Breast Cancer, BRCA1 and BRCA2, Inherited Germline Mutations

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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 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. (See DNA repair details if you select ATR from the drop down of genes on this site).

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 also 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. (See DNA repair proteins that have been found to be mutated in cancers in the graphic after selecting ATR on the drop down menu on this site).

Testing is available for BRCA1 and BRCA2 mutations (as well as the genes encoding many other proteins involved in DNA repair) at MGH, where there are established treatments such as PARP inhibitors in use, as well as clinical trials testing the newest therapies for improved treatment of 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. (See DNA repair details if you select ATR from the drop down of genes on this site).

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 also 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. (See DNA repair proteins that have been found to be mutated in cancers in the graphic after selecting ATR on the drop down menu on this site).

Testing is available for BRCA1 and BRCA2 mutations (as well as the genes encoding many other proteins involved in DNA repair) at MGH, where there are established treatments such as PARP inhibitors in use, as well as clinical trials testing the newest therapies for improved treatment of 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 Inherited Germline Mutations  in BRCA1 and BRCA2
In familial cancer syndromes, BRCA1 or BRCA2 are often lost or impaired in their function. These genetic alterations in the germline are inherited. The loss or inactivation of BRCA1 or BRCA2 genes have a serious impact on the cells ability to repair DNA damage when it occurs. (for more thorough information on DNA repair and the proteins involved, select the gene ATR on the drop down menu on this site). The accumulation of breaks in the DNA- or other types of damage-lead to the development of cancer.
In familial cancer syndromes, BRCA1 or BRCA2 are often lost or impaired in their function. These genetic alterations in the germline are inherited. The loss or inactivation of BRCA1 or BRCA2 genes have a serious impact on the cells ability to repair DNA damage when it occurs. (for more thorough information on DNA repair and the proteins involved, select the gene ATR on the drop down menu on this site). The accumulation of breaks in the DNA- or other types of damage-lead to the development of cancer.

Genetic alterations can be found in breast cancers in both the BRCA1 or BRCA2 genes. The loss or inactivation of BRCA1 or BRCA2 genes have a serious impact on the cells ability to repair DNA damage when it occurs (see more thorough information on DNA repair by selecting the ATR gene on the dropdown menu on this site). In familial cancer syndromes, BRCA1 or BRCA2 genes are lost or impaired in the germline, meaning the defect in the gene is inherited. Inherited BRCA1 or BRCA2 impairment causes an increased risk of developing cancer. Sporadic mutations (non-inherited) also occur in individuals, conferring the same increased risk of developing certain cancers.

Genetic alterations can be found in breast cancers in both the BRCA1 or BRCA2 genes. The loss or inactivation of BRCA1 or BRCA2 genes have a serious impact on the cells ability to repair DNA damage when it occurs (see more thorough information on DNA repair by selecting the ATR gene on the dropdown menu on this site). In familial cancer syndromes, BRCA1 or BRCA2 genes are lost or impaired in the germline, meaning the defect in the gene is inherited. Inherited BRCA1 or BRCA2 impairment causes an increased risk of developing cancer. Sporadic mutations (non-inherited) also occur in individuals, conferring the same increased risk of developing certain cancers.

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Your Matched Clinical Trials

Trial Matches: (D) - Disease, (G) - Gene, (M) - Mutation
Trial Status: Showing Results: 1-10 of 55 Per Page:
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Protocol # Title Location Status Match
NCT03329937 Study Evaluating the Antitumor Activity and Safety of Niraparib as Neoadjuvant Treatment Study Evaluating the Antitumor Activity and Safety of Niraparib as Neoadjuvant Treatment 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
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
NCT03134638 A Phase 1 Study of SY-1365 in Adult Patients With Advanced Solid Tumors A Phase 1 Study of SY-1365 in Adult Patients With Advanced Solid Tumors MGH Open D
NCT03088527 A Phase 1, First-in-Human Study of RAD140 in Postmenopausal Women With Hormone Receptor Positive Breast Cancer A Phase 1, First-in-Human Study of RAD140 in Postmenopausal Women With Hormone Receptor Positive Breast Cancer MGH Open D
NCT02979899 A RANDOMIZED PHASE 3 TRIAL OF TRC105 AND PAZOPANIB VERSUS PAZOPANIB ALONE IN PATIENTS WITH ADVANCED ANGIOSARCOMA A RANDOMIZED PHASE 3 TRIAL OF TRC105 AND PAZOPANIB VERSUS PAZOPANIB ALONE IN PATIENTS WITH ADVANCED ANGIOSARCOMA MGH Open D
NCT03051659 A Randomized Phase II Study Of Eribulin Mesylate With or Without Pembrolizumab For Metastatic Hormone Receptor Positive Breast Cancer A Randomized Phase II Study Of Eribulin Mesylate With or Without Pembrolizumab For Metastatic Hormone Receptor Positive Breast Cancer MGH Open D
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
NCT03148418 A Study in Participants Previously Enrolled in a Genentech− and/or F. Hoffmann-La Roche Ltd-Sponsored Atezolizumab Study (IMbrella A) A Study in Participants Previously Enrolled in a Genentech− and/or F. Hoffmann-La Roche Ltd-Sponsored Atezolizumab Study (IMbrella A) 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
Trial Status: Showing Results: 1-10 of 55 Per Page:
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