Endometrial Cancer
Disease Details
Family Health Simplified
- Description
- Endometrial cancer is a type of cancer that begins in the lining of the uterus, known as the endometrium.
- Type
- Endometrial cancer is typically classified as a type of cancer that affects the lining of the uterus, known as the endometrium. Most cases are sporadic and are not caused by inherited genetic mutations. However, a minority of cases can be associated with inherited genetic syndromes, such as Lynch syndrome (also known as hereditary nonpolyposis colorectal cancer, HNPCC). In those cases, the genetic transmission is autosomal dominant, meaning a single copy of the mutated gene can increase the risk of developing the cancer.
- Signs And Symptoms
- Vaginal bleeding or spotting in women after menopause occurs in 90% of endometrial cancer. Bleeding is especially common with adenocarcinoma, occurring in two-thirds of all cases. Abnormal menstrual cycles or extremely long, heavy, or frequent episodes of bleeding in women before menopause may also be a sign of endometrial cancer.Symptoms other than bleeding are not common. Other symptoms include thin white or clear vaginal discharge in postmenopausal women. More advanced disease shows more obvious symptoms or signs that can be detected on a physical examination. The uterus may become enlarged or the cancer may spread, causing lower abdominal pain or pelvic cramping. Painful sexual intercourse or painful or difficult urination are less common signs of endometrial cancer. The uterus may also fill with pus (pyometrea). Of women with these less common symptoms (vaginal discharge, pelvic pain, and pus), 10–15% have cancer.
- Prognosis
- The prognosis of endometrial cancer largely depends on the stage at which it is diagnosed, the tumor grade, and other individual health factors. Early-stage endometrial cancer has a relatively favorable prognosis, with high survival rates. Advanced stages or high-grade tumors generally have a poorer prognosis. Treatment options and responses also significantly influence outcomes. Regular follow-ups and appropriate management are crucial for improving prognostic outcomes.
- Onset
- Endometrial cancer, also known as uterine cancer, typically has an onset after menopause, with most cases occurring in women aged 50 to 70 years. However, it can develop in younger women as well, particularly those with risk factors such as obesity, estrogen therapy, or genetic predispositions.
- Prevalence
- Endometrial cancer is one of the most common gynecologic cancers, particularly in postmenopausal women. In the United States, it is the fourth most common cancer among women, with an estimated 66,200 new cases diagnosed in 2021. The lifetime risk for a woman to develop endometrial cancer is approximately 2%-3%. Prevalence is higher in high-income countries due to factors such as obesity, lower fertility rates, and increased longevity.
- Epidemiology
- As of 2014, approximately 320,000 women are diagnosed with endometrial cancer worldwide each year and 76,000 die, making it the sixth most common cancer in women. It is more common in developed countries, where the lifetime risk of endometrial cancer in women is 1.6%, compared to 0.6% in developing countries. It occurs in 12.9 out of 100,000 women annually in developed countries.In the United States, endometrial cancer is the most frequently diagnosed gynecologic cancer and, in women, the fourth most common cancer overall, representing 6% of all cancer cases in women. In that country, as of 2014 it was estimated that 52,630 women were diagnosed yearly and 8,590 would die from the disease. Northern Europe, Eastern Europe, and North America have the highest rates of endometrial cancer, whereas Africa and West Asia have the lowest rates. Asia saw 41% of the world's endometrial cancer diagnoses in 2012, whereas Northern Europe, Eastern Europe, and North America together comprised 48% of diagnoses. Unlike most cancers, the number of new cases has risen in recent years, including an increase of over 40% in the United Kingdom between 1993 and 2013. Some of this rise may be due to the increase in obesity rates in developed countries, increasing life expectancies, and lower birth rates. The average lifetime risk for endometrial cancer is approximately 2–3% in people with uteruses. In the UK, approximately 7,400 cases are diagnosed annually, and in the EU, approximately 88,000.Endometrial cancer appears most frequently during perimenopause (the period just before, just after, and during menopause), between the ages of 50 and 65; overall, 75% of endometrial cancer occurs after menopause. Women younger than 40 make up 5% of endometrial cancer cases and 10–15% of cases occur in women under 50 years of age. This age group is at risk for developing ovarian cancer at the same time. The worldwide median age of diagnosis is 63 years of age; in the United States, the average age of diagnosis is 60 years of age. White American women are at higher risk for endometrial cancer than black American women, with a 2.88% and 1.69% lifetime risk respectively. Japanese-American women and American Latina women have a lower rates and Native Hawaiian women have higher rates.
- Intractability
- Endometrial cancer is not considered intractable. It is often treatable, especially when detected early. Treatment options can include surgery (such as hysterectomy), radiation therapy, hormone therapy, and chemotherapy. Early-stage endometrial cancer, in particular, has a high survival rate, but the prognosis may vary depending on the stage and grade of the cancer at diagnosis.
- Disease Severity
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Endometrial cancer, primarily affecting the lining of the uterus, exhibits varying degrees of severity based on the following factors:
1. **Stage**:
- **Stage I**: Cancer is confined to the uterus.
- **Stage II**: Cancer has spread to the cervix.
- **Stage III**: Cancer extends beyond the uterus to nearby tissues.
- **Stage IV**: Cancer has spread to distant organs.
2. **Grade**: Refers to the appearance of cancer cells under a microscope.
- **Grade 1 (low grade)**: Cells look more like normal cells and tend to grow slowly.
- **Grade 3 (high grade)**: Cells look very different from normal cells and tend to grow more rapidly.
3. **Histological Type**: The specific type of cell structure can influence severity.
- Endometrioid adenocarcinoma (most common and often less aggressive).
- Serous carcinoma and clear cell carcinoma (less common, more aggressive).
Severity increases with higher stages, higher grades, and more aggressive histological types, affecting prognosis and treatment approaches. - Healthcare Professionals
- Disease Ontology ID - DOID:1380
- Pathophysiology
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Endometrial cancer forms when there are errors in normal endometrial cell growth. Usually, when cells grow old or get damaged, they die, and new cells take their place. Cancer starts when new cells form unneeded, and old or damaged cells do not die as they should. The buildup of extra cells often forms a mass of tissue called a growth or tumor. These abnormal cancer cells have many genetic abnormalities that cause them to grow excessively.In 10–20% of endometrial cancers, mostly Grade 3 (the highest histologic grade), mutations are found in a tumor suppressor gene, commonly p53 or PTEN. In 20% of endometrial hyperplasias and 50% of endometrioid cancers, PTEN has a loss-of-function mutation or a null mutation, making it less effective or completely ineffective. Loss of PTEN function leads to up-regulation of the PI3k/Akt/mTOR pathway, which causes cell growth. The p53 pathway can either be suppressed or highly activated in endometrial cancer. When a mutant version of p53 is overexpressed, the cancer tends to be particularly aggressive. P53 mutations and chromosome instability are associated with serous carcinomas, which tend to resemble ovarian and Fallopian carcinomas. Serous carcinomas are thought to develop from endometrial intraepithelial carcinoma.
PTEN and p27 loss of function mutations are associated with a good prognosis, particularly in obese women. The Her2/neu oncogene, which indicates a poor prognosis, is expressed in 20% of endometrioid and serous carcinomas. CTNNB1 (beta-catenin; a transcription gene) mutations are found in 14–44% of endometrial cancers and may indicate a good prognosis, but the data is unclear. Beta-catenin mutations are commonly found in endometrial cancers with squamous cells. FGFR2 mutations are found in approximately 10% of endometrial cancers, and their prognostic significance is unclear. SPOP is another tumor suppressor gene found to be mutated in some cases of endometrial cancer: 9% of clear cell endometrial carcinomas and 8% of serous endometrial carcinomas have mutations in this gene.Type I and Type II cancers (explained below) tend to have different mutations involved. ARID1A, which often carries a point mutation in Type I endometrial cancer, is also mutated in 26% of clear cell carcinomas of the endometrium, and 18% of serous carcinomas. Epigenetic silencing and point mutations of several genes are commonly found in Type I endometrial cancer. Mutations in tumor suppressor genes are common in Type II endometrial cancer. PIK3CA is commonly mutated in both Type I and Type II cancers. In women with Lynch syndrome-associated endometrial cancer, microsatellite instability is common.Development of an endometrial hyperplasia (overgrowth of endometrial cells) is a significant risk factor because hyperplasias can and often do develop into adenocarcinoma, though cancer can develop without the presence of a hyperplasia. Within ten years, 8–30% of atypical endometrial hyperplasias develop into cancer, whereas 1–3% of non-atypical hyperplasias do so. An atypical hyperplasia is one with visible abnormalities in the nuclei. Pre-cancerous endometrial hyperplasias are also referred to as endometrial intraepithelial neoplasia. Mutations in the KRAS gene can cause endometrial hyperplasia and therefore Type I endometrial cancer. Endometrial hyperplasia typically occurs after the age of 40. Endometrial glandular dysplasia occurs with an overexpression of p53, and develops into a serous carcinoma. - Carrier Status
- Endometrial cancer is primarily associated with genetic mutations that occur sporadically in the cells of the endometrium. Carrier status for hereditary syndromes like Lynch syndrome (HNPCC) can increase the risk of developing endometrial cancer. Genetic testing is recommended for individuals with a family history of cancers associated with Lynch syndrome.
- Mechanism
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Endometrial cancer primarily affects the lining of the uterus, known as the endometrium. The disease arises due to uncontrolled cell division within the endometrial tissue. Several molecular mechanisms contribute to the development and progression of endometrial cancer:
1. **Genetic Mutations**: Mutations in specific genes can drive the transformation of normal endometrial cells into cancerous cells. Commonly mutated genes include PTEN, PIK3CA, KRAS, and TP53. PTEN mutations, for instance, lead to the inactivation of its tumor suppressor function, promoting uncontrolled cell growth.
2. **Hormonal Influences**: Estrogen plays a significant role in the pathogenesis of endometrial cancer. Unopposed estrogen exposure, which is not balanced by progesterone, can lead to enhanced cellular proliferation and increased risk of mutations within the endometrial lining.
3. **Epigenetic Changes**: Alterations in DNA methylation and histone modification can affect gene expression without changing the DNA sequence. These epigenetic changes can result in the silencing of tumor suppressor genes and activation of oncogenes, contributing to cancer development and progression.
4. **PI3K/AKT/mTOR Pathway**: This signaling pathway is frequently activated in endometrial cancer due to mutations in genes such as PTEN and PIK3CA. Activation of this pathway promotes cell proliferation, survival, and growth, facilitating tumor development.
5. **Microsatellite Instability (MSI)**: MSI is a condition of genetic hypermutability that results from impaired DNA mismatch repair. Tumors with high levels of MSI tend to have numerous mutations, some of which can drive cancer progression. About 20-30% of endometrial cancers exhibit MSI.
6. **Wnt/β-catenin Pathway**: Dysregulation of this signaling pathway through mutations in genes like CTNNB1 can lead to altered cell proliferation and differentiation, contributing to tumorigenesis.
These molecular mechanisms collectively contribute to the heterogeneity and complexity of endometrial cancer, influencing both its clinical presentation and response to therapy. Researchers are continuously working to better understand these pathways to develop targeted treatments and improve patient outcomes. - Treatment
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Endometrial cancer, primarily originating in the lining of the uterus, often involves treatment options such as:
1. **Surgery**: The most common treatment is a hysterectomy, which involves the removal of the uterus. In some cases, bilateral salpingo-oophorectomy (removal of both ovaries and fallopian tubes) is also performed.
2. **Radiation Therapy**: This method uses high-energy rays to target and kill cancer cells. It's often used in conjunction with surgery or for those who cannot undergo surgical procedures.
3. **Hormone Therapy**: This treatment involves medications that alter hormone levels to slow the growth of cancer cells. It's typically used for advanced or recurrent endometrial cancer.
4. **Chemotherapy**: Chemotherapy uses drugs to kill rapidly growing cancer cells. It's often utilized if the cancer has spread beyond the uterus or in combination with other treatments.
5. **Targeted Therapy and Immunotherapy**: These newer treatments are designed to target specific aspects of cancer cells or to help the immune system better identify and attack cancer cells.
The choice of treatment depends on the stage and grade of the cancer, as well as the overall health and preferences of the patient. - Compassionate Use Treatment
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Compassionate use treatment for endometrial cancer involves providing patients with access to investigational treatments outside of clinical trials when no other satisfactory treatment options are available.
Off-label treatments refer to the use of approved medications in a manner not specified in the official labeling. For endometrial cancer, this might include:
- Use of chemotherapy drugs such as cisplatin, carboplatin, or doxorubicin in ways not explicitly approved.
- Hormonal therapies such as megestrol acetate or tamoxifen.
- Targeted therapies including drugs like bevacizumab, which is typically approved for other types of cancers.
Experimental treatments include therapies currently being tested in clinical trials, such as:
- Immunotherapy drugs like pembrolizumab.
- Targeted therapies aimed at specific genetic mutations within the cancer cells.
- Novel combinations of drugs or new chemotherapy protocols.
Patients considering compassionate use, off-label, or experimental treatments should have thorough discussions with their healthcare providers to understand potential benefits and risks. - Lifestyle Recommendations
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For managing and potentially reducing the risk of endometrial cancer, here are some lifestyle recommendations:
1. **Maintain a Healthy Weight**: Obesity is a significant risk factor for endometrial cancer. Aim to maintain a healthy weight through a balanced diet and regular exercise.
2. **Healthy Diet**: Consume a diet rich in fruits, vegetables, whole grains, and lean proteins. Limiting red and processed meats and reducing sugar and saturated fat intake can also be beneficial.
3. **Regular Exercise**: Engaging in regular physical activity can help maintain a healthy weight and lower your risk. Aim for at least 150 minutes of moderate-intensity aerobic activity each week.
4. **Limit Alcohol Intake**: Reducing or eliminating alcohol consumption can decrease your risk of various cancers, including endometrial cancer.
5. **Avoid Tobacco**: Smoking increases the risk of many cancers. Quitting smoking can improve overall health and potentially reduce the risk of endometrial cancer.
6. **Control Diabetes**: Manage diabetes effectively through medication, diet, and lifestyle changes, as uncontrolled diabetes can increase the risk of endometrial cancer.
7. **Hormone Balancing**: Discuss hormone replacement therapy (HRT) with a healthcare provider, especially if you are considering it for managing menopausal symptoms. Certain types of HRT can increase the risk of endometrial cancer.
8. **Regular Screening and Check-ups**: Regular gynecological exams can help in the early detection of any abnormalities. If symptoms such as abnormal vaginal bleeding occur, seek prompt medical advice.
These recommendations can help reduce the risk of endometrial cancer and contribute to overall well-being. - Medication
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For endometrial cancer, medications are often part of the treatment regimen and may include:
1. **Hormonal Therapy**: Used primarily for advanced or recurrent endometrial cancer. This includes:
- **Progestins**: Medroxyprogesterone acetate (Provera) or megestrol acetate (Megace) to slow the growth of cancer cells.
- **Tamoxifen**: Sometimes used to block estrogen receptors.
- **Aromatase Inhibitors**: Drugs like letrozole, anastrozole, or exemestane to lower estrogen levels.
- **Gonadotropin-Releasing Hormone (GnRH) Agonists**: Drugs like leuprolide to reduce estrogen levels.
2. **Chemotherapy**: Often used for advanced cases or if the cancer has recurred. Common drugs include:
- **Paclitaxel**
- **Carboplatin**
- **Doxorubicin**
3. **Targeted Therapy**: Involves drugs that target specific aspects of cancer cells. Examples include:
- **Pembrolizumab**: An immune checkpoint inhibitor used for certain types of advanced or recurrent cases.
It's important that treatment plans are tailored to the individual patient based on the stage and characteristics of the cancer. - Repurposable Drugs
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There are various drugs that are currently being explored for repurposing in the treatment of endometrial cancer. Some of these repurposable drugs include:
1. **Metformin**: Originally used for type 2 diabetes, metformin has shown potential in inhibiting cancer cell growth and improving survival rates in endometrial cancer patients.
2. **Aspirin**: Commonly used as an anti-inflammatory and anti-coagulant, aspirin may help reduce the risk and progression of endometrial cancer due to its anti-inflammatory properties.
3. **Statins**: Typically used to lower cholesterol, statins have been investigated for their potential to suppress tumor growth in various types of cancer, including endometrial cancer.
4. **Bisphosphonates**: Used to treat osteoporosis, these drugs may have anti-tumor effects and are being studied for their capability to inhibit cancer cell proliferation.
These drugs are being investigated in clinical trials to determine their effectiveness and safety in treating endometrial cancer. Always consult with a healthcare professional before considering any change in treatment. - Metabolites
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Endometrial cancer is often associated with alterations in specific metabolites. Relevant metabolites include:
1. **Glycolytic Pathway Metabolites**: Increased levels of glucose and lactate, indicating a shift towards aerobic glycolysis (Warburg effect).
2. **Lipid Metabolism**: Altered levels of fatty acids, glycerophospholipids, and sphingolipids.
3. **Amino Acids**: Changes in concentrations of amino acids like glutamine, glycine, and serine.
4. **Nucleotide Metabolism**: Altered levels of nucleotides like adenosine and thymidine.
These metabolic changes can provide insights into tumor biology and potential therapeutic targets for endometrial cancer. - Nutraceuticals
- Nutraceuticals are food-derived products that offer health and medical benefits, including the prevention and treatment of diseases. While some nutraceuticals are being explored for their potential role in reducing the risk or aiding in the management of endometrial cancer, current research is limited and not yet conclusive. Commonly studied nutraceuticals for general cancer prevention and support include vitamins (like Vitamin D), antioxidants (such as curcumin from turmeric), and omega-3 fatty acids. It is important for patients to consult healthcare providers before using nutraceuticals for cancer management.
- Peptides
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Peptides related to endometrial cancer are currently being studied for their potential roles in diagnostics, prognostics, and therapeutics. These peptides can serve as biomarkers for early detection or as targets for peptide-based therapies, which aim to specifically attack cancer cells while sparing normal tissue.
Nanotechnology in endometrial cancer involves the use of nanoparticles to enhance drug delivery, improve imaging techniques, and develop novel therapeutic approaches. Nanoparticles can be engineered to carry chemotherapeutic agents directly to cancer cells, minimizing side effects and improving the efficacy of treatment. They also hold promise in enhancing the capabilities of diagnostic imaging, enabling earlier and more accurate detection of cancerous lesions.