Breast Cancer, FGFR 1, 2, 3 and 4

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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 FGFR 1, 2, 3 and 4  - General Description
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Fibroblast growth factors (FGF’s) are ligands that bind to FGF cell surface receptors (FGFR’s) and activate them. Once activated, FGFR’s on normal cells transmit a growth signal inside the cell. This growth signal is transmitted via two important pathways inside cells; the RAS-dependent MAP kinase pathway, and a second signal pathway that involves PI3K and AKT. There are four different FGFR’s that make up a family of FGFR tyrosine kinase cell surface receptors, each having an extracellular domain that binds FGF ligands, a second domain that goes through the cell outer membrane, and a third domain that is inside the cell cytoplasm (see diagram above). FGFR signaling in normal cells stimulates proliferation, differentiation, embryonic development, cell migration, survival, angiogenesis (vascularization), and organogenesis (organ development).

Recently, FGFR genetic abnormalities have been found in several types of cancer. There are four FGFR family members, FGFR1, FGFR2, FGFR3, and FGFR4. Alterations in FGFR genes result in dysregulated FGF receptors and can promote cancer growth and metastasis. In a recent study of almost 5000 tumors, alterations in FGFR were found in 7% of of tumors. Among these tumors, alterations were identified in all 4 FGFR’s including FGFR1 (49%), FGFR2 (19%), FGFR3 (23%), and FGFR4 (7%). A small number of the tumors had genetic alterations in more than one type of FGFR. Clearly cancers have found a way to take advantage of FGF/FGFR signaling pathway in cells to cause uncontrolled growth leading to tumors.

While the FGFR genetic abnormalities may vary in frequency depending on the group of tumor types tested, there are clearly some patterns emerging in terms of which tumor types are likely to have specific kinds of genetic alterations in FGFR 1, 2, 3 or 4. Genetic alterations in the FGFR receptors can include point mutations, insertions/deletions, gene amplification, or translocations. The sensitivity of various gene alterations to FGFR inhibition is currently under investigation. Drugs targeting the FGF/FGFR pathway include small molecule tyrosine kinases inhibitors and ligand traps.

Several pharmaceutical companies have developed drugs that target and inhibit FGFR in tumors. Some of these are designed to target multiple members of the FGFR family. At MGH and other major cancer centers, clinical trials are available to patients whose tumors have been tested and found to have genetically altered FGFR. Treatment for these patients can be available on clinical studies testing these FGFR inhibitors, including FGFR inhibitors called TAS120 and Debio 1347. Other agents such as FGF401 and BLU554 are specific for inhibiting FGFR4 and are being tested in liver cancer. Contact the MGH Cancer Center to find out more about having genetic testing performed on a tumor, or for more information about these clinical trials.

Fibroblast growth factors (FGF’s) are ligands that bind to FGF cell surface receptors (FGFR’s) and activate them. Once activated, FGFR’s on normal cells transmit a growth signal inside the cell. This growth signal is transmitted via two important pathways inside cells; the RAS-dependent MAP kinase pathway, and a second signal pathway that involves PI3K and AKT. There are four different FGFR’s that make up a family of FGFR tyrosine kinase cell surface receptors, each having an extracellular domain that binds FGF ligands, a second domain that goes through the cell outer membrane, and a third domain that is inside the cell cytoplasm (see diagram above). FGFR signaling in normal cells stimulates proliferation, differentiation, embryonic development, cell migration, survival, angiogenesis (vascularization), and organogenesis (organ development).

Recently, FGFR genetic abnormalities have been found in several types of cancer. There are four FGFR family members, FGFR1, FGFR2, FGFR3, and FGFR4. Alterations in FGFR genes result in dysregulated FGF receptors and can promote cancer growth and metastasis. In a recent study of almost 5000 tumors, alterations in FGFR were found in 7% of of tumors. Among these tumors, alterations were identified in all 4 FGFR’s including FGFR1 (49%), FGFR2 (19%), FGFR3 (23%), and FGFR4 (7%). A small number of the tumors had genetic alterations in more than one type of FGFR. Clearly cancers have found a way to take advantage of FGF/FGFR signaling pathway in cells to cause uncontrolled growth leading to tumors.

While the FGFR genetic abnormalities may vary in frequency depending on the group of tumor types tested, there are clearly some patterns emerging in terms of which tumor types are likely to have specific kinds of genetic alterations in FGFR 1, 2, 3 or 4. Genetic alterations in the FGFR receptors can include point mutations, insertions/deletions, gene amplification, or translocations. The sensitivity of various gene alterations to FGFR inhibition is currently under investigation. Drugs targeting the FGF/FGFR pathway include small molecule tyrosine kinases inhibitors and ligand traps.

Several pharmaceutical companies have developed drugs that target and inhibit FGFR in tumors. Some of these are designed to target multiple members of the FGFR family. At MGH and other major cancer centers, clinical trials are available to patients whose tumors have been tested and found to have genetically altered FGFR. Treatment for these patients can be available on clinical studies testing these FGFR inhibitors, including FGFR inhibitors called TAS120 and Debio 1347. Other agents such as FGF401 and BLU554 are specific for inhibiting FGFR4 and are being tested in liver cancer. Contact the MGH Cancer Center to find out more about having genetic testing performed on a tumor, or for more information about these clinical trials.

PubMed ID's
9212826, 24265351
Expand Collapse FGFR 1, 2, 3 and 4  in Breast Cancer
Genetic alterations have been found with varying frequency in breast cancers. FGFR1 gene amplification, or alteration by genetic mutation have been identified in some breast cancers. FGFR2 gene amplifications and translocations have been found in some types of breast cancer.

There is also a germline (inherited) genetic alteration in FGFR2 that leads to an increased incidence of breast cancer.

Testing for these genetic alteration in tumors can be done at the MGH cancer center, or other major centers.



Genetic alterations have been found with varying frequency in breast cancers. FGFR1 gene amplification, or alteration by genetic mutation have been identified in some breast cancers. FGFR2 gene amplifications and translocations have been found in some types of breast cancer.

There is also a germline (inherited) genetic alteration in FGFR2 that leads to an increased incidence of breast cancer.

Testing for these genetic alteration in tumors can be done at the MGH cancer center, or other major centers.





PubMed ID's
9212826, 2426531
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 Results: 1-10 of 36 Per Page:
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Protocol # Title Location Status Match
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 DG
NCT03822312 A Pilot Study of Tomographic Optical Breast Imaging (DBT-TOBI) to Monitor Response to Neoadjuvant Therapy A Pilot Study of Tomographic Optical Breast Imaging (DBT-TOBI) to Monitor Response to Neoadjuvant Therapy MGH Open D
NCT02099058 A Study Evaluating the Safety, Pharmacokinetics (PK), and Preliminary Efficacy of ABBV-399 in Participants With Advanced Solid Tumors A Study Evaluating the Safety, Pharmacokinetics (PK), and Preliminary Efficacy of ABBV-399 in Participants With Advanced Solid Tumors MGH Open D
NCT03332797 A Study of GDC-9545 Alone or in Combination With Palbociclib and/or Luteinizing Hormone-Releasing Hormone (LHRH) Agonist in Locally Advanced or Metastatic Estrogen Receptor-Positive Breast Cancer A Study of GDC-9545 Alone or in Combination With Palbociclib and/or Luteinizing Hormone-Releasing Hormone (LHRH) Agonist in Locally Advanced or Metastatic Estrogen Receptor-Positive Breast Cancer MGH Open D
NCT02890069 A Study of PDR001 in Combination With LCL161, Everolimus or Panobinostat A Study of PDR001 in Combination With LCL161, Everolimus or Panobinostat MGH Open D
NCT03289962 A Study of RO7198457 as a Single Agent and in Combination With Atezolizumab in Participants With Locally Advanced or Metastatic Tumors A Study of RO7198457 as a Single Agent and in Combination With Atezolizumab in Participants With Locally Advanced or Metastatic Tumors MGH Open D
NCT03215511 A Study to Test the Safety of the Investigational Drug Selitrectinib in Children and Adults That May Treat Cancer A Study to Test the Safety of the Investigational Drug Selitrectinib in Children and Adults That May Treat Cancer MGH Open D
NCT03701334 A Trial to Evaluate Efficacy and Safety of Ribociclib With Endocrine Therapy as Adjuvant Treatment in Patients With HR+/HER2- Early Breast Cancer A Trial to Evaluate Efficacy and Safety of Ribociclib With Endocrine Therapy as Adjuvant Treatment in Patients With HR+/HER2- Early Breast Cancer 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
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
Trial Status: Showing Results: 1-10 of 36 Per Page:
1234Next »
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