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Expand Collapse Gastric/Esophageal  - General Description Cancers of the stomach (gastric) and esophagus are a major public health concern. Other terms for these cancers include gastroesophageal cancer or esophagogastric cancer. About 13,000 men and 8,000 women will be diagnosed with gastric or esophageal cancer yearly in the United States. Though the incidence of certain types of gastric cancers has decreased, cancers of the gastroesophageal (GE) junction and lower esophagus are increasing in frequency.

The innermost layers of the esophagus and stomach are the site where esophageal and gastric cancers most often begin. Cancers affecting the esophagus are usually either “squamous cell carcinoma" (SCC) or “adenocarcinoma”, which differ in a number of ways. Most SCCs develop in the upper or middle esophageal region and smoking and alcohol use are the major risk factors. Adenocarcinomas of the esophagus tend to start in the distal esophagus or GE junction. For esophageal or GE junction adenocarcinomas, the predominant risk factors are obesity, smoking, having a disorder called “Barrett’s esophagus”, or gastroesophageal reflux disease (GERD). Cancer arising in the stomach is mainly adenocarcinoma. Infection in the stomach by a certain bacteria called Helicobacter pylori is a primary risk factor for developing this disease.

Stomach and esophageal cancers tend to develop slowly over many years. Precancerous changes that occur in the inner mucosal layer of the stomach or esophagus rarely cause symptoms, and therefore frequently go undetected. Once symptoms develop and the cancer has been identified, esophagogastric cancers can be removed using surgery as the primary method of treatment. However, when these cancers spread from the area where they initially develop (the “primary” tumor), the major focus of treatment becomes chemotherapy with or without radiation therapy. There are three different ways tumors can spread. First, the primary tumor can grow and invade the other layers of the stomach or esophagus and invade normal tissue surrounding the tumor. Second, cancer cells from the tumor can enter the lymph system and travel through lymph vessels to distant parts of the body. Third, cancer cells from the tumor can get into the bloodstream, and travel to other places in the body. In these distant places, the esophagogastric cancer cells can cause secondary tumors (metastases) to grow. To find out whether the cancer is limited to the primary site or whether the cancer has begun to spread, the lymph nodes near the primary tumor are often evaluated through biopsy. Several kinds of imaging may also be performed in diagnosing gastric and esophageal cancers to “stage” the disease. These include chest x-ray, MRI, CT scan, and PET scan techniques.

Testing for the presence of a specific cancer-related protein called HER2 (ERBB2) in the tumor specimen is an additional evaluation that is performed in esophagogastric cancer. The presence of HER2-expression in esophagogastric cancer has important therapeutic implications. There are also trials being conducted for patients with MET-amplified or EGFR-amplified tumors.

Sources: National Cancer Institute, 2013; The American Cancer Society, 2013; Partners Clinical Handbook, 2013
Cancers of the stomach and esophagus, also collectively referred to as gastroesophageal or esophagogastric cancer, represent a major public health concern. Gastric cancer is the fourth most commonly diagnosed cancer and the second most common cause of cancer death worldwide. Gastric cancer incidence varies throughout the world, with Japan and Korea having the highest incidences. According to the American Cancer Society (ACS), 21,600 new cases and 10,990 deaths are estimated for 2013 in the United States. For esophageal cancers, the ACS estimates 17,990 new esophageal cancers diagnosed in the United States during 2013, resulting in about 15,210 deaths (12,220 men and 2,990 women).

Most cancers involving the esophagus or stomach are either squamous cell (SCC) or adenocarcinoma. Squamous cell cancers were formerly the predominant histology for esophageal cancers. However, since the 1970s, the frequency of adenocarcinomas of the esophagus, gastroesophageal junction (GEJ), and gastric cardia has increased dramatically. Esophageal SCCs and adenocarcinomas of the distal esophagus, GEJ, or gastric cardia differ in a number of ways. Most SCCs develop in the “middle esophageal” region, and smoking and alcohol use are the major risk factors. For adenocarcinomas, the predominant risk factors are obesity, smoking, and “Barrett’s esophagus” with associated intestinal metaplasia, or gastroesophageal reflux disease (GERD). Meanwhile, risk factors associated with more distal gastric adenocarcinomas include 1) Helicobacter pylori infection, 2) a diet low in fruits and vegetables, 3) a diet high in salted, smoked, or preserved foods, 3) chronic atrophic gastritis, and 4) pernicious anemia, among other risk factors.

Gastric and esophageal cancers tend to develop slowly over many years in the inner mucosal layer of the stomach or esophagus. These early changes rarely cause symptoms, and therefore frequently go undetected. As esophageal and gastric cancers become more advanced, symptoms can include discomfort or pain in the stomach area, difficulty swallowing, nausea and vomiting, weight loss, feeling full or bloated after a small meal, vomiting blood, or having blood in the stool. Once symptoms bring a patient to medical attention, endoscopic biopsy is routinely used to diagnose the cancer. Staging workup should include radiographic imaging, such as CT with intravenous contrast, with or without accompanying PET scan. In the case of esophageal cancer, endoscopic ultrasound (EUS) with fine-needle biopsy of suspicious lymph nodes may be used to more accurately stage locoregional disease. The staging workup of gastric cancers may involve diagnostic laparoscopy to rule out occult metastatic disease.

Treatment options for esophageal and gastric cancers depend on the size and location of the tumor, the stage of disease, and overall health of the patient. In the absence of distant spread of disease, a multi-disciplinary approach involving surgery, radiation and chemotherapy is required. Except in cases of very early-stage disease, neoadjuvant and peri-operative approaches involving chemotherapy with or without radiation should be considered in order to optimize the chances of curative resection. In cases of gastric or GEJ cancers where surgery is pursued first, adjuvant therapy may be appropriate.

Metastatic esophageal and gastric adenocarcinomas are treated similarly with systemic chemotherapy. Despite a variety of chemotherapeutic regimens that are available, the median survival for metastatic esophagogastric cancer patients is less than 1 year. Therefore, there has been a growing interest in the molecular features of these diseases, with the expectation that activating molecular lesions may be targets for novel therapeutic agents. For patients with HER2-positive tumors, targeted therapy is now an option. There are also trials being conducted for patients with MET-amplified or EGFR-amplified tumors.

Source: National Cancer Institute, 2013; The American Cancer Society, 2013; Up-To-Date, 2013
Cancers of the stomach (gastric) and esophagus are a major public health concern. Other terms for these cancers include gastroesophageal cancer or esophagogastric cancer. About 13,000 men and 8,000 women will be diagnosed with gastric or esophageal cancer yearly in the United States. Though the incidence of certain types of gastric cancers has decreased, cancers of the gastroesophageal (GE) junction and lower esophagus are increasing in frequency.

The innermost layers of the esophagus and stomach are the site where esophageal and gastric cancers most often begin. Cancers affecting the esophagus are usually either “squamous cell carcinoma" (SCC) or “adenocarcinoma”, which differ in a number of ways. Most SCCs develop in the upper or middle esophageal region and smoking and alcohol use are the major risk factors. Adenocarcinomas of the esophagus tend to start in the distal esophagus or GE junction. For esophageal or GE junction adenocarcinomas, the predominant risk factors are obesity, smoking, having a disorder called “Barrett’s esophagus”, or gastroesophageal reflux disease (GERD). Cancer arising in the stomach is mainly adenocarcinoma. Infection in the stomach by a certain bacteria called Helicobacter pylori is a primary risk factor for developing this disease.

Stomach and esophageal cancers tend to develop slowly over many years. Precancerous changes that occur in the inner mucosal layer of the stomach or esophagus rarely cause symptoms, and therefore frequently go undetected. Once symptoms develop and the cancer has been identified, esophagogastric cancers can be removed using surgery as the primary method of treatment. However, when these cancers spread from the area where they initially develop (the “primary” tumor), the major focus of treatment becomes chemotherapy with or without radiation therapy. There are three different ways tumors can spread. First, the primary tumor can grow and invade the other layers of the stomach or esophagus and invade normal tissue surrounding the tumor. Second, cancer cells from the tumor can enter the lymph system and travel through lymph vessels to distant parts of the body. Third, cancer cells from the tumor can get into the bloodstream, and travel to other places in the body. In these distant places, the esophagogastric cancer cells can cause secondary tumors (metastases) to grow. To find out whether the cancer is limited to the primary site or whether the cancer has begun to spread, the lymph nodes near the primary tumor are often evaluated through biopsy. Several kinds of imaging may also be performed in diagnosing gastric and esophageal cancers to “stage” the disease. These include chest x-ray, MRI, CT scan, and PET scan techniques.

Testing for the presence of a specific cancer-related protein called HER2 (ERBB2) in the tumor specimen is an additional evaluation that is performed in esophagogastric cancer. The presence of HER2-expression in esophagogastric cancer has important therapeutic implications. There are also trials being conducted for patients with MET-amplified or EGFR-amplified tumors.

Sources: National Cancer Institute, 2013; The American Cancer Society, 2013; Partners Clinical Handbook, 2013
Cancers of the stomach and esophagus, also collectively referred to as gastroesophageal or esophagogastric cancer, represent a major public health concern. Gastric cancer is the fourth most commonly diagnosed cancer and the second most common cause of cancer death worldwide. Gastric cancer incidence varies throughout the world, with Japan and Korea having the highest incidences. According to the American Cancer Society (ACS), 21,600 new cases and 10,990 deaths are estimated for 2013 in the United States. For esophageal cancers, the ACS estimates 17,990 new esophageal cancers diagnosed in the United States during 2013, resulting in about 15,210 deaths (12,220 men and 2,990 women).

Most cancers involving the esophagus or stomach are either squamous cell (SCC) or adenocarcinoma. Squamous cell cancers were formerly the predominant histology for esophageal cancers. However, since the 1970s, the frequency of adenocarcinomas of the esophagus, gastroesophageal junction (GEJ), and gastric cardia has increased dramatically. Esophageal SCCs and adenocarcinomas of the distal esophagus, GEJ, or gastric cardia differ in a number of ways. Most SCCs develop in the “middle esophageal” region, and smoking and alcohol use are the major risk factors. For adenocarcinomas, the predominant risk factors are obesity, smoking, and “Barrett’s esophagus” with associated intestinal metaplasia, or gastroesophageal reflux disease (GERD). Meanwhile, risk factors associated with more distal gastric adenocarcinomas include 1) Helicobacter pylori infection, 2) a diet low in fruits and vegetables, 3) a diet high in salted, smoked, or preserved foods, 3) chronic atrophic gastritis, and 4) pernicious anemia, among other risk factors.

Gastric and esophageal cancers tend to develop slowly over many years in the inner mucosal layer of the stomach or esophagus. These early changes rarely cause symptoms, and therefore frequently go undetected. As esophageal and gastric cancers become more advanced, symptoms can include discomfort or pain in the stomach area, difficulty swallowing, nausea and vomiting, weight loss, feeling full or bloated after a small meal, vomiting blood, or having blood in the stool. Once symptoms bring a patient to medical attention, endoscopic biopsy is routinely used to diagnose the cancer. Staging workup should include radiographic imaging, such as CT with intravenous contrast, with or without accompanying PET scan. In the case of esophageal cancer, endoscopic ultrasound (EUS) with fine-needle biopsy of suspicious lymph nodes may be used to more accurately stage locoregional disease. The staging workup of gastric cancers may involve diagnostic laparoscopy to rule out occult metastatic disease.

Treatment options for esophageal and gastric cancers depend on the size and location of the tumor, the stage of disease, and overall health of the patient. In the absence of distant spread of disease, a multi-disciplinary approach involving surgery, radiation and chemotherapy is required. Except in cases of very early-stage disease, neoadjuvant and peri-operative approaches involving chemotherapy with or without radiation should be considered in order to optimize the chances of curative resection. In cases of gastric or GEJ cancers where surgery is pursued first, adjuvant therapy may be appropriate.

Metastatic esophageal and gastric adenocarcinomas are treated similarly with systemic chemotherapy. Despite a variety of chemotherapeutic regimens that are available, the median survival for metastatic esophagogastric cancer patients is less than 1 year. Therefore, there has been a growing interest in the molecular features of these diseases, with the expectation that activating molecular lesions may be targets for novel therapeutic agents. For patients with HER2-positive tumors, targeted therapy is now an option. There are also trials being conducted for patients with MET-amplified or EGFR-amplified tumors.

Source: National Cancer Institute, 2013; The American Cancer Society, 2013; Up-To-Date, 2013
Expand Collapse ERBB2 (HER2)  - General Description
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ERBB2, often called HER2, is a gene that provides the code for making a cell surface protein called the ErbB2 (HER2) growth factor receptor. When certain growth factors (proteins that stimulate cell growth and division) bind to this receptor, they activate a signaling system inside the cell that ultimately promotes diverse functions such as growth, interaction and adhesion between cells, and ability of the cell to migrate within tissues. In some tumors, the activation of HER2 signaling is an important mechanism that drives the disease process. This can occur through HER2 gene amplification (the most common mechanism) or HER2 gene mutation in the cancer cells.

Extra copies of the HER2 gene (gene amplification) have been found in a number of different cancers. This causes the cancer cells to make excess HER2 (overexpression), which in turn, tells the cells to grow and divide in an uncontrolled manner. The presence of amplified HER2 has been reported in approximately 25% of breast tumors, 20% of esophageal tumors, 15% of gastric cancers and 20% of certain ovarian tumors. The FDA has approved the targeted therapies including trastuzumab (Herceptin), pertuzumab (Perjeta), lapatinib (Tykerb), and T-DM1 (Kadcyla) for the treatment of patients with certain kinds of breast cancer in which HER2 is overexpressed. Trastuzumab is also FDA approved to treat gastric cancer with amplification of this receptor.

Mutations in HER2 involving small duplications of the gene can promote resistance to some EGFR targeted therapies, but on the other hand, promote response to certain HER2 inhibitors. While very rare, these mutations are most often associated with non-small cell lung cancer, but have also been described in other malignancies including brain, gastric, breast and ovarian tumors. Tumor mutation profiling performed clinically at the MGH Cancer Center has identified HER2 mutations in a small subset of non-HER2 amplified breast cancer (1%) and non-small cell lung cancers (1%).

Source: Genetics Home Reference
The ERBB2 gene encodes for a cell surface protein that belongs to the ERBB family of receptor tyrosine kinases, known as ErbB2 (more commonly referred to as HER2). Four members of the ERBB family have been identified; EGFR (ERBB1, HER1), ERBB2 (HER2), ERBB3 (HER3) and ERBB4 (HER4). Binding of a ligand induces ERBB receptor homo-/hetero-dimerization and triggers a signaling cascade that drives many cellular responses. These include the activation of PI3K/AKT/mTOR and MAP kinase/ERK pathways, which promote cell survival and proliferation. Although there is no known ligand for HER2, HER2 is the preferred dimerization partner for the other ERBB receptors. In some cancers, HER2 activity is increased through protein overexpression or gene mutation.

The overexpression of HER2 is tightly associated with amplification of the HER2 gene. HER2 amplification has been reported in multiple malignancies, including breast cancer (25% incidence), esophageal cancer (20% incidence), gastric cancer (15% incidence), and mucinous ovarian carcinomas (20% incidence).

Mutations in HER2 have also been identified as an important mechanism that could drive tumor growth and confer resistance to targeted therapies. In-frame duplication/insertions in a region of HER2 exon 20 that is conserved with EGFR have been demonstrated in ~2% of lung cancer patients. Mutations in HER2 receptor have also been described in a small subset of non-HER2 amplified breast cancer (1%).

Source: Genetics Home Reference
PubMed ID's
15864276, 9130710, 15457249, 16397024, 18772890, 16843263, 16988931, 22899400
Expand Collapse ERBB2 (HER2)  in Gastric/Esophageal
HER2 gene amplification, when detected in the tumor tissue, is currently used as a marker to direct the FDA-approved use of trastuzumab (Herceptin) in combination with cisplatin and a fluoropyrimidine (chemotherapy drugs) for the first-line treatment of patients with metastatic gastric or gastroesophageal junction cancer. Additional HER2 targeted drugs are also being evaluated in clinical trial studies, which include testing in patients with esophageal cancer as well as patients with gastric cancer who are resistant to trastuzumab treatment.

Tumor profiling performed at the MGH Cancer Center has identified HER2 gene amplification in approximately 20% of esophageal cancers and 15% of gastric cancers.

HER2 gene amplification, when detected in the tumor tissue, is currently used as a marker to direct the FDA-approved use of trastuzumab (Herceptin) in combination with cisplatin and a fluoropyrimidine (chemotherapy drugs) for the first-line treatment of patients with metastatic gastric or gastroesophageal junction cancer. Additional HER2 targeted drugs are also being evaluated in clinical trial studies, which include testing in patients with esophageal cancer as well as patients with gastric cancer who are resistant to trastuzumab treatment.

Tumor profiling performed at the MGH Cancer Center has identified HER2 gene amplification in approximately 20% of esophageal cancers and 15% of gastric cancers.

PubMed ID's
20728210, 21421462, 15668283, 22143936, 22646280, 22751336, 20542421, 21335337, 21415234
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 17 Per Page:
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Protocol # Title Location Status Match
NCT01953926 An Open-label, Phase 2 Study of Neratinib in Patients With Solid Tumors With Somatic Human Epidermal Growth Factor Receptor (EGFR, HER2, HER3) Mutations or EGFR Gene Amplification An Open-label, Phase 2 Study of Neratinib in Patients With Solid Tumors With Somatic Human Epidermal Growth Factor Receptor (EGFR, HER2, HER3) Mutations or EGFR Gene Amplification MGH Open DG
NCT02500199 Phase 1, Dose Escalation Study of Pyrotinib in Patients Who Progressed on Prior HER2 Targeted Therapy Phase 1, Dose Escalation Study of Pyrotinib in Patients Who Progressed on Prior HER2 Targeted Therapy MGH Open DG
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
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
NCT02013154 A Study of DKN-01 in Combination With Paclitaxel A Study of DKN-01 in Combination With Paclitaxel MGH Open D
NCT02471846 A Study of GDC-0919 and Atezolizumab Combination Treatment in Participants With Locally Advanced or Metastatic Solid Tumors A Study of GDC-0919 and Atezolizumab Combination Treatment in Participants With Locally Advanced or Metastatic Solid Tumors 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
NCT02323191 A Study of RO5509554 and MPDL3280A Administered in Combination in Patients With Advanced Solid Tumors A Study of RO5509554 and MPDL3280A Administered in Combination in Patients With Advanced Solid Tumors MGH Open D
NCT02318329 Open-Label, Dose-Finding Study Evaluating Safety and PK of FPA144 in Patients With Advanced Solid Tumors Open-Label, Dose-Finding Study Evaluating Safety and PK of FPA144 in Patients With Advanced Solid Tumors MGH Open D
Trial Status: Showing Results: 1-10 of 17 Per Page:
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