Breast Cancer, PIK3CA, R88Q (c.263G>A)

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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 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 R88Q (c.263G>A)  in PIK3CA
The PIK3CA R88Q mutation arises from a single nucleotide change (c.263G>A) and results in an amino acid substitution of the arginine (R) at position 88 by a glutamine (Q).
The PIK3CA R88Q mutation arises from a single nucleotide change (c.263G>A) and results in an amino acid substitution of the arginine (R) at position 88 by a glutamine (Q).

PIK3CA mutations are most commonly found in hormone receptor positive breast cancer, followed by HER2 positive breast cancer, and si least often found in triple-negative cancer. PIK2CA mutations are generally associated with a more favorable prognosis in early-stage disease, such as hormone receptor positivity and lymph node negativity and better overall survival.

Mutant PIK3CA proteins have increased activity that has been associated with resistance to endocrine therapy and decreased response rates to trastuzumab (a HER2-targeted antibody) or lapatinib (an EGFR and HER2 inhibitor).

Preclinical studies have shown that PIK3CA-mutant and HER2-amplified breast cancers are more sensitive to PI3K pathway inhibitors, when given either as a single-agent or in combination with other targeted therapies. Multiple clinical trials are currently underway to validate this hypothesis.

PIK3CA mutations are most commonly found in hormone receptor positive breast cancer, followed by HER2 positive breast cancer, and si least often found in triple-negative cancer. PIK2CA mutations are generally associated with a more favorable prognosis in early-stage disease, such as hormone receptor positivity and lymph node negativity and better overall survival.

Mutant PIK3CA proteins have increased activity that has been associated with resistance to endocrine therapy and decreased response rates to trastuzumab (a HER2-targeted antibody) or lapatinib (an EGFR and HER2 inhibitor).

Preclinical studies have shown that PIK3CA-mutant and HER2-amplified breast cancers are more sensitive to PI3K pathway inhibitors, when given either as a single-agent or in combination with other targeted therapies. Multiple clinical trials are currently underway to validate this hypothesis.

PubMed ID's
18676830, 21135276, 20085938, 21135276, 23400000
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Your Matched Clinical Trials

Trial Matches: (D) - Disease, (G) - Gene, (M) - Mutation
Trial Status: Showing Results: 1-10 of 41 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 DGM
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 DGM
NCT01971515 First-in-Human Dose Escalation Trial in Subjects With Advanced Malignancies First-in-Human Dose Escalation Trial in Subjects With Advanced Malignancies MGH Open DGM
NCT01857193 Phase Ib Trial of LEE011 With Everolimus (RAD001) and Exemestane in the Treatment of Hormone Receptor Positive HER2 Negative Advanced Breast Cancer Phase Ib Trial of LEE011 With Everolimus (RAD001) and Exemestane in the Treatment of Hormone Receptor Positive HER2 Negative Advanced Breast Cancer MGH Open DGM
NCT01872260 Study of LEE011, BYL719 and Letrozole in Advanced ER+ Breast Cancer Study of LEE011, BYL719 and Letrozole in Advanced ER+ Breast Cancer MGH Open DGM
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
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
Trial Status: Showing Results: 1-10 of 41 Per Page:
12345Next »
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