Breast Cancer, BRCA1 and BRCA2

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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 BRCA1 and BRCA2  - General Description
BRCA1 and BRCA2 are genes that encode proteins that play an important role in DNA repair. DNA is damaged in organisms through various means-UV from the sunlight, and exposure to other substances that cause breaks or cross-links in the DNA. DNA breaks also occur when cells are dividing and chromosomes need to separate, especially in cells that will eventually have half the number of chromosomes-the egg and sperm-during a process called meiosis. When the proteins that are involved in DNA repair are mutated or missing, breaks in the DNA do not get repaired, resulting in an accumulation of DNA that is incorrectly arranged, which leads to cancer. For this reason, BRCA1 and BRCA2 are called tumor suppressor genes, because when they function correctly, they participate in repairing DNA and preventing cancers.

When both strands of the DNA helix are disrupted, a process called Double Stranded DNA Repair takes place through a process called Homologous Recombination. This process involves a complex-or group-of many different proteins, some that attach onto the broken ends of DNA and then recruit other proteins to the site that are able to repair double strand breaks (DSB's) in the DNA so that the genes they encode are correctly sequenced when the repair is complete. Along with the BRCA proteins, proteins called RAD50 and RAD51 are part of the complex of proteins involved in DNA repair. During the DNA repair process, BRCA2 recruits RAD51 into the complex that is responsible for DNA repair.

BRCA1 and BRCA2 are genes that were discovered in families that had a high incidence of breast cancer. In these families, the genetic alterations in BRCA1 or BRCA2 are present in the germ-line, which means they are inherited. Inherited germ-line mutations in BRCA1 or BRCA2 greatly increase the likelihood of developing cancer of the breast or ovary, as well as prostate cancer in men. BRCA1 has many functions in the cell. It is involved in transcription of genes, targeting proteins for degradation in the cell, cell cycle regulation, and homologous recombination to repair DNA. BRCA2 is involved in homologous recombination to repair DNA. When either BRCA gene is missing or inactivated, the result is hereditary breast and ovarian cancer (HBOC). BRCA2 mutations confer a 50-60% lifetime risk of breast cancer, a 30% lifetime risk of ovarian cancer, a 20 fold risk of prostate cancer, a tenfold risk of pancreatic cancer, and potentially increased frequency of other cancers as well.

Patients can also develop somatic mutations or deletions of the BRCA1 or BRCA2 gene during their lifetime, instead of inheriting these mutations. Spontaneous mutations in BRCA1 or BRCA2 in an individual are called sporadic mutations. As more patients with different tumor types are tested for BRCA1 and BRCA2, it is becoming evident that multiple tumor types can harbor BRCA1 or BRCA2 mutations or deletions of the gene. Mutations in other genes involved in DNA repair can also contribute to the development of tumors. Testing is available for BRCA1 and BRCA2 mutations at MGH, where there are established treatments such as PARP inhibitors in use, and clinical trials ongoing for improved treatments for patients carrying these mutations.

Sources:
The DNA Damage Response: Ten Years After, J. Wade Harper, Stephen J. Elledge, Molecular Cell, Vol.28, Issue 5, 2007, pages 739-745.

DNA repair targeted therapy: The past or future of cancer treatment? 2017
Science Direct article pii/S0163725816000322
BRCA1 and BRCA2 are genes that encode proteins that play an important role in DNA repair. DNA is damaged in organisms through various means-UV from the sunlight, and exposure to other substances that cause breaks or cross-links in the DNA. DNA breaks also occur when cells are dividing and chromosomes need to separate, especially in cells that will eventually have half the number of chromosomes-the egg and sperm-during a process called meiosis. When the proteins that are involved in DNA repair are mutated or missing, breaks in the DNA do not get repaired, resulting in an accumulation of DNA that is incorrectly arranged, which leads to cancer. For this reason, BRCA1 and BRCA2 are called tumor suppressor genes, because when they function correctly, they participate in repairing DNA and preventing cancers.

When both strands of the DNA helix are disrupted, a process called Double Stranded DNA Repair takes place through a process called Homologous Recombination. This process involves a complex-or group-of many different proteins, some that attach onto the broken ends of DNA and then recruit other proteins to the site that are able to repair double strand breaks (DSB's) in the DNA so that the genes they encode are correctly sequenced when the repair is complete. Along with the BRCA proteins, proteins called RAD50 and RAD51 are part of the complex of proteins involved in DNA repair. During the DNA repair process, BRCA2 recruits RAD51 into the complex that is responsible for DNA repair.

BRCA1 and BRCA2 are genes that were discovered in families that had a high incidence of breast cancer. In these families, the genetic alterations in BRCA1 or BRCA2 are present in the germ-line, which means they are inherited. Inherited germ-line mutations in BRCA1 or BRCA2 greatly increase the likelihood of developing cancer of the breast or ovary, as well as prostate cancer in men. BRCA1 has many functions in the cell. It is involved in transcription of genes, targeting proteins for degradation in the cell, cell cycle regulation, and homologous recombination to repair DNA. BRCA2 is involved in homologous recombination to repair DNA. When either BRCA gene is missing or inactivated, the result is hereditary breast and ovarian cancer (HBOC). BRCA2 mutations confer a 50-60% lifetime risk of breast cancer, a 30% lifetime risk of ovarian cancer, a 20 fold risk of prostate cancer, a tenfold risk of pancreatic cancer, and potentially increased frequency of other cancers as well.

Patients can also develop somatic mutations or deletions of the BRCA1 or BRCA2 gene during their lifetime, instead of inheriting these mutations. Spontaneous mutations in BRCA1 or BRCA2 in an individual are called sporadic mutations. As more patients with different tumor types are tested for BRCA1 and BRCA2, it is becoming evident that multiple tumor types can harbor BRCA1 or BRCA2 mutations or deletions of the gene. Mutations in other genes involved in DNA repair can also contribute to the development of tumors. Testing is available for BRCA1 and BRCA2 mutations at MGH, where there are established treatments such as PARP inhibitors in use, and clinical trials ongoing for improved treatments for patients carrying these mutations.

Sources:
The DNA Damage Response: Ten Years After, J. Wade Harper, Stephen J. Elledge, Molecular Cell, Vol.28, Issue 5, 2007, pages 739-745.

DNA repair targeted therapy: The past or future of cancer treatment? 2017
Science Direct article pii/S0163725816000322
PubMed ID's
19553641,
Expand Collapse BRCA1 and BRCA2  in Breast Cancer
New information on cancer, genes, and mutations is being discovered each day. Currently, researchers have not found any information on the gene and disease you have chosen. Please check back as new data may be available soon.
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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 42 Per Page:
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Protocol # Title Location Status Match
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 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
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
NCT02082210 A Study of LY2875358 in Combination With Ramucirumab (LY3009806) in Participants With Advanced Cancer A Study of LY2875358 in Combination With Ramucirumab (LY3009806) in Participants With Advanced Cancer MGH Open D
Trial Status: Showing Results: 1-10 of 42 Per Page:
12345Next »
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