Breast Cancer, PIK3CA

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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 PIK3CA  - General Description
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PIK3CA is a gene that provides the code for making one piece of the phosphatidylinositol 3-kinase (PI3K) protein, which is an enzyme that is part of an important signaling pathway (PI3K/AKT) involved in controlling the growth, division, survival, nutrient utilization, movement and structure of cells. PIK3CA encodes the catalytic subunit of PI3K, which is the part of the protein that lets it function as an enzyme. PI3K function is tightly maintained in normal cells. The enzymatic activity is activated by specific signals from growth factor receptor tyrosine kinases (RTKs) or from activated RAS proteins. PI3K then generates molecules that attract another enzyme (particularly AKT) to the cell membrane, where it is activated. The activated AKT acts on other proteins that regulate various cell processes that promotes cell growth and survival.

Mutations in PIK3CA lead to enhanced activation of its signaling function, thereby driving the tumorigenic process. These activating mutations are commonly associated with breast and colon cancer, and more rarely with melanoma of the skin. Defects in this gene have also been associated with ovarian cancer, endometrial cancer, and liver cancer.

Tumor mutation profiling performed clinically at the MGH Cancer Center has identified PIK3CA mutations across a broad-spectrum of cancer types. The highest incidence of PIK3CA mutations have been found in endometrial cancer (25%), breast cancer (20%), colon cancer (25%) and cancers of the head and neck (10%). In the other major tumor types, PIK3CA mutations have been found in less than 10% of cases that have been tested.

Sources: Genetics Home Reference
The PIK3CA gene encodes the p110 alpha catalytic subunit of the phosphoinositol 3-kinase (PI3K) complex. PI3K receives upstream activation signals from growth factor receptor tyrosine kinases (e.g. EGFR family members), and in turn signals through AKT and mTOR in order to promote cell survival, cell growth and cellular proliferation. PIK3CA mutations lead to increased activation of PI3K/AKT/mTOR signaling. PI3K function is opposed by PTEN, a lipid phosphatase that is often inactivated by mutations or silenced by methylation in many cancers.

Tumor mutation profiling performed clinically at the MGH Cancer Center has identified PIK3CA mutations across a broad-spectrum of cancer types. The highest incidence of PIK3CA mutations have been found in endometrial cancer (25%), breast cancer (20%), colon cancer (25%) and cancers of the head and neck (10%). In the other major tumor types, PIK3CA mutations have been found in less than 10% of cases that have been tested.

Sources: Genetics Home Reference
Expand Collapse PIK3CA  in Breast Cancer
Many breast cancers have genetically altered PIK3CA proteins. Breast cancer mutations in PIK3A invariably result in an altered form of the protein that is in a constant state of activation, and can no longer be regulated normally. There are many ongoing clinical trials with PIK3CA inhibitors, in combination with other targeted therapies as well as immune therapies.

Many breast cancers have genetically altered PIK3CA proteins. Breast cancer mutations in PIK3A invariably result in an altered form of the protein that is in a constant state of activation, and can no longer be regulated normally. There are many ongoing clinical trials with PIK3CA inhibitors, in combination with other targeted therapies as well as immune therapies.

PubMed ID's
18676830, 21135276, 20085938, 21135276, 23400000
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 42 Per Page:
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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 DG
NCT01791478 BYL719 and Letrozole in Post-Menopausal Patients With Hormone Receptor-Positive Metastatic Breast Cancer BYL719 and Letrozole in Post-Menopausal Patients With Hormone Receptor-Positive Metastatic Breast Cancer MGH Open DG
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
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
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 42 Per Page:
12345Next »
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