Patients With Solid Tumors Harboring NTRK 1/2/3 (Trk A/B/C), ROS1, or ALK Gene Rearrangements (Fusions) MGH Open D
NCT01494662 HKI-272 for HER2-Positive Breast Cancer and Brain Metastases HKI-272 for HER2-Positive Breast Cancer and Brain Metastases MGH Open D
NCT01872975 Standard or Comprehensive Radiation Therapy in Treating Patients With Early-Stage Breast Cancer Previously Treated With Chemotherapy and Surgery Standard or Comprehensive Radiation Therapy in Treating Patients With Early-Stage Breast Cancer Previously Treated With Chemotherapy and Surgery MGH Open D
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 9 results Per Page:
Our Breast Cancer Team

Share with your Physican

Print information for your Physician.

Print information