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Endometrial Adenocarcinoma

Disease Details

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Description: Endometrial adenocarcinoma is a type of cancer that originates in the lining of the uterus, known as the endometrium.
Type: Endometrial adenocarcinoma is a type of cancer that originates in the lining of the uterus (endometrium). It is generally sporadic, meaning it usually occurs by chance and is not inherited. However, a small percentage of cases can be associated with hereditary conditions, such as Lynch syndrome (hereditary nonpolyposis colorectal cancer), which are passed down in an autosomal dominant manner.
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: Endometrial adenocarcinoma typically has a good prognosis, especially if detected early. The prognosis can vary depending on factors such as the stage of the cancer at diagnosis, the grade of the tumor, the patient's age, and overall health. Early-stage endometrial adenocarcinoma generally has high survival rates, while advanced stages may have a less favorable outlook. Comprehensive treatment plans and regular follow-up care are critical for improving outcomes. Nanotechnology is being explored in cancer treatment, including for endometrial adenocarcinoma, but it's still largely in the research phase and not yet a standard of care.
Onset: Endometrial adenocarcinoma is the most common type of endometrial cancer. It generally develops after menopause, typically affecting women aged 50 and older. However, it can occur earlier, especially in those with risk factors such as obesity, a history of endometrial hyperplasia, or a family history of certain cancers.
Prevalence: Endometrial adenocarcinoma is the most common type of endometrial cancer, which originates in the lining of the uterus. It primarily affects postmenopausal women. The prevalence of endometrial cancer in the United States is significant, with an estimated 66,200 new cases and 13,030 deaths expected in 2023, according to the American Cancer Society. This type of cancer accounts for about 90% of all uterine cancers. Globally, endometrial cancer is the sixth most commonly diagnosed cancer in women.
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 adenocarcinoma, a type of cancer originating in the lining of the uterus, is not inherently intractable. The disease's prognosis and treatment effectiveness heavily depend on several factors, including the stage at diagnosis, the tumor grade, and the patient's overall health. In early stages, it often responds well to standard treatments such as surgery (hysterectomy), radiation therapy, and sometimes chemotherapy or hormone therapy. Advanced stages may be more challenging to treat but are not necessarily intractable, as novel therapies and clinical trials continue to improve outcomes. Early detection and appropriate treatment are crucial for better management and potential cure.
Disease Severity: Endometrial adenocarcinoma is a type of cancer that originates from the lining of the uterus, known as the endometrium. The severity of the disease can vary widely based on several factors, including the stage at diagnosis, the grade of the tumor, and the patient's overall health.

1. **Stage:**
- **Stage I:** Cancer is confined to the uterus and has not spread to other parts of the body. Generally considered early-stage and has a better prognosis.
- **Stage II:** Cancer has spread to the connective tissue of the cervix but not outside the uterus.
- **Stage III:** Cancer has spread beyond the uterus, but is still within the pelvic region. This includes spread to the ovaries, fallopian tubes, vagina, and/or regional lymph nodes.
- **Stage IV:** Cancer has spread to the bladder, bowel, or distant organs, representing advanced disease with a poorer prognosis.

2. **Grade:**
- The grade of the tumor is an indication of how much the cancer cells resemble normal endometrial cells under the microscope.
- **Grade 1 (low grade):** Cells look more like normal cells and tend to grow slowly.
- **Grade 2 (intermediate grade):** Cells have more abnormalities than grade 1.
- **Grade 3 (high grade):** Cells look very different from normal cells and tend to grow more quickly and spread more easily.

3. **Other Factors:**
- **Lymphovascular invasion:** Presence of cancer cells in the blood vessels or lymph vessels can indicate a higher risk of spread.
- **Patient factors:** Age, overall health, and presence of other medical conditions can also affect disease severity and prognosis.

Timely diagnosis and appropriate treatment significantly improve outcomes, with early-stage endometrial adenocarcinoma generally having a more favorable prognosis compared to advanced-stage disease.
Healthcare Professionals: Disease Ontology ID - DOID:2870
Pathophysiology: 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: Carrier status is not applicable to endometrial adenocarcinoma. This form of cancer originates in the lining of the uterus and is generally linked to risk factors such as hormonal imbalances, obesity, and genetic mutations like Lynch syndrome, rather than being a condition passed on by carriers.
Mechanism: Endometrial adenocarcinoma is a type of cancer that originates in the lining of the uterus (endometrium).

**Mechanism:**
The disease typically develops when the endometrial cells undergo malignant transformation, often driven by an imbalance between cell proliferation and apoptosis. This process can be associated with factors such as obesity, hormone replacement therapy, and other conditions that lead to prolonged exposure to estrogen without the counterbalancing effect of progesterone.

**Molecular Mechanisms:**
1. **Genetic Mutations:**
- Mutations in the PTEN gene, which is a tumor suppressor gene, are commonly seen. PTEN mutations lead to unregulated cell growth and survival.
- Alterations in PIK3CA, which plays a role in the PI3K/AKT signaling pathway, are also frequently observed and contribute to cancer progression.
- Mutations in KRAS, a gene involved in cell signaling pathways, can lead to increased cell proliferation.

2. **Microsatellite Instability (MSI):**
- Defects in the DNA mismatch repair system can result in MSI, which is observed in a subset of endometrial adenocarcinomas and is associated with a distinct pathway of carcinogenesis.

3. **Hormonal Influence:**
- Excessive estrogen stimulation without the moderating effect of progesterone can lead to over-proliferation of the endometrial lining and mutated cell growth.

4. **Epigenetic Changes:**
- Alterations in DNA methylation patterns and histone modifications can affect gene expression and contribute to the development and progression of endometrial adenocarcinoma.

Understanding these mechanisms is critical for diagnosing, treating, and developing targeted therapies for endometrial adenocarcinoma.
Treatment: Treatment for endometrial adenocarcinoma typically involves a combination of the following approaches:

1. **Surgery:** The primary treatment is often a hysterectomy, which involves the removal of the uterus, and may include the removal of the fallopian tubes and ovaries (salpingo-oophorectomy). Lymph node dissection may also be performed.

2. **Radiation Therapy:** This can be used as an adjunct to surgery to eliminate any remaining cancer cells or as primary treatment if surgery is not an option.

3. **Hormone Therapy:** Used particularly for advanced or recurrent endometrial adenocarcinoma. Medications like progesterone can help slow the growth of cancer cells that are hormone receptor-positive.

4. **Chemotherapy:** Typically used for advanced, recurrent, or high-grade tumors. Common chemotherapy drugs include carboplatin and paclitaxel.

5. **Targeted Therapy:** In some cases, molecularly targeted therapies may be employed, especially in tumors that exhibit specific genetic mutations.

The specific treatment plan depends on the stage and grade of the cancer, as well as the patient's overall health and preferences.
Compassionate Use Treatment: Compassionate use treatment and off-label or experimental treatments for endometrial adenocarcinoma involve options that are not standardly approved but may be explored under specific circumstances:

1. **Compassionate Use Treatments:**
- **Pembrolizumab (Keytruda):** May be used on a compassionate basis for patients with advanced or recurrent endometrial carcinoma, particularly in cases with mismatched repair deficiency (dMMR) or high microsatellite instability (MSI-H).
- **Lenvatinib (Lenvima) in combination with Pembrolizumab:** This combination has been used under compassionate use programs for patients with advanced and treatment-resistant endometrial cancer.

2. **Off-label or Experimental Treatments:**
- **Hormonal Therapies:** Agents like tamoxifen or aromatase inhibitors might be prescribed off-label in specific cases, particularly in hormone receptor-positive endometrial cancers.
- **Immunotherapy:** Certain immune checkpoint inhibitors aside from pembrolizumab are being studied experimentally.
- **Targeted Therapies:** Investigational drugs targeting specific genetic mutations, such as PI3K inhibitors, or therapies aimed at VEGF receptors, may be used in clinical trials or off-label scenarios.
- **Combination Therapies:** Experimental protocols may include the combination of chemotherapy, targeted therapy, and immunotherapy to assess synergy and improved outcomes in clinical trials.

Close collaboration with oncologists and participation in clinical trials are often essential to accessing these treatments.
Lifestyle Recommendations: Lifestyle recommendations for individuals with endometrial adenocarcinoma typically focus on overall health and well-being to support treatment and recovery. Here are some general guidelines:

1. **Healthy Diet**: Consume a balanced diet rich in fruits, vegetables, lean proteins, and whole grains. Limit processed foods, red meats, and high-fat dairy products.

2. **Maintain a Healthy Weight**: Obesity is a risk factor for endometrial cancer, so maintaining a healthy weight through diet and exercise is beneficial.

3. **Physical Activity**: Engage in regular physical activity, such as walking, swimming, or yoga, to improve overall health and reduce stress.

4. **Quit Smoking**: Smoking is harmful to overall health and can complicate treatment and recovery. Seek resources to help quit if you are a smoker.

5. **Limit Alcohol Consumption**: Excessive alcohol intake can have negative effects on health, including potentially impacting cancer progression and treatment.

6. **Regular Medical Follow-Up**: Keep all scheduled appointments with your healthcare team to monitor your condition and manage any side effects from treatment.

7. **Manage Stress**: Practice stress-reducing techniques such as meditation, deep breathing exercises, or seeking support from a counselor or support group.

8. **Stay Hydrated**: Ensure adequate fluid intake, particularly water, to support bodily functions and overall health.

Always consult with your healthcare provider for personalized advice tailored to your specific condition and treatment plan.
Medication: Medication for endometrial adenocarcinoma typically includes hormonal therapies and chemotherapy. Hormonal treatments often involve progestins and sometimes estrogens, while chemotherapy may include combinations such as paclitaxel and carboplatin. The specific regimen depends on the stage and characteristics of the cancer, as well as patient health. Always consult with an oncologist for personalized treatment plans.
Repurposable Drugs: Repurposable drugs for endometrial adenocarcinoma include:

1. **Metformin**: Originally used for type 2 diabetes, it has shown promise in reducing cancer cell proliferation.
2. **Statins**: Typically used to lower cholesterol, they may have anti-cancer properties by inducing apoptosis in cancer cells.
3. **Aspirin**: Known for its anti-inflammatory effects, it may help in reducing cancer risk and progression.
4. **Bisphosphonates**: Used to treat osteoporosis, they may inhibit metastasis and tumor growth.
5. **Progestins**: Hormonal therapy drugs initially used for birth control may help in certain hormone-responsive endometrial cancers.
Metabolites: For endometrial adenocarcinoma, several metabolites have been studied in relation to the disease, although specific biomarkers are still under extensive research. Some metabolites of interest include:

1. **Lactic acid:** Often elevated due to the Warburg effect, where cancer cells prefer glycolysis over oxidative phosphorylation even in the presence of oxygen.
2. **Glucose and related glycolytic intermediates:** Their levels can shift due to altered glucose metabolism in cancer cells.
3. **Amino acids such as glutamine and glycine:** These may be utilized differently by cancer cells for energy and biosynthesis.
4. **Lipid metabolites:** Changes in lipid metabolism, including altered levels of phosphatidylcholines, can be observed.
5. **Hormone metabolites:** Such as estradiol and its derivatives, considering endometrial cancer's association with hormonal changes.

These metabolites can help in understanding the metabolic alterations in endometrial adenocarcinoma and might serve as potential biomarkers for diagnosis or targets for therapy in the future.
Nutraceuticals: Currently, there is no strong evidence to support the use of nutraceuticals specifically for the treatment or prevention of endometrial adenocarcinoma. Nutraceuticals are products derived from food sources with extra health benefits in addition to their basic nutritional values, but their efficacy and safety in treating specific types of cancer like endometrial adenocarcinoma have not been conclusively proven. It's important to consult healthcare professionals for personalized medical advice.

If you have more specific questions or need detailed information about endometrial adenocarcinoma, please let me know.
Peptides: For endometrial adenocarcinoma, peptides can be relevant in several contexts, including diagnostic markers, therapeutic agents, and vaccine development. Peptides like CA-125, although more commonly associated with ovarian cancer, can sometimes be elevated in endometrial adenocarcinoma. Research also explores peptides for targeted therapy and immunotherapy to trigger an immune response against cancer cells.

Nanotechnology (nan) plays a significant role in enhancing the detection and treatment of endometrial adenocarcinoma. Nanoparticles can be engineered to deliver chemotherapeutic agents directly to cancer cells, reducing side effects and improving efficacy. Additionally, they are used in imaging for better visualization of tumors during diagnostic procedures. Nanoparticle-based systems can also facilitate personalized medicine by targeting specific molecular pathways involved in the cancer.