Endometrial Cancer – Causes, Signs and symptoms

Endometrial Cancer

Also called: Endometrial Carcinoma

Reviewed By:
Martin E. Liebling, M.D., FACP
Mark Oren, M.D., FACP

Summary

Endometrial cancer is a type of cancer that is characterized by of the growth of abnormal, malignant cells in the inner lining of the uterus, which is called the endometrium. The most common symptom of endometrial cancer is abnormal uterine spotting or bleeding from the vagina.

Endometrial cancer is the fourth most common cancer in American women, according to the American Cancer Society. Although the exact cause of the disease is unknown, many experts believe that estrogen levels play a large role in the development of endometrial cancer. Risk factors for the condition may include:

  • Length of menstrual span (number of years a woman menstruates)
  • Infertility
  • Obesity
  • Age
  • History of breast cancer or ovarian cancer
  • Use of estrogen medications or certain hormone blocking agents (e.g., tamoxifen)

The diagnosis of endometrial cancer typically begins with a complete medical history, physical examination and pelvic examination. If cancer is suspected, other tests, such as an endometrial biopsy (a procedure to obtain a tissue sample from the endometrium) will usually follow. Methods for treating endometrial cancer are often successful. Treatment methods may include surgery, radiation therapy, chemotherapy and hormone therapy. In many patients, a combination of these therapies may be used as treatment. Research continues to discover more about the nature of this cancer, methods of prevention and treatment and ways to reduce the risk of recurrence.

About endometrial cancer

Endometrial cancer is a type of cancer that occurs when the cells of the endometrium, the inner lining of the uterus (womb), grow out of control. Normal cells divide, grow and die in an organized manner. However, damage to DNA can cause cells to keep dividing until they form a tumor (a mass of excess tissue) that is malignant. In some cases, the cancer cells become invasive, spreading to tissues and organs outside of the endometrium (metastasis). Scientists are not certain why endometrial cancer cells develop. However, many experts believe that levels of the female hormone estrogen play an important role in the development of this disease.

Nearly three-quarters of all cases of endometrial cancer occur in women 45 to 74 years of age. It is the fourth most common cancer in American women and the most common female reproductive cancer, according to the American Cancer Society (ACS). In 2007, the ACS estimates there will be nearly 40,000 new cases of endometrial cancer in the United States. Although there was a rise in the number of cases between 1988 and 1997, the incidence of endometrial cancer has been decreasing since 1998. There are more than 500,000 women in the United States who have survived this cancer.

The ACS estimates that approximately 7,400 American women will die from endometrial cancer in 2007. However, survival is greatly improved if the cancer is diagnosed in the early stages. The 5-year survival rate is 96 percent if the cancer has not spread outside the uterus. The rate drops to 23 percent if the cancer has spread from the uterus to distant parts of the body.

Although it is commonly called uterine cancer, patients should be aware that endometrial cancer is merely one type of uterine cancer and that other, less common forms of uterine cancer do exist.

Types and differences of endometrial cancer

According to the American Cancer Society (ACS), 90 percent of all endometrial cancers develop from a layer of glandular cells called the endometrial epithelium. Cancers of these cells are called adenocarcinomas. Sometimes these glandular cells are accompanied by squamous cells (a type of cell found on the skin and the surface of the cervix). If the squamous cells appear benign (noncancerous) under a microscope, and the glandular cells appear malignant (cancerous), these tumors are known as adenoacanthomas.

If both the squamous and glandular cells look malignant, these tumors are known as adenosquamous carcinomas. Although they are different in appearance, adenosquamous carcinomas are considered to behave in the same way as pure endometrial adenocarcinomas.

Other, less common types of endometrial cancer include clear cell and papillary serous adenocarcinomas. These are different from most endometrial cancers because they tend to develop and spread more rapidly.

It is important to note that fibroids, which are benign tumors that often develop in the wall of the uterus, are not cancer. These can, however, require a hysterectomy or other treatment. Fibroids are often referred to as tumors or growths by medical professionals. Women should understand that these tumors do not mean cancer. If a hysterectomy is performed for fibroids, it is for other medical reasons, not the removal of cancer.

Risk factors and causes of endometrial cancer

Although the exact cause of endometrial cancer is unknown, there are certain risk factors that may increase an individual’s likelihood of developing this disease. The ovaries are sex glands that produce eggs and usually produce two main kinds of female hormones called estrogen and progesterone. The balance between these hormones changes every month during a woman’s menstrual cycle to produce a woman’s monthly periods and maintain the health of the endometrium. Any shift toward high cumulative exposure to estrogen increases a woman’s risk of endometrial cancer. Many of the recognized risk factors for endometrial cancer are related to exposure to estrogen. Risk factors include:

  • Obesity. According to the American Cancer Society (ACS), women who are seriously overweight have more than three times the risk of developing endometrial cancer than women of average weight. A higher level of fat tissue can raise estrogen levels in women, thereby increasin the risk of endometrial cancer.

  • Age. According to the ACS, 95 percent of endometrial cancers affect women age 40 and older. The greatest number of cases occur between the ages of 55 and 64. As a woman ages, her risk of endometrial cancer increases.

  • Early menarche (onset of menstruation). Women who start their monthly periods before the age of 12 have an increased risk of developing endometrial cancer due to extended estrogen exposure of the endometrium.

  • Late menopause. Experiencing menopause after age 50 also increases risk of endometrial cancer because of the cumulative exposure of the endometrium to estrogen.

  • Length of menstrual span (total). This factor may be more important than an individual’s age at menarche or menopause. For instance, early menarche is not as big a risk factor for women with early menopause because the endometrium has not been exposed to estrogen for a prolonged period.

  • History of infertility (the inability to conceive a child). The balance between estrogen and progesterone shifts toward more progesterone during pregnancy. Therefore, having multiple pregnancies reduces the risk of endometrial cancer, whereas women who have never been pregnant have a greater risk of developing the disease.

  • Hormone replacement therapy (HRT). HRT uses medications (progesterone and estrogen together or estrogen alone) to replace the natural hormones that are no longer produced, as with menopause. Although estrogen alone has been prescribed to treat menopause and osteoporosis, physicians have found that using estrogen on its own significantly increases the risk of endometrial cancer. Studies have shown that using progesterone and estrogen HRT (as opposed to estrogen only) may help avoid the additional risk of endometrial cancer. Women using or considering any HRT should discuss the effects with their physician and schedule regular follow-up examinations for cancer.

  • Breast or ovarian cancerovarian cancer. Patients who have had breast or ovarian cancer may have a greater risk of developing cancer of the endometrium.  Some of the reproductive, hormonal and dietary risk factors for these cancers can also increase the risk of endometrial cancer.

  • Other ovarian diseases. Certain ovarian tumors, including benign growths, produce estrogen, such as granulose-theca cell tumors. Also, women with polycystic ovaries have higher than normal levels of estrogen and lower levels of the hormone progesterone. The estrogen to progesterone ratio for both of these conditions can increase a woman’s likelihood of developing endometrial cancer.

  • Diet high in animal fat. Fatty foods are high in calories, and therefore can lead to obesity, a well-known risk factor for various diseases, including endometrial cancer. Some scientists believe that fatty foods may have a direct effect on the metabolism of estrogen, which also increases the risk of developing endometrial cancer.

  • Diabetes. For unknown reasons, women with diabetes are more likely to develop endometrial cancer than individuals without diabetes. Some physicians attribute this increased cancer risk to excess body weight because many people with type 2 diabetes are overweight. However, this theory does not explain why women with type 1 diabetes, which is not characterized by excess body weight, also have higher endometrial cancer rates.

  • Family history. Some people have an inherited tendency to develop a specific form of colon cancer, hereditary nonpolyposis colon cancer (HNPCC). Studies have shown that at least half of women with HNPCC will also develop endometrial cancer.

  • Race. White women have a greater risk of developing endometrial cancer. However, black women have a greater risk of dying from the disease.

  • Prior pelvic radiation therapy. Patients who have had radiation therapy in the past may have an increased risk of developing endometrial cancer because radiation can damage DNA, promoting the growth of some secondary cancers.

  • Tamoxifen. This antiestrogen drug is used to treat certain patients with breast cancer. It is also prescribed to lower the risk of breast cancer in women with increased risk of developing breast cancer. Even though tamoxifen is an estrogen-blocking drug, it functions like estrogen in the uterus. Therefore, patients taking tamoxifen have an increased risk of developing endometrial cancer. Those women who are prescribed tamoxifen should regularly visit their gynecologist (a physician who specializes in women’s health care and reproductive issues). In addition, these women should immediately report any signs and symptoms of endometrial cancer, which affects about one out of every 500 users of tamoxifen.

Signs and symptoms of endometrial cancer

The early signs of endometrial cancer may be ignored by many women. As the cancer progresses, the symptoms may become more severe. The most common signs and symptoms of endometrial cancer may include:

  • Abnormal spotting, bleeding or discharge from the vagina. It is especially important for post-menopausal patients to report any spotting or bleeding to their physician. Approximately 90 percent of individuals diagnosed with endometrial cancer experience postmenopausal or unusual spotting or bleeding, according to the American Cancer Society (ACS). Although this symptom can accompany certain noncancerous conditions, such as hyperplasia (an irregular increase in the number of cells in a tissue or organ), patients are urged to have an immediate medical evaluation of abnormal bleeding.

    It is important to note that the absence of visible blood in an irregular vaginal discharge does not mean that a patient is free of cancer. The ACS estimates that approximately 10 percent of endometrial cancers are accompanied by white rather than bloody discharge.
  • Pelvic mass and/or pain and weight loss. These symptoms typically occur in the later stages of endometrial cancer. However, failure to seek prompt medical attention may allow the cancer to progress even further, thereby reducing the odds of successful treatment.
  • General weakness or fatigue
  • Difficult or painful urination
  • Painful intercourse

Awareness of the signs and symptoms of endometrial cancer and discussing them with a physician in a timely manner results in early detection of the disease in most cases. Early detection of endometrial cancer increases the likelihood that treatment will be successful. However, some cases of endometrial cancer may become advanced before recognizable signs and symptoms occur.

Diagnosis methods for endometrial cancer

There are no early detection tests or examinations for women who are at normal risk of developing endometrial cancer. If women exhibit signs and symptoms of the condition (e.g., abnormal spotting, bleeding or discharge; pelvic mass and/or pain and weight loss), testing is mandatory.

Pelvic exams are successful in finding some cancers of the female reproductive system. However, they are not very effective in detecting early endometrial cancers. Although a Pap test can occasionally identify some early endometrial cancers, most cancers are not diagnosed with this test. However, the Pap test has proven very effective in finding early cervical cancers. The American Cancer Society (ACS) recommends regular cervical cancer screenings for most women beginning at age 21 or approximately three years after they first engage in vaginal intercourse. Certain groups of women may not require a cervical cancer screening, such as those who have had a complete hysterectomy (surgical removal of the cervix and uterus) for reasons other than cervical precancer or cancer.

The ACS also recommends that all menopausal patients and those with increased risk of developing endometrial cancer be informed of their risk, and immediately notify their physician if they experience any irregular uterine bleeding. Annual testing, including endometrial biopsy, should be offered for women age 35 and older with a family history of hereditary nonpolyposis colon cancer (HNPCC), which is a risk factor for endometrial cancer. This includes:

  • Patients known to carry gene mutations associated with HNPCC
  • Patients who are likely to carry HNPCC-associated gene mutations
  • Patients with a family history of colon cancer, who have not undergone genetic testing

Diagnosis of endometrial cancer typically begins with a complete medical history, physical examination and pelvic examination. If cancer is suspected, the patient may be referred to a gynecologic oncologist, a physician who specializes in treating female reproductive cancers. The following tests may also be performed:

  • Endometrial tissue sampling. To determine the presence of cancer, the physician will remove a sample of endometrial tissue for examination under a microscope. The physician can obtain this tissue through an endometrial biopsy or by dilation and curettage (D & C). It may be performed either with or without a hysteroscopy, a test that allows the gynecologist to view the interior of the uterus through a thin, illuminated tube. Types of biopsy include:
    • Endometrial biopsy. A procedure in which a thin, flexible tube is inserted through the cervix into the uterus, and suction is used to obtain a sample of endometrial tissue. This procedure, which takes about a minute, is typically performed in a medical office. Local anesthesia of the cervix may be used to numb the area. During and after the procedure, the patient may experience pain that resembles severe menstrual cramps, which can often be relieved with over-the-counter pain medication. Endometrial biopsy is the most common test for endometrial cancer.
    • D & C. If an endometrial biopsy is inconclusive, or does not provide a sufficient amount of tissue, a D & C must be performed. This outpatient procedure may be accompanied by a hysteroscopy. During a D & C, the cervix is dilated and tissue is scraped from the inside of the uterus using a special surgical instrument. D & C takes approximately an hour, and may require sedation or general anesthesia. Most women experience little discomfort following this procedure but some may have cramping and abdominal pain.
  • Grade 1: Less than 5 percent of the tissue looks abnormal.
  • Grade 2: Less than 50 percent of the tissue looks abnormal.
  • Grade 3: More then 50 percent of the tissue looks abnormal.
  • Imaging tests. Most patients do not require imaging tests before surgery. However, patients with cancer that appears to be advanced or recurrent may benefit from a transvaginal ultrasound(a test that creates images of the uterus using sound waves)  or other assessments. CAT scan is rarely used to diagnose endometrial cancer but may be used to determine if the cancer has spread to other tissues or organs. Magnetic resonance imaging (MRI) scans may be used to evaluate how far the cancer has spread into the uterus.
  • Blood tests. The physician may also order tests to measure hormone levels or a complete blood count (CBC) to ensure that the patient can undergo surgery safely. In addition, the CA 125 blood test can identify substances released into the bloodstream by some endometrial cancers, but cannot be considered a reliable screening test. Very high levels of CA 125 may indicate that the cancer has spread beyond the uterus and may be used by physicians to help determine the need for surgery.
  • Other tests. The physician may perform cystoscopyor proctoscopy (examination of the bladder or rectum, respectively, through an illuminated tube).

Treatment & prevention of endometrial cancer

Though most cases of endometrial cancer are not preventable, women can reduce the likelihood of developing this disease by avoiding known risk factors, such as obesity and closely monitoring diabetes. Using oral contraceptives (birth control pills) also may help decrease the risk of the disease. Women who remain on birth control pills for a long time have the lowest risk. The protection agains endometrial cancer continues for at least 10 years after stopping oral contraceptives, according to the American Cancer Society. In addition women should obtain proper treatment of any precancerous endometrial disorders and discuss the use of hormone replacement therapy with their physicians.

If endometrial cancer is diagnosed, a cancer care team will help plan and implement treatment for the patient. For endometrial cancer, the team may include a surgeon, medical oncologist and a gynecologist who specializes in oncology. Treatment is based on a variety of factors, including the patient’s age and health status as well as the stage of the cancer. Patients may choose to get a second opinion about their condition prior to beginning treatment. The basic types of treatment for endometrial cancer include:

  • Surgery. Complete abdominal hysterectomy (the removal of the entire uterus, cervix, fallopian tubes and ovaries through an abdominal incision) is the primary surgical treatment for endometrial cancer. This surgery requires general or regional anesthesia, and typically requires a three- to five-day hospitalization. Complete recovery generally takes approximately four to six weeks.  All hysterectomies result in infertility. Other surgeries may include:
    • Radical hysterectomy.  The removal of the entire uterus as well as surrounding tissues and part of the vagina. The average hospital stay following this procedure is approximately seven days, with a recovery period of one to two months. 
    • Pelvic and paraaortic lymph node dissection. The removal of some lymph nodes in the pelvis and near the aorta (the primary artery that transports blood from the heart). This procedure is used to determine whether or not the cancer has spread (metastasized).
    • Laparoscopic lymph node sampling. The removal of lymph nodes using laparoscopy, which allows the physician to view the interior of the pelvis and abdomen through a tube that is inserted into a small incision. This procedure is often performed as part of a complete abdominal hysterectomy. Laparoscopy is being studied to determine if it is effective as standard treatment for endometrial cancer. Early research suggests that women who underwent laparoscopic surgery have the same cure rate as those who received abdominal surgery. However, long-term studies are needed to fully evaluate its effectiveness.
  • Radiation therapy. This type of treatment destroys or shrinks cancer cells with high-energy radiation. Types of radiation therapy include:
    • Brachytherapy (also called internal radiation therapy). Radioactive pellets are inserted into the vagina using a special applicator. This type of therapy is typically performed four to six weeks after a hysterectomy. It is used in cases where the top third of the vagina (the vaginal cuff) requires radiation treatment. Patients may require several treatments, and the radiation has minimal effect on surrounding structures, such as the rectum or bladder.

      Also, if cancer cells are found in fluid sampled during surgery, physicians may introduce a radioactive solution through a catheter into the pelvic and abdominal cavities after the surgery. This solution should not be used in conjunction with external beam radiation therapy.
    • External beam radiation therapy. This more common form of therapy concentrates highly focused radioactive beams from a machine outside the body on a targeted area. The skin that covers the treatment area is marked with permanent ink or injected dye (much like a tattoo). A custom-made mold of the pelvis and lower back helps ensure that the patient is placed in the same position during each treatment. External beam radiation therapy, which typically requires four to five weeks of five-day per week treatments, may be combined with brachytherapy in some instances.
  • Chemotherapy. Often called “chemo,” this treatment uses powerful drugs to kill cancer cells. These drugs are typically administered either intravenously or orally. After the drugs enter the patient’s bloodstream, they begin to spread throughout the body to kill cancer cells. This makes chemotherapy potentially useful in treating cancer that has spread beyond the lining of the uterus. In certain cases, combination chemotherapy drugs may be more effective in treating cancer than a single drug alone.
  • Hormone therapy. This form of treatment slows the progression of cancer cells with drugs such as progesterone and hormone-blocking drugs. These drugs are usually taken in pill form and may be taken for several years. 

    Hormone therapy also may use surgery to block organs that produce hormones. In women, the ovaries may be destroyed or rendered inactive by radiation. These procedures may slow the growth of endometrial cancer by reducing or eliminating the production of hormones.
  • Clinical trials. Patients may choose to participate in clinical trials or studies involving promising new or experimental treatment methods. The patient’s oncologist can best determine if a patient is eligible for aclinical trial and provide information about the study. 

Following treatment for endometrial cancer, patientswill be scheduled for follow-up visits every three to six months (per their physician’s instructions) for the first three years. Approximately 75 percent of recurrences are detected during this time. After three years, the likelihood of recurrence is reduced, and follow-up visits are typically scheduled semi-annually.

Ongoing research about endometrial cancer

A significant amount of research is being conducted in all areas of endometrial cancer. Scientists are studying molecular changes that can cause healthy endometrial cells to become cancerous. In addition, studies are examining the role of DNA in the risk of developing endometrial cancer. Inherited defects in certain genes may occur in families, increasing their risk for the disease. One normal gene, known as PTEN, is responsible for suppressing the growth of tumors in individuals. This gene often appears as abnormal in patients with endometrial cancer. Other DNA changes are being studied to help predict the aggressiveness of a cancer and to develop the best treatment methods for this type of disease.

Researchers are also studying tumor marker tests that may be used to help detect the presence of certain cancers. Recent studies indicate that the CA 125 blood test, a tumor marker test, may be useful in predicting the recurrence of endometrial cancer before tumors can be viewed on imaging tests. This test can be beneficial to physicians in planning treatment and monitoring patients for a recurrence of the disease.

Hormone replacement therapy (HRT) is also being studied by a research group known as the Women’s Health Initiative (WHI). The WHI receives funding from the National Institutes of Health to study women’s cancers. Among other studies, the WHI is investigating the association of HRT and women’s reproductive cancers.

Researchers continue to study new chemotherapy drugs or combinations of drugs in patients with endometrial cancer. Chemotherapy with or without radiation is also be evaluated for its effectiveness.

Staging endometrial cancer

The prognosis (predicted outlook or chance of survival) of endometrial cancer depends on the stage of the cancer. The stage indicates the extent of the cancer, or how widespread the disease is in the body. The staging system for endometrial cancer is called the FIGO (International Federation of Gynecology and Obstetrics) system. The FIGO system is a surgical system, which means that staging is based on the examination of surgically removed tissue. The FIGO system categorizes the cancer in stages I through IV, and divides some of the stages even further (e.g., stages IIA and IIB):

  • Stage I: The cancer is restricted to the body (corpus) of the uterus but may have spread through the myometrium (the muscular wall of the uterus).

  • Stage II: The cancer has spread to the cervix (the lower region of the uterus, located next to the vagina). It may be in the corpus, the endocervical glands (glands that form the inner lining of the cervix) or the cervical stroma (the connective tissue that supports the cervix).

  • Stage III: The cancer has extended outside or beyond the uterus, but is restricted to the pelvic area. It may have spread to surface tissue of the uterus or the tissues on the right and left side (such as the ovaries). Cancer cells may also be present in fluid from the lining of the abdomen and pelvis.

    • Stage IIIB: The cancer has reached the vagina, but has not affected lymph nodes or distant sites. Tumors may be of any size and may have spread to pelvic and/or paraaortic lymph nodes (lymph nodes around the uterus).
  • Stage IV: The cancer has reached the mucosa (inner surface) of the urinary bladder or the rectum (lower section of the large intestine), and/or has reached the lymph nodes in the groin, and/or has spread to distant organs, such as the lungs or bones.

According to the American Cancer Society (ACS), the 5-year survival rate of endometrial cancer by stage is as follows:

StageRate
Stage I81 to 91 percent
Stage II71 to 79 percent
Stage III52 to 60 percent
Stage IV15 to 17 percent
Overall84 percent

Questions for your doctor

Preparing questions in advance can help patients have more meaningful discussions with their physicians regarding their conditions. Patients may wish to ask their doctor the following endometrial cancer-related questions:

  1. Am I at risk for endometrial cancer?

  2. Which factors contribute to this risk?

  3. Should I use birth control pills to lower my risk?

  4. What type of hormone replacement therapy should I avoid?

  5. What tests will be performed to diagnose my cancer?

  6. Which biopsy procedure will be used?

  7. When and from whom will I receive my biopsy results?

  8. What is the stage of my endometrial cancer?

  9. What type of specialists will I need to see for this cancer?

  10. What are my treatment options for this cancer?

  11. What are the risks associated with these treatments?

  12. Is a complete hysterectomy my only surgical option?

  13. What is the prognosis with this type and stage of cancer?

  14. How will endometrial cancer and treatment affect my fertility?

  15. How will my condition be monitored after treatment?

  16. Are there ways to reduce my risk of this cancer?

  17. Are my daughters at greater risk for this cancer?

  18. Can you recommend a support group for me?
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