Breast Cancer, ESR1, Gene Amplification

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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 ESR1  - General Description
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The ESR1 gene encodes an estrogen receptor, which is a ligand-activated transcription factor composed of hormone binding domain, DNA binding domain, and transcription activation domain. The protein localizes to the nucleus, where it forms homodimers, or heterodimerizes with ESR2. Transactivation in the nucleus involves either direct homodimer binding to an estrogen response element (ERE) sequence, or association with other DNA-binding transcription factors such as AP-1/c-Jun, c-Fos, ATF-2, Sp1 and Sp3 to mediate ERE-independent signaling. Mutual trans-repression occurs between the ESR and NF-kapa-B in a cell-type specific manner. Alternative promoter usage and alternative splicing result in dozens of transcript variants, but the full length nature of many of these variants has not been determined. Estrogen and its receptors are essential for sexual development and reproductive function, but also play a role in other tissues such as bone.

Sources: Ref Sequence Mar 2014; NCBI Gene; UniProt;
The ESR1 gene encodes an estrogen receptor, which is a ligand-activated transcription factor composed of hormone binding domain, DNA binding domain, and transcription activation domain. The protein localizes to the nucleus, where it forms homodimers, or heterodimerizes with ESR2. Transactivation in the nucleus involves either direct homodimer binding to an estrogen response element (ERE) sequence, or association with other DNA-binding transcription factors such as AP-1/c-Jun, c-Fos, ATF-2, Sp1 and Sp3 to mediate ERE-independent signaling. Mutual trans-repression occurs between the ESR and NF-kapa-B in a cell-type specific manner. Alternative promoter usage and alternative splicing result in dozens of transcript variants, but the full length nature of many of these variants has not been determined. Estrogen and its receptors are essential for sexual development and reproductive function, but also play a role in other tissues such as bone.

Sources: Ref Sequence Mar 2014; NCBI Gene; UniProt;
PubMed ID's
24217577, 12496244, 24398047, 24583794
Expand Collapse Gene Amplification  in ESR1
A specific type of genetic alteration in which instead of one copy of a gene per cell, specific segments of the DNA containing the ESR1 gene are copied multiple times (amplified). The amplified ESR1 gene results in many more RNA transcripts of the gene from the multiple copies of the ESR1 coding DNA, which are then translated into the ER protein at a much higher level than is found in normal cells. This overexpression of amplified proteins has been found in a subset of breast cancers.
A specific type of genetic alteration in which instead of one copy of a gene per cell, specific segments of the DNA containing the ESR1 gene are copied multiple times (amplified). The amplified ESR1 gene results in many more RNA transcripts of the gene from the multiple copies of the ESR1 coding DNA, which are then translated into the ER protein at a much higher level than is found in normal cells. This overexpression of amplified proteins has been found in a subset of breast cancers.

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Your Matched Clinical Trials

Trial Matches: (D) - Disease, (G) - Gene, (M) - Mutation
Trial Status: Showing Results: 1-10 of 39 Per Page:
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Protocol # Title Location Status Match
NCT01971515 First-in-Human Dose Escalation Trial in Subjects With Advanced Malignancies First-in-Human Dose Escalation Trial in Subjects With Advanced Malignancies MGH Open DGM
NCT02316509 Study of SRN-927 in Postmenopausal Women With Locally Advanced or Metastatic Estrogen Receptor Positive Breast Cancer Study of SRN-927 in Postmenopausal Women With Locally Advanced or Metastatic Estrogen Receptor Positive Breast Cancer MGH Open DGM
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 DG
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 DG
NCT02684032 A Study To Assess The Tolerability And Clinical Activity Of Gedatolisib In Combination With Palbociclib/Letrozole Or Palbociclib/Fulvestrant In Women With Metastatic Breast Cancer A Study To Assess The Tolerability And Clinical Activity Of Gedatolisib In Combination With Palbociclib/Letrozole Or Palbociclib/Fulvestrant In Women With Metastatic Breast Cancer MGH Open DG
NCT02734615 Phase I/Ib Trial of LSZ102 Single Agent or LSZ102 + LEE011 or LSZ102 + BYL719 in ER+ Breast Cancers Phase I/Ib Trial of LSZ102 Single Agent or LSZ102 + LEE011 or LSZ102 + BYL719 in ER+ Breast Cancers MGH Open DG
NCT01872260 Study of LEE011, BYL719 and Letrozole in Advanced ER+ Breast Cancer Study of LEE011, BYL719 and Letrozole in Advanced ER+ Breast Cancer MGH Open DG
NCT02732119 Study of Ribociclib With Everolimus + Exemestane in HR+ HER2- Locally Advanced/Metastatic Breast Cancer Post Progression on CDK 4/6 Inhibitor. Study of Ribociclib With Everolimus + Exemestane in HR+ HER2- Locally Advanced/Metastatic Breast Cancer Post Progression on CDK 4/6 Inhibitor. 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
Trial Status: Showing Results: 1-10 of 39 Per Page:
1234Next »
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