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What's The Outlook For People With HER2-Positive Stage 4 Esophageal Cancer?
HER2-positive cancer cells produce HER2 protein that stimulates cell growth. Stage 4 HER2-positive esophageal cancer has a poor outlook, but some targeted therapy drugs may help people live longer.
According to estimates from the American Cancer Society (ACS), about 17,030 men and 4,530 women in the United States will receive a diagnosis of esophageal cancer in 2023. Roughly half of these people will have cancer spread to distant body parts when they've received a diagnosis.
Human epidermal growth factor receptor 2 (HER2) is a protein produced by some cancer cells. Cancer that tests positive for this protein is called HER2-positive esophageal cancer.
Stage 4 HER2-positive esophageal cancer means that cancer has spread extensively into the tissue around your food pipe (esophagus) or to distant body parts.
Stage 4 esophageal cancer is difficult to treat and has a poor outlook. It's often treated with a combination of chemotherapy and targeted therapy drugs such as trastuzumab (Herceptin).
Keep reading to learn more about the treatment and outlook for people with HER2-positive stage 4 esophageal cancer.
HER2 is a protein that promotes the growth and division of cells. HER2-positive cancer cells produce too much of this protein, which can cause them to grow quickly.
Knowing whether your cancer is HER2-positive helps doctors determine whether you may respond to some targeted therapy drugs. Targeted therapy drugs are like chemotherapy drugs, but they largely destroy cancer cells without damaging healthy cells.
Other types of HER2-positive cancers, such as breast and stomach cancers, may have a poorer outlook than HER2-negative cancers. But research suggests that HER2-positive esophageal cancer isn't linked with poorer survival rates.
How common is HER2-positive esophageal cancer?According to the National Cancer Institute, esophageal cancer makes up about 1% of cancers in the United States. About 4 out of 100,000 people develop esophageal cancer each year. Esophageal adenocarcinoma, a type of esophageal cancer, makes up about 80% of these cancers.
Roughly 17% of esophageal adenocarcinomas are HER2-positive.
The next most common type of esophageal cancer in the United States is esophageal squamous cell carcinoma.
In a 2021 study, researchers estimated that 8.6–10% of esophageal squamous cell carcinomas were HER2-positive among 1,505 people.
Doctors divide esophageal cancer into stages depending on how far it's spread. The most common staging system doctors use is the American Joint Committee on Cancer (AJCC)'s TNM system.
Learn more about esophageal cancer stages.
Stage 4 is the highest stage of esophageal cancer. It can be further broken into stage 4A and stage 4B:
Researchers have found that some targeted therapy drugs improve the survival of people with HER2-positive adenocarcinoma. These drugs include:
Trastuzumab (Herceptin) with chemotherapy is the standard first-line treatment for people with HER2-positive cancer spread to distant tissues.
In 2021, the FDA granted accelerated approval of another targeted therapy drug called pembrolizumab (Keytruda). This drug, in combination with trastuzumab and chemotherapy, is now approved to treat HER2-positive cancer that's not surgically treatable.
Fam-trastuzumab deruxtecan (Enhertu) is the second-line therapy. If you have HER2-positive cancer and your condition worsens while taking trastuzumab (Herceptin), your doctor may recommend fam-trastuzumab deruxtecan.
Healthcare professionals currently do not use targeted therapy to treat squamous cell esophageal cancer.
New targeted therapy and immunotherapy drugs are in various points of development for treating HER2 cancer.
People with esophageal cancer that has spread to distant tissues tend to have a poor outlook. ACS says that people with distant spread have a 5-year relative survival rate of about 6%. This means they live at least 5 years, but only about 6% as often as people without esophageal cancer.
Cancer contained in the esophagus or surrounding tissue is easier to treat and has a better outlook.
The American Cancer Society and National Cancer Institute don't use the AJCC's TNM staging system for reporting survival statistics. Instead, they divide the cancer into three categories depending on how far it has spread.
Here's a look at the relative survival rates of esophageal cancer in the United States for 2012–2018, as per ACS:
In a 2018 study, researchers found no significant difference in survival between people with HER2-positive or HER2-negative esophageal cancer.
Learn more about esophageal cancer survival rates.
HER2 is a protein produced by healthy cells and some cancer cells that stimulate cell growth. Knowing whether your cancer is HER2-positive helps doctors determine whether you may respond to certain targeted therapy drugs.
Stage 4 esophageal cancer tends to be very difficult to treat. Treatment often focuses on helping improve your overall survival time and lowering symptoms.
Signs And Symptoms Of Esophageal Cancer
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Medically reviewed by Benjamin Leach, MD
Esophageal cancer is a type of cancer that begins in the lining of the esophagus. The esophagus is a muscular tube that connects the throat to the stomach. When cancer develops, it usually occurs in the innermost layer of the esophagus and then spreads outward.
Esophageal cancer does not usually cause symptoms until the later stages. Possible symptoms include trouble swallowing, vomiting, and chest pain. It can also lead to unintended weight loss. Esophageal cancer makes up about 1% of all cancers in the United States.
Trouble SwallowingThe most common symptom of esophageal cancer is trouble swallowing (dysphagia). Unfortunately, symptoms like this do not start until the later stages of the disease. Esophageal cancer does not cause symptoms in the early stages.
As cancer cells grow and multiply in the esophagus, they form a mass of cells called a tumor. When the tumor grows, it can start to cause problems with eating and swallowing. At first, you may feel like food is getting stuck in your throat when you eat. You may notice yourself trying to compensate by taking smaller bites of food or sipping water after each bite.
As cancer progresses, it will get harder to swallow. In response to this, your body will start to produce more saliva to help food pass through the esophagus. You may notice an increase in the amount of spit or mucus in your mouth.
VomitingTrouble swallowing can lead to vomiting. When food becomes lodged in your esophagus, your body may vomit to remove it and prevent trouble breathing.
It is common for people with esophageal cancer to lose weight without trying to. This is because they end up eating less due to trouble swallowing. Vomiting after meals also contributes to weight loss. If you notice that you are vomiting when you try to eat, see your healthcare provider right away.
Chest PainMany people with esophageal cancer notice a sensation of pain or burning in their chests. This feeling is a common symptom of acid reflux, so many people ignore it. It is important to note that the majority of people with heartburn symptoms simply have heartburn and not cancer.
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Esophageal cancer causes chest pain when the tumor grows big enough to block food. As you eat, you may feel discomfort or pain as food tries to pass around the tumor. Esophageal cancer can also lead to a chronic cough or hoarseness.
BleedingEsophageal cancer can cause bleeding in the esophagus. When this happens, the blood travels through your digestive system and causes your stool to appear black.
Over time, bleeding can lead to a shortage of red blood cells (anemia). A common sign of anemia is daytime sleepiness or fatigue.
Symptoms in Men/WomenPeople assigned male at birth are much more likely to be diagnosed with esophageal cancer than those assigned female. This may be because men are typically more likely to use tobacco and alcohol, two risk factors for esophageal cancer.
When to See a Healthcare ProviderBecause esophageal cancer does not cause symptoms in the early stages, it is critical to see your healthcare provider as soon as you develop symptoms. Your provider may refer you to an oncologist, a medical doctor who specializes in the treatment of cancer, for testing and treatment.
See your provider if you develop any of the following symptoms:
It is especially important to get your symptoms checked out if you have any known risk factors for esophageal cancer, including:
Being assigned male at birth
Age over 55
Tobacco use
Frequent or excessive alcohol use
Gastroesophageal reflux disease (GERD)
Obesity
History of cancer
A diet rich in processed meats
History of a disease that affects the esophagus including Barrett's esophagus, achalasia, or tylosis
Human papillomvirus (HPV)
Esophageal cancer is a type of cancer that begins in the esophagus, the muscular tube that connects the throat to the stomach. Common symptoms include difficulty swallowing, vomiting, unintended weight loss, chest pain, heartburn, black stool, and fatigue.
Unfortunately, esophageal cancer does not usually cause symptoms until the later stages when it is more difficult to treat. See your healthcare provider as soon as you develop any signs or symptoms of esophageal cancer.
Frequently Asked QuestionsWhat are the red flags for esophageal cancer?
The most common red flags for esophageal cancer include difficulty swallowing, vomiting, unintended weight loss, chest pain, heartburn, black stool, and fatigue. This type of cancer does not tend to cause symptoms until the later stages.
Does esophageal cancer spread quickly?
Esophageal cancer usually develops and spreads without causing any signs or symptoms. Many people are diagnosed with esophageal in the later stages because that is when they first noticed any changes.
Where does esophageal cancer spread to first?
Esophageal cancer usually starts in the innermost layer of the esophagus and then grows out from there. Once it grows through the esophagus, this type of cancer usually spreads to the lymph nodes. It may also spread to nearby tissues including the tissue covering the lungs (the pleura), the sac around the heart (the pericardium), and the muscle below the lungs (the diaphragm).
What can be mistaken for esophageal cancer?
Esophageal cancer causes a burning sensation in the chest. This occurs when the tumor grows big enough to block food from passing through the esophagus. This burning sensation is often mistaken for acid reflux or heartburn.
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Identification Of Genetic Drivers For Esophageal Cancer Creates New Opportunity For Screening, Treatment
Esophageal adenocarcinoma (EAC) is a highly lethal cancer, with a five-year survival rate of less than 20%. Although a precursor lesion to EAC, called Barrett's esophagus (BE), is present in roughly 7% of middle-aged adults, less than 1% of BE patients will progress to EAC, making it difficult to determine which individuals are at risk of developing this deadly cancer.
To better understand why only a small fraction of individuals with BE develop EAC, investigators from the Mass General Cancer Center, a member of the Mass General Brigham health care system, used genomic databases to identify genetic drivers associated with EAC.
Their results, published in Gastroenterology, highlight that 9% of EAC patients harbor mutations in cancer-predisposing genes, shedding light on the causes of progression to the disease and new possibilities for screening and treatment.
"The development of EAC was previously thought of as a 'bad luck' phenomenon, so we were stunned to find cancer-predisposing mutations in esophageal cancer patients at such a high rate," said corresponding author Manish Gala, MD, of the Division of Gastroenterology at Massachusetts General Hospital (MGH).
"To put that into perspective, the prevalence of such mutations is 7–10% in pancreatic adenocarcinoma, and genetic testing has been recommended for all individuals diagnosed with this cancer. Given the similar prevalence in EAC, universal genetic testing should be considered for this cancer as well."
Notably, the researchers found that EAC patients with cancer-predisposing mutations had developed EAC across the age spectrum, implying that simply having a mutation did not trigger EAC; rather, BE and other environmental factors are likely additional prerequisites for cancer. Still, findings suggest that these "germline" cancer-predisposing mutations, which are present at conception and therefore found in every cell of a patient, may accelerate genomic instability that increases the likelihood of progression from BE to EAC.
This study was based on genomic data from 640 individuals with EAC, pooled from public U.S. And U.K. Databases. A total of 59 patients had highly rare, cancer-predisposing germline mutations, most commonly in the ATM gene. To validate these results, the researchers also analyzed nearly 300 individuals from MGH cohorts who either had EAC or BE with high-grade dysplasia (a precursor to EAC), BE without cancer progression after 10 or more years, or who were healthy nonagenarians.
Again, they found that germline mutations, especially in the ATM gene, were the most prevalent in EAC patients, with evidence that in people who progressed to EAC, there may be additional epigenetic changes that cause abnormalities in ATM expression compared to non-progressors.
Results from the study also shed light on the existing question of why approximately 30% of EAC patients do not have a common cancer-causing mutation, a TP53 mutation, "within" their tumor cells. The researchers found that EAC patients "without" TP53 mutations in their tumors were instead much more likely to have pathogenic germline mutations, and at a rate comparable to that of ovarian cancer, which is known to be a highly genetics-dependent disease.
Collectively, results support the idea that genetic testing can help risk-stratify EAC patients, due to the important role germline mutations appear to play in triggering progression from BE to EAC.
Going forward, the researchers plan to derive estimates of EAC risk based on gene-specific mutations, a task that will require larger study cohorts. Furthermore, they are using their knowledge of the germline mutations common in EAC (such as ATM mutations) to repurpose existing therapies that may be useful for treating EAC, with two drug candidates already identified.
"The key takeaway from this study is that if someone is progressing toward EAC from BE, performing genetic testing is probably warranted," Gala said. "For people who already know they have a mutation, we will still need more data to figure out how to best care for these individuals, but a one-size-fits-all approach to screening may not be appropriate."
More information: Minyi Lee et al, Germline Determinants of Esophageal Adenocarcinoma, Gastroenterology (2023). DOI: 10.1053/j.Gastro.2023.07.015
Citation: Identification of genetic drivers for esophageal cancer creates new opportunity for screening, treatment (2023, July 27) retrieved 28 July 2023 from https://medicalxpress.Com/news/2023-07-identification-genetic-drivers-esophageal-cancer.Html
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