Breast Cancer, BRAF, G466A (c.1397G>C)

View:
Expand Collapse Breast Cancer  - General Description Breast cancer is a malignant tumor that usually forms in the glands that make milk (lobules) and the tubes (ducts) that carry milk to the nipple. This year about 231,8400 women (and 2,000 men) in the U.S. will be told by a doctor that they have breast cancer. Half of these people will be at least 61 years old. However, more than 10 times as many women, about 2.7 million, remain alive today after having been diagnosed with breast cancer.

Breast cancer is not one disease and is currently classified into 3 subtypes based on the receptors present on the surface of the cancer cell. If the tumor is positive for estrogen and/or progesterone receptors, it is called "hormone receptor breast cancer". In that case, drugs that block the hormones, such as tamoxifen or aromatase inhibitors, might work best initially. If the tumor is positive for another type of receptor, called HER2 (or ERBB2), it is called "HER2 positive breast cancer", and certain targeted therapies that block HER2, such as the medications trastuzumab (Herceptin), pertuzumab (perjeta), T-DM1 (Kadcyla), and lapatanib (Tykerb) might work best and are recommended by the FDA. If the tumor is negative for HER2, estrogen, and progesterone receptors, it is called "triple negative breast cancer".

Over time, breast cancer (and other tumors) can spread from the site where it started (the primary tumor) in 3 ways. First, breast cancer cells can invade the normal tissue surrounding the tumor. Second, breast cancer cells can enter the lymph system and travel through lymph vessels to distant parts of the body. Third, the breast cancer cells can get into the blood stream and travel to other places in the body. In these distant places, the breast cancer cells cause secondary (metastatic) tumors to grow. The main sites where breast cancer spreads are the lungs, liver and bones. There is a lot of ongoing research to identify other receptors and mutations that are actionable through treatment using appropriate new targeted therapies that could be developed against the cancer.

Source: National Cancer Institute, 2015
Breast cancer is the most common non-cutaneous cancer among women in the United States. This year about 231,840 women (and 2,000 men) in the U.S. will be told by a doctor that they have breast cancer. Half of these people will be at least 61 years old. However, more than 10 times as many women, about 2.7 million, remain alive today after having been diagnosed with breast cancer.

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, 2014
Breast cancer is a malignant tumor that usually forms in the glands that make milk (lobules) and the tubes (ducts) that carry milk to the nipple. This year about 231,8400 women (and 2,000 men) in the U.S. will be told by a doctor that they have breast cancer. Half of these people will be at least 61 years old. However, more than 10 times as many women, about 2.7 million, remain alive today after having been diagnosed with breast cancer.

Breast cancer is not one disease and is currently classified into 3 subtypes based on the receptors present on the surface of the cancer cell. If the tumor is positive for estrogen and/or progesterone receptors, it is called "hormone receptor breast cancer". In that case, drugs that block the hormones, such as tamoxifen or aromatase inhibitors, might work best initially. If the tumor is positive for another type of receptor, called HER2 (or ERBB2), it is called "HER2 positive breast cancer", and certain targeted therapies that block HER2, such as the medications trastuzumab (Herceptin), pertuzumab (perjeta), T-DM1 (Kadcyla), and lapatanib (Tykerb) might work best and are recommended by the FDA. If the tumor is negative for HER2, estrogen, and progesterone receptors, it is called "triple negative breast cancer".

Over time, breast cancer (and other tumors) can spread from the site where it started (the primary tumor) in 3 ways. First, breast cancer cells can invade the normal tissue surrounding the tumor. Second, breast cancer cells can enter the lymph system and travel through lymph vessels to distant parts of the body. Third, the breast cancer cells can get into the blood stream and travel to other places in the body. In these distant places, the breast cancer cells cause secondary (metastatic) tumors to grow. The main sites where breast cancer spreads are the lungs, liver and bones. There is a lot of ongoing research to identify other receptors and mutations that are actionable through treatment using appropriate new targeted therapies that could be developed against the cancer.

Source: National Cancer Institute, 2015
Breast cancer is the most common non-cutaneous cancer among women in the United States. This year about 231,840 women (and 2,000 men) in the U.S. will be told by a doctor that they have breast cancer. Half of these people will be at least 61 years old. However, more than 10 times as many women, about 2.7 million, remain alive today after having been diagnosed with breast cancer.

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, 2014
Expand Collapse BRAF  - General Description
CLICK IMAGE FOR MORE INFORMATION
The BRAF gene encodes for a serine/threonine kinase that activates the growth-promoting MAP kinase signaling cascade. BRAF is commonly activated by somatic point mutations in human cancers, most frequently by mutations located within the kinase domain at amino acid positions G466, G469, L597 and V600.

In regards to treatment, the Food and Drug Administration (FDA) approved vemurafenib for the treatment of unresectable or metastatic melanoma patients harboring specifically the BRAF V600E mutation, as detected by an FDA-approved test. In addition, there are a growing number of targeted agents that are being evaluated for the treatment of various BRAF-mutant advanced cancers, including other RAF kinase inhibitors and/or MEK inhibitors. Recently, the combination of the BRAF inhibitor dabrafenib with the MEK inhibitor trametinib was approved by FDA for the treatment of patients with BRAF V600E or V600K mutations.

Tumor mutation profiling performed clinically at the MGH Cancer Center has identified the highest incidence of BRAF mutations in thyroid cancer (30-40%), melanoma (20-30%) and colon cancer (10-15%).

Source: Genetics Home Reference
The BRAF gene encodes for a serine/threonine kinase that activates the growth-promoting MAP kinase signaling cascade. BRAF is commonly activated by somatic point mutations in human cancers, most frequently by mutations located within the kinase domain at amino acid positions G466, G469, L597 and V600.

In regards to treatment, the Food and Drug Administration (FDA) approved vemurafenib for the treatment of unresectable or metastatic melanoma patients harboring specifically the BRAF V600E mutation, as detected by an FDA-approved test. In addition, there are a growing number of targeted agents that are being evaluated for the treatment of various BRAF-mutant advanced cancers, including other RAF kinase inhibitors and/or MEK inhibitors. Recently, the combination of the BRAF inhibitor dabrafenib with the MEK inhibitor trametinib was approved by FDA for the treatment of patients with BRAF V600E or V600K mutations.

Tumor mutation profiling performed clinically at the MGH Cancer Center has identified the highest incidence of BRAF mutations in thyroid cancer (30-40%), melanoma (20-30%) and colon cancer (10-15%).

Source: Genetics Home Reference
PubMed ID's
12068308, 15947100, 20401974, 20425073, 21606968
Expand Collapse G466A (c.1397G>C)  in BRAF
The BRAF G466A mutation arises from a single nucleotide change (c.1397G>C) and results in an amino acid substitution of the glycine (G) at position 466 by an alanine (A).
The BRAF G466A mutation arises from a single nucleotide change (c.1397G>C) and results in an amino acid substitution of the glycine (G) at position 466 by an alanine (A).

BRAF mutations are rare in breast cancer. The prognostic and therapeutic significance of BRAF mutations in breast tumors are currently being evaluated. The presence of certain BRAF mutations to guide the use of BRAF inhibitors, such as vemurafenib, has so far only been approved for the treatment of melanoma (a type of skin cancer). It has not been established whether BRAF-mutant breast carcinomas similarly respond to BRAF inhibitors. However, clinical trials evaluating BRAF and MEK inhibitors, either as a single-agent or in combinations, are currently recruiting patients across cancer types, including breast cancer patients.

BRAF mutations are rare in breast cancer. The prognostic and therapeutic significance of BRAF mutations in breast tumors are currently being evaluated. The presence of certain BRAF mutations to guide the use of BRAF inhibitors, such as vemurafenib, has so far only been approved for the treatment of melanoma (a type of skin cancer). It has not been established whether BRAF-mutant breast carcinomas similarly respond to BRAF inhibitors. However, clinical trials evaluating BRAF and MEK inhibitors, either as a single-agent or in combinations, are currently recruiting patients across cancer types, including breast cancer patients.

PubMed ID's
20818844
Our Breast Cancer Team

Share with your Physican

Print information for your Physician.

Print information

Your Matched Clinical Trials

Trial Matches: (D) - Disease, (G) - Gene, (M) - Mutation
Trial Status: Showing Results: 1-10 of 38 Per Page:
1234Next »
Protocol # Title Location Status Match
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
NCT01862081 A Dose-escalation Study to Assess the Safety, Tolerability, and Pharmacokinetics of GDC-0032 in Combination With Docetaxel or With Paclitaxel in Patients With HER2-negative Locally Recurrent or Metastatic Breast Cancer or Non-small Cell Lung Cancer A Dose-escalation Study to Assess the Safety, Tolerability, and Pharmacokinetics of GDC-0032 in Combination With Docetaxel or With Paclitaxel in Patients With HER2-negative Locally Recurrent or Metastatic Breast Cancer or Non-small Cell Lung Cancer 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
NCT02219724 A Phase I, Open-Label Study of MOXR0916 in Patients With Locally Advanced or Metastatic Solid Tumors A Phase I, Open-Label Study of MOXR0916 in Patients With Locally Advanced or Metastatic Solid Tumors MGH Open D
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 D
NCT02365662 A Study Evaluating Safety and Pharmacokinetics of ABBV-221 in Subjects With Advanced Solid Tumor Types Likely to Exhibit Elevated Levels of Epidermal Growth Factor Receptor A Study Evaluating Safety and Pharmacokinetics of ABBV-221 in Subjects With Advanced Solid Tumor Types Likely to Exhibit Elevated Levels of Epidermal Growth Factor Receptor 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
Trial Status: Showing Results: 1-10 of 38 Per Page:
1234Next »
Our Breast Cancer Team

Share with your Physican

Print information for your Physician.

Print information