Breast Cancer, ESR1

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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 (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 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 ESR1  in Breast Cancer
In addition to Estrogen Receptor’s normal role in sexual development, metabolism and bone development, ESR's are also involved in pathological processes including breast cancer. ESR1 is the gene that encodes the protein ESR alpha, which has been found to have a role in breast cancer. The following genetic alterations in the ESR1 gene have been found through the analysis of many indvidual breast tumors: Mutations in the Ligand-Binding Domain, or LBD (the part of the ESR alpha protein which binds to the hormone estrogen); a loss of ESR1 expression; Altered activity of Co-regulatory proteins of ESR1; Cross-talk between ER alpha and growth factor signal pathways in tumor cells; and ESR1 gene amplification. How each of these types of genetic alterations contributes to the development of breast cancer is currently under study.

Normally, ER alpha binds to its’ ligand, estrogen hormone, on part of the protein that is encoded by two segments of the genetic code in DNA, called codon 537 and codon 538. Together, these code the sequence for Ligand Binding Domain (LBD). When estrogen binds to ER alpha on the LBD, a conformational change in the protein takes place, which activates ER alpha to “turn on” specific genes in the nucleus of cells. Therefore, in ER-positive breast cancers, oncologists prescribe various anti-estrogen therapies, such as tamoxifen and fulvestrant, to inhibit cancer growth.

Some ER+ patients who have been treated with endocrine therapies eventually develop resistance, and their cancers progress. A subset of the patients who have developed resistance to endocrine therapies, mutations have been found in the LBD of ESR1, specifically in codons 537 and 538. In structural modeling studies of the LBD mutants, it has been shown that these mutations cause similar conformational changes to those induced by activated ligand-bound receptor. In other words, even in the absence of the ligand estrogen, because of the mutation in the LBD, the protein adopts the “active” conformation. Laboratory experiments have shown that these LBD mutant ESR1 proteins activate transcription and proliferation as if there were ligand present, and that they have reduced interaction with anti-estrogen therapies, such as tamoxifen and fulvestrant. LBD ESR1 mutations are found almost exclusively in patients who have been treated with hormone therapy, and they are found more frequently in patients who have had multiple rounds of hormone therapies.

In addition to Estrogen Receptor’s normal role in sexual development, metabolism and bone development, ESR's are also involved in pathological processes including breast cancer. ESR1 is the gene that encodes the protein ESR alpha, which has been found to have a role in breast cancer. The following genetic alterations in the ESR1 gene have been found through the analysis of many indvidual breast tumors: Mutations in the Ligand-Binding Domain, or LBD (the part of the ESR alpha protein which binds to the hormone estrogen); a loss of ESR1 expression; altered activity of Co-regulatory proteins of ESR1; Cross-talk between ER alpha and growth factor signal pathways in tumor cells; and ESR1 gene amplification. How each of these types of genetic alterations contributes to the development of breast cancer is currently under study.

Normally, ER alpha binds to its’ ligand, estrogen hormone, on part of the protein that is encoded by two segments of the genetic code in DNA, called codon 537 and codon 538. Together, these code the sequence for Ligand Binding Domain (LBD). When estrogen binds to ER alpha on the LBD, a conformational change in the protein takes place, which activates ER alpha to “turn on” specific genes in the nucleus of cells. Therefore, in ER-positive breast cancers, oncologists prescribe various anti-estrogen therapies, such as tamoxifen and fulvestrant, to inhibit cancer growth.

Some ER+ patients who have been treated with endocrine therapies eventually develop resistance, and their cancers progress. In a subset of the patients who have developed resistance to endocrine therapies, mutations have been found in the LBD of ESR1, specifically in codons 537 and 538. In structural modeling studies of the LBD mutants, it has been shown that these mutations cause similar conformational changes to those induced by activated ligand-bound receptor. In other words, even in the absence of the ligand estrogen, because of the mutation in the LBD, the protein adopts the “active” conformation. Laboratory experiments have shown that these LBD mutant ESR1 proteins activate transcription and proliferation as if there were ligand present, and that they have reduced interaction with anti-estrogen therapies, such as tamoxifen and fulvestrant. LBD ESR1 mutations are found almost exclusively in patients who have been treated with hormone therapy, and they are found more frequently in patients who have had multiple rounds of hormone therapies.

PubMed ID's
24398047
Expand Collapse No mutation selected
The mutation of a gene provides clinicians with a very detailed look at your cancer. Knowing this information could change the course of your care. To learn how you can find out more about genetic testing please visit http://www.massgeneral.org/cancer/news/faq.aspx or contact the Cancer Center.
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Your Matched Clinical Trials

Trial Matches: (D) - Disease, (G) - Gene
Trial Status: Showing all 9 results Per Page:
Protocol # Title Location Status Match
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
NCT01953926 Neratinib HER Mutation Basket Study (SUMMIT) Neratinib HER Mutation Basket Study (SUMMIT) 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:
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