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

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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 mutations in either the BRCA1 or BRCA2 gene confer an increased risk of breast and/or ovarian cancer. In addition, mutation carriers may be at increased risk of other primary cancers. Genetic testing is available to detect mutations in members of high-risk families. Such individuals should first be referred for counseling. Breast cancer is commonly treated by various combinations of surgery, radiation therapy, chemotherapy and hormone therapy.

Over the past years, significant major strides in understanding the biology of breast cancer have translated into actionable targeted therapies. For metastatic hormone receptor positive breast cancer, FDA approved therapies include tamoxifen, a selective estrogen modulator, aromatase inhibitors including exemestane, letrozole, and anastrozole, fulvestrant, a selective estrogen receptor blocker, and more recently everoliumus, a mTOR inhibitor, in combination with exemestane.

Despite significant improvements in the treatment of breast tumors, novel therapies and treatment strategies are needed. There are a number of novel therapies in development tailored to specific somatic mutations in the tumor.

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 mutations in either the BRCA1 or BRCA2 gene confer an increased risk of breast and/or ovarian cancer. In addition, mutation carriers may be at increased risk of other primary cancers. Genetic testing is available to detect mutations in members of high-risk families. Such individuals should first be referred for counseling. Breast cancer is commonly treated by various combinations of surgery, radiation therapy, chemotherapy and hormone therapy.

Over the past years, significant major strides in understanding the biology of breast cancer have translated into actionable targeted therapies. For metastatic hormone receptor positive breast cancer, FDA approved therapies include tamoxifen, a selective estrogen modulator, aromatase inhibitors including exemestane, letrozole, and anastrozole, fulvestrant, a selective estrogen receptor blocker, and more recently everoliumus, a mTOR inhibitor, in combination with exemestane.

Despite significant improvements in the treatment of breast tumors, novel therapies and treatment strategies are needed. There are a number of novel therapies in development tailored to specific somatic mutations in the tumor.

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 mutations in either the BRCA1 or BRCA2 gene confer an increased risk of breast and/or ovarian cancer. In addition, mutation carriers may be at increased risk of other primary cancers. Genetic testing is available to detect mutations in members of high-risk families. Such individuals should first be referred for counseling. Breast cancer is commonly treated by various combinations of surgery, radiation therapy, chemotherapy and hormone therapy.

Over the past years, significant major strides in understanding the biology of breast cancer have translated into actionable targeted therapies. For metastatic hormone receptor positive breast cancer, FDA approved therapies include tamoxifen, a selective estrogen modulator, aromatase inhibitors including exemestane, letrozole, and anastrozole, fulvestrant, a selective estrogen receptor blocker, and more recently everoliumus, a mTOR inhibitor, in combination with exemestane.

Despite significant improvements in the treatment of breast tumors, novel therapies and treatment strategies are needed. There are a number of novel therapies in development tailored to specific somatic mutations in the tumor.

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 mutations in either the BRCA1 or BRCA2 gene confer an increased risk of breast and/or ovarian cancer. In addition, mutation carriers may be at increased risk of other primary cancers. Genetic testing is available to detect mutations in members of high-risk families. Such individuals should first be referred for counseling. Breast cancer is commonly treated by various combinations of surgery, radiation therapy, chemotherapy and hormone therapy.

Over the past years, significant major strides in understanding the biology of breast cancer have translated into actionable targeted therapies. For metastatic hormone receptor positive breast cancer, FDA approved therapies include tamoxifen, a selective estrogen modulator, aromatase inhibitors including exemestane, letrozole, and anastrozole, fulvestrant, a selective estrogen receptor blocker, and more recently everoliumus, a mTOR inhibitor, in combination with exemestane.

Despite significant improvements in the treatment of breast tumors, novel therapies and treatment strategies are needed. There are a number of novel therapies in development tailored to specific somatic mutations in the tumor.

Source: National Cancer Institute, 2017
Expand Collapse ERBB3 (HER3)  - General Description
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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
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Your Matched Clinical Trials

Trial Matches: (D) - Disease, (G) - Gene, (M) - Mutation
Trial Status: Showing Results: 1-10 of 41 Per Page:
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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 DG
NCT01296555 A Dose Escalation Study Evaluating the Safety and Tolerability of GDC-0032 in Participants With Locally Advanced or Metastatic Solid Tumors or Non-Hodgkin's Lymphoma (NHL) and in Combination With Endocrine Therapy in Locally Advanced or Metastatic Hormone Receptor-Positive Breast Cancer A Dose Escalation Study Evaluating the Safety and Tolerability of GDC-0032 in Participants With Locally Advanced or Metastatic Solid Tumors or Non-Hodgkin's Lymphoma (NHL) and in Combination With Endocrine Therapy in Locally Advanced or Metastatic Hormone Receptor-Positive Breast Cancer MGH Open D
NCT02052778 A Dose Finding Study Followed by a Safety and Efficacy Study in Patients With Advanced Solid Tumors or Multiple Myeloma With FGF/FGFR-Related Abnormalities A Dose Finding Study Followed by a Safety and Efficacy Study in Patients With Advanced Solid Tumors or Multiple Myeloma With FGF/FGFR-Related Abnormalities MGH Open D
NCT02580448 A Open-Label Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Efficacy of VT-464 in Patients With Advanced Breast Cancer A Open-Label Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Efficacy of VT-464 in Patients With Advanced Breast Cancer MGH Open D
NCT02715284 A Phase 1 Dose Escalation and Cohort Expansion Study of TSR-042, an Anti-PD-1 Monoclonal Antibody, in Patients With Advanced Solid Tumors A Phase 1 Dose Escalation and Cohort Expansion Study of TSR-042, an Anti-PD-1 Monoclonal Antibody, in Patients With Advanced Solid Tumors MGH Open D
NCT02099058 A Phase 1/1b Study With ABBV-399, an Antibody Drug Conjugate, in Subjects With Advanced Solid Cancer Tumors A Phase 1/1b Study With ABBV-399, an Antibody Drug Conjugate, in Subjects With Advanced Solid Cancer Tumors MGH Open D
NCT02338349 A Phase I, Multicenter, Open-Label, Two-Part, Dose-escalation Study of RAD1901 in Postmenopausal Women With Advanced Estrogen Receptor Positive and HER2-Negative Breast Cancer A Phase I, Multicenter, Open-Label, Two-Part, Dose-escalation Study of RAD1901 in Postmenopausal Women With Advanced Estrogen Receptor Positive and HER2-Negative Breast Cancer MGH Open D
NCT01525589 A Phase II Clinical Trial of PM01183 in BRCA 1/2-Associated or Unselected Metastatic Breast Cancer A Phase II Clinical Trial of PM01183 in BRCA 1/2-Associated or Unselected Metastatic Breast Cancer MGH Open D
NCT02467361 A Study of BBI608 Administered in Combination With Immune Checkpoint Inhibitors in Adult Patients With Advanced Cancers A Study of BBI608 Administered in Combination With Immune Checkpoint Inhibitors in Adult Patients With Advanced Cancers 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
Trial Status: Showing Results: 1-10 of 41 Per Page:
12345Next »
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