Endometrial cancer is one of the most common cancers in American women. In fact, about 40,000 American women receive a diagnosis of endometrial cancer each year, making it the fourth most common cancer found in women — after breast cancer, lung cancer and colon cancer.
Endometrial cancer usually begins in the lining of the uterus (endometrium). The uterus is a hollow, pear-shaped pelvic organ. Endometrial cancer most often occurs after the reproductive years, between the ages of 60 and 70. Endometrial cancer is sometimes called uterine cancer, but there are other cells in the uterus that can become cancerous — such as muscle or myometrial cells. These form much less common cancers called sarcomas and account for less than 5 percent of uterine cancers.
Endometrial cancer is often detected at an early stage because it frequently produces vaginal bleeding between menstrual periods or after menopause. If discovered early, this slow-growing cancer is likely to be confined to the uterus. Removing the uterus surgically often eliminates the cancer. In fact, stage I endometrial cancer is successfully treated more than 90 percent of the time. Unfortunately, not everyone can be successfully treated because the cancer may have spread beyond the uterus at the time of diagnosis. About 7,000 American women die each year of endometrial cancer.
Signs and symptoms
Endometrial cancer often develops over a period of years. Your first clue that something is wrong may be vaginal bleeding that’s uncommon for you.
Most cases of endometrial cancer develop in postmenopausal women, whose periods have stopped. However, a small percentage of cases affects women younger than 40. Signs and symptoms may include:
• Prolonged periods or bleeding between periods
• More frequent vaginal bleeding or spotting during the years leading up to menopause (perimenopause)
• Any bleeding after the time of menopause
• A pink, watery or white discharge from your vagina
• Pelvic pain, especially late in the disease
• Pain during intercourse
• Weight loss
Sometimes, but rarely, endometrial cancers can reach an advanced stage before signs and symptoms are present.
Causes
Healthy cells grow and divide in an orderly way to keep your body functioning normally. But sometimes this growth gets out of control — cells continue dividing even when new cells aren’t needed and create cancer.
In endometrial cancer, cancer cells develop in the lining of the uterus. Why these cancer cells develop isn’t entirely known. However, scientists believe that estrogen levels play a role in the development of endometrial cancer. Factors that can increase the levels of this hormone and other risk factors for the disease have been identified and continue to emerge. In addition, ongoing research is devoted to studying changes in certain genes that may cause the cells in the endometrium to become cancerous.
Risk factors
The female reproductive system consists of two ovaries, two fallopian tubes, a uterus and a vagina. The ovaries produce two main female hormones — estrogen and progesterone. The balance between these two hormones changes each month, helping the endometrium thicken in case pregnancy occurs or shed tissue if it doesn’t.
When the balance of these two hormones shifts toward more estrogen — which stimulates growth of the endometrium — a woman’s risk of developing endometrial cancer increases. Factors that increase levels of estrogen in the body include:
• Many years of menstruation. If you started menstruating at an early age — before age 12 — and continue to have monthly periods into your 50s, you’re at greater risk of endometrial cancer than is a woman who menstruated for fewer years. The more years you have had a monthly period, the more exposure your endometrium has had to estrogen.
• Never having been pregnant. The body produces more progesterone during a pregnancy, helping protect you from endometrial cancer by lowering levels of estrogen. If you’ve never been pregnant, you don’t get the benefit of this protection.
• Irregular ovulation. Ovulation, the monthly release of an egg from an ovary in menstruating women, is regulated by estrogen. Irregular ovulation or failure to ovulate can increase your lifetime exposure to estrogen. Ovulation irregularities have many causes, including obesity and a condition known as polycystic ovary syndrome (PCOS). This is a condition in which hormonal imbalances prevent ovulation and menstruation. Treating obesity and PCOS can help restore your monthly ovulation and menstruation cycle, decreasing your risk of endometrial cancer.
• Obesity. Ovaries aren’t the only source of estrogen. Fat tissue can change some hormones into estrogen. Being obese can increase levels of estrogen in your body, putting you at a higher risk of endometrial cancer and other cancers. A high-fat diet also can add to your risk by promoting obesity. Some scientists even think that fatty foods may directly affect estrogen metabolism, further increasing a woman’s risk of endometrial cancer.
• Diabetes. This is a risk factor for endometrial cancer mainly because obesity and type 2 diabetes often go hand in hand. However, some data suggest that women who have diabetes, whether they’re obese or not, are at greater risk of endometrial cancer.
• Estrogen-only replacement therapy (ERT). Estrogen stimulates growth of the endometrium. Replacing estrogen alone after menopause may increase your risk of endometrial cancer. Taking synthetic progestin, a form of the hormone progesterone, with estrogen — combination hormone replacement therapy — causes the lining of the uterus to shed and actually lowers your risk of endometrial cancer. However, this combination may cause other health risks.
• Ovarian tumors. Some tumors of the ovaries may themselves be a source of estrogen, increasing estrogen levels.
Other factors that can increase your risk of endometrial cancer include:
• Age. Most endometrial cancers develop over many years. Therefore, the older you are, the greater your risk. Ninety-five percent of endometrial cancer occurs in women older than 40.
• Personal history of breast cancer or ovarian cancer. Some of the same risk factors for breast cancer and ovarian cancer also increase your risk of endometrial cancer.
• Tamoxifen treatment. One in every 500 women whose breast cancer was treated with tamoxifen will also develop endometrial cancer. The drug acts like estrogen in some parts of the body, causing the uterine lining to grow. If you’re being treated with this hormone, see your doctor for an annual pelvic examination and be sure to report any unusual vaginal bleeding.
• Race. White women are more likely to develop endometrial cancer, but black women are much more likely to die of the disease.
• Hereditary nonpolyposis colorectal cancer (HNPCC). This inherited disease is caused by an abnormality in a gene important for DNA repair. Women with HNPCC also have a significantly higher risk of endometrial cancer.
Having risk factors for endometrial cancer doesn’t mean you’ll get the disease. It means that you’re at risk and should be alert to possible signs and symptoms of the disease. Conversely, some women who develop endometrial cancer appear to have no risk factors for the disease.
When to seek medical advice
Because endometrial cancer is more likely to be successfully treated the earlier it’s diagnosed, see your doctor if you experience any signs or symptoms of the disease — including vaginal bleeding or discharge not related to your periods, pelvic pain or pain during intercourse. Many of the symptoms you experience may be associated with noncancerous (benign) conditions, such as vaginal infections, uterine fibroids or uterine polyps. But it’s still important to bring them to the attention of your doctor.
Many endometrial cancers develop from less serious abnormalities of the endometrium that doctors can detect during routine exams and treat before they turn cancerous. That’s one of the reasons why regular gynecologic examinations are important for all adult women. This is especially true for women at high risk of endometrial cancer. If you’ve had endometrial cancer, ask your doctor about regular follow-up exams to check that the cancer hasn’t returned.
Screening and diagnosis
If your doctor suspects endometrial cancer, you may be referred to a gynecologist — a doctor who specializes in conditions affecting the female reproductive system. The gynecologist or your primary care doctor will conduct a complete medical history and perform a physical and pelvic examination. During the pelvic examination, the doctor feels for any lumps or changes in the shape of the uterus that may indicate a problem.
Diagnosis may or may not involve these other tests:
• Pap test. Your doctor takes a sample of cells from the cervix, the lower, narrower portion of the uterus that opens into your vagina. Doctors use the Pap test to detect another type of cancer — cervical cancer. Because endometrial cancer begins inside your uterus, it’s rarely detectable by a Pap test.
• Endometrial biopsy. To get a sample of cells from inside your uterus, you’ll likely undergo an endometrial biopsy. This involves your doctor removing a small piece of tissue from your uterine lining for laboratory analysis. This may be done in your physician’s office and usually doesn’t require anesthesia.
• Dilation and curettage (D and C). If enough tissue can’t be obtained during a biopsy or if the biopsy suggests cancer, you’ll likely need to undergo a D and C. In this procedure, which requires you to be in an operating room under anesthesia, tissue is scraped from the lining of your inner uterus and examined under a microscope for cancer cells.
• Transvaginal ultrasound. Your doctor may also recommend a transvaginal ultrasound to help rule out other conditions. In this painless procedure, a wand-like device (transducer) is inserted into your vagina. The transducer uses sound waves to create a video image of your uterus. This test helps your doctor look for abnormalities in your uterine lining.
If cancer of the endometrium is found, you’ll likely be referred to a gynecologic oncologist — a doctor who specializes in treating cancers involving the female reproductive system. You’ll need more tests to determine if the cancer has spread to other parts of your body (metastasis). These tests may include a chest X-ray, a computerized tomography (CT) scan and a blood test to measure cancer antigen 125 (CA 125), a substance that’s released in the bloodstream in some endometrial and ovarian cancers.
Once the diagnosis of endometrial cancer is confirmed, your doctor will want to “stage” your cancer. Staging is how doctors try to determine if the cancer has spread outside of the uterus. In endometrial cancer, staging is done through a surgical procedure and is done at the same time as any surgical treatment:
• Stage I cancer is found only in your uterus and hasn’t spread at all.
• Stage II cancer can be found in the body of both your uterus and your cervix. In this stage, cancer is no longer confined to the uterus, but hasn’t spread beyond the pelvic region.
• Stage III cancer has not involved the rectum and bladder, though pelvic area lymph nodes may be.
• Stage IV cancer is the most serious and means that the cancer has spread past the pelvic region and can affect the bladder, rectum and many other parts of your body.
Fortunately, about 75 percent of endometrial cancers are diagnosed at stage I or II.
Complications
When discovered early, endometrial cancer is usually treatable. However, in some women endometrial cancer reaches an advanced stage before diagnosis.
Endometrial cancer can cause pelvic pain and painful urination. As the cancer advances, symptoms may worsen. Treating the cancer can help alleviate the pain.
Women with endometrial cancer tend also to lose blood from vaginal bleeding. Over time, chronic loss of blood can result in anemia — a condition in which the blood is low on red blood cells and oxygen. Anemia causes fatigue and shortness of breath. But anemia can be treated along with your cancer, helping you regain energy.
Finally, endometrial cancer can recur in some women who don’t have their uterus removed during treatment.
Treatment
Surgery is the most common treatment for endometrial cancer. Most doctors recommend either the surgical removal of the uterus alone (hysterectomy) or, more likely, the surgical removal of the uterus, fallopian tubes and ovaries (complete hysterectomy). Lymph nodes in the area should also be removed during surgery along with other tissue samples during the staging operation. Lymph nodes are small, bean-shaped structures found throughout your body that produce and store infection-fighting cells, but may also be invaded by cancer cells.
A hysterectomy is a major operation, and because you can’t get pregnant after your uterus has been removed, it can be a difficult decision for some women. However, surgery is usually the only way to eliminate the cancer or the need for further treatment.
If you have an aggressive form of endometrial cancer or the cancer has spread to other parts of your body, you may need additional treatments. These may include:
• Radiation. Radiation therapy is the use of high-dose X-rays to kill cancer cells. If your doctor believes you’re at high risk of cancer recurrence, he or she may suggest that you have radiation therapy after a hysterectomy. Your doctor may also recommend radiation therapy if the cancerous tumor is fast growing, invades deeply into the muscle of the uterus or involves blood vessels. Brachytherapy is another form of radiation that involves the internal application of radiation, usually to the inner lining of the vagina. Brachytherapy has significantly fewer side effects than conventional radiation therapy does. However, brachytherapy treats only a small area of the body.
• Hormone therapy. If the cancer has spread to other parts of your body, synthetic progestin, a form of the hormone progesterone, may stop it from growing. The progestin used in treating endometrial cancer is administered in different doses from the progestin used in hormone replacement therapy for menopausal women. Some different medications may be used as well. Treatment with progestin may be an option for women with early endometrial cancer who want to have children and, therefore, don’t want to have a hysterectomy. However, this approach is not without the risk that the cancer will return. Carefully discuss this treatment with an expert in this field.
• Chemotherapy. Chemotherapy is the use of drugs to kill cancer cells. In some cases, your doctor may recommend chemotherapy for endometrial cancer. You may receive chemotherapy drugs by pill (orally) or through your veins (intravenously). These drugs enter your bloodstream and then travel through your body, killing cancer cells outside the uterus.
Each type of treatment for endometrial cancer can have side effects. Ask your doctor what side effects you can expect and what can be done to manage them.
If you have late-stage or recurrent endometrial cancer, you may be at decreased odds for successful treatment with standard therapies. You may benefit from participating in clinical trials that provide new experimental treatment options. For more information on clinical trials, contact the National Cancer Institute at (800) 4-CANCER, or (800) 422-6237, or visit its Web site.
After treatment for endometrial cancer, your doctor will likely recommend regular follow-up examinations to check that the cancer hasn’t returned. Checkups may include a physical exam, a pelvic exam, a Pap test, a chest X-ray and laboratory tests.
Prevention
Although most cases of endometrial cancer aren’t preventable, certain factors can lower your risk of developing the disease. These include:
• Taking hormone therapy (HT) with progestin. Estrogen stimulates growth of the endometrium. Replacing estrogen alone after menopause may increase your risk of endometrial cancer. Taking synthetic progestin, a form of the hormone progesterone, with estrogen causes the lining of the uterus to shed. This kind of combination hormone therapy lowers your risk. But not all effects of HT are positive. Taking HT as a combination therapy can result in serious side effects and health risks. Work with your doctor to evaluate the options and decide what’s best for you.
• A history of using birth control pills. Use of oral contraceptives can reduce endometrial cancer risk even as long as 10 years after you stop taking them. The risk is lowest in women who take oral contraceptives for many years.
• Maintaining a healthy weight. Obesity is one of the highest risk factors for the development of endometrial cancer in most women. You can help prevent endometrial cancer by maintaining a healthy weight. Excess fat tissue can increase levels of estrogen in your body, which increases your risk of endometrial cancer. Maintaining a healthy weight as you age lowers your risk of endometrial cancer as well as other diseases.
Self-care
Eating well, managing stress and exercising are ways to promote your overall health and cope with any form of cancer.
Eating well
Good nutrition is especially important for people undergoing cancer treatment. But eating well can be difficult if your treatment includes chemotherapy or radiation treatment. You may feel nauseated or lose your appetite, and foods may seem tasteless. You may find that the last thing you want to do is plan meals.
Even so, eating well during cancer treatment can help you maintain your stamina and your ability to cope with the side effects of treatments. Good nutrition may also help you prevent infections and remain more active.
Remember these strategies for eating well when you don’t feel well:
• Eat protein-rich foods. Foods high in protein can help build and repair body tissues. Eggs, yogurt, cottage cheese, peanut butter, beans, poultry and fish are good sources of protein.
• When you do feel well, make the most of it. Eat as many healthy foods as you can. Prepare meals that you can easily freeze and reheat. Also look for frozen dinners and other prepared foods.
• Pack calories into the foods you eat. For example, spread butter, jam or honey on bread. Sprinkle foods with chopped nuts.
• Eat smaller amounts of food more frequently. If you can’t face the thought of a large meal, try eating small amounts of food more often. Keep fruits and vegetables handy for snacking.
Managing stress
Methods for reducing physical tension can help you manage stress. One simple and powerful technique is to simply close your eyes and notice your breathing. Pay attention to each inhalation and exhalation. Your breathing will become slower and deeper, promoting relaxation. Another technique is to lie down, close your eyes and mentally scan your entire body for any points of tension.
Exercising
Activities such as running and swimming that require repetitive movements can produce a mental state similar to meditation. So can yoga and other stretching exercises.
Your doctor may have more specific suggestions about how to best care for yourself before, during and after treatment for endometrial cancer.
Coping skills
After you receive a diagnosis of endometrial cancer, you may have many questions, fears and concerns. How will the diagnosis impact you, your family, your work and your future? You may worry about tests, treatments, hospital stays and medical bills. Even if a full recovery is likely, you may worry about recurrence of your cancer.
Fortunately, many resources are available to you and your family to help answer questions and provide support. The key is to remember that you don’t have to face your questions or fears alone. Here are some strategies and resources that may make dealing with endometrial cancer easier:
• Know what to expect. Find out everything you can about your cancer — the type, stage, your treatment options and their side effects. It’s important for you to have honest, open discussions with your cancer care team. The more you know, the more active you can be in your own care. In addition to talking with your doctor, look for information in your local library and on the Internet. Staff of the National Cancer Institute will answer questions from the public. You can reach the cancer institute at (800) 4-CANCER, or (800) 422-6237. Or contact the American Cancer Society at (800) ACS-2345, or (800) 227-2345.
• Be proactive. Although you may feel tired and discouraged, don’t let others — including your family and your doctor — make important decisions for you. Take an active role in your treatment. Before starting treatment, you might also want to get a second opinion from a qualified specialist. Many insurance companies will pay for a second opinion.
• Maintain a strong support system. Strong relationships may help you cope with treatment and survive your cancer. Although friends and family can be your best allies, they sometimes may have trouble dealing with your illness. If so, the concern and understanding of a formal support group or other cancer survivors can be especially helpful. Ask your doctor to help you get in touch with a support group in your area.

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The uterus is the pelvic organ that holds the pregnancy and that bleeds each menstrual period. The cervix is that part of the uterus fixed at the top of the vagina. The normal size of the uterus is about that of a lemon. The uterus is divided into three parts. The great bulk of the uterus is composed of smooth muscle and forms a thick uterine wall. The inside of the uterus is lined with a glandular epithelium which is supported by the endometrial stroma. Together, the glandular lining and the endometrial stroma are referred to as the endometrium of the uterus. The endometrium is hormonally sensitive and changes throughout the menstrual cycle and during pregnancy.
TYPES OF UTERINE CANCERS
Each of these three parts gives rise to cancers. The smooth muscle cancers are called leiomyosarcomas(ly o myo sarcomas). There is also a benign tumor of smooth muscle called a leiomyoma. The common name for this benign tumor is myoma or fibroid. The endometrial stroma gives rise to a variety of cancers classified as sarcomas. The glandular lining gives rise to adenocarcinomas. Ninety-five percent, of uterine cancers are adenocarcinomas arising from the lining. The term uterine cancer usually refers to these adenocarcinomas.
Adenocarcinomas are graded. Grade I means well differentiated, that is, they are easily identified as originating from the glandular tissue and have easily identifiable glandular structures. Grade III means poorly differentiated with loss of the glandular structures. They are just solid cancer. Grade II cancers are intermediate in appearance. Grade I cancers are expected to behave the best, Grade III cancers the worst.
There are premalignant changes that can occur in the lining of the uterus. These changes are almost always due to excessive stimulation of the endometrial glands by an excess of estrogen or a prolonged estrogen influence. They can occur in younger women who do not ovulate regularly as well as in older women who are obese.
These changes are called endometrial hyperplasias. They are diagnosed usually by endometrial biopsy. They are not cancers but are often best treated by hysterectomy. They can also be treated by high dose progesterone therapy. If they occur in a young woman she will probably also be relatively infertile due to irregular or infrequent ovulation. In these cases, the treatment is by drugs that cause ovulation. If you ovulate you will no longer have unopposed estrogen stimulation because you now have the progesterone phase to the menstrual cycle. If you get pregnant then that will reverse the hyperplasia also. For most women the best treatment will probably be hysterectomy.
Papillary serous adenocarcinomas and clear cell adenocarcinomas are a subtype of uterine adenocarcinomas. They are different because of their increased potential to spread throughout the abdomen. In this they sometimes behave like an ovarian cancer. The diagnosis and staging is the same as for the more usual endometrial cancer. The best treatment has yet to be demonstrated. There is a good reason to consider treating the entire abdomen, but there is no good way to do it. Whole abdominal radiation can be done, but it can have a lot of side effects. This is a situation where several opinions should be obtained.
RISK FACTORS FOR UTERINE ADENOCARCINOMA
Age is the most important risk factor. This is a cancer of postmenopausal and perimenopausal women. There is also a well-recognized association with estrogen. Estrogen is a hormone produced by the ovary. The ovary does several things under the direction of the pituitary gland in the head. First, the pituitary directs the ovary to start maturing an egg. It does this by sending the ovary the pituitary hormone Follicle Stimulating Hormone (FSH). The ovary develops a small cyst or follicle about one half inch in size within which is the egg. During the maturation process the ovary is making estrogen. One of the effects of the estrogen is to stimulate the endometrial glands to grow and proliferate. Then the pituitary tells the ovary to ovulate which means break the follicle and release the egg. The pituitary hormone for this is called Luteinizing Hormone (LH).
The egg is ejected and floats into the fallopian tube. The remnant of the follicle, under the influence of LH starts to make progesterone. Progesterone converts the lining of the uterus to accept the pregnancy. If pregnancy does not occur that cycle then the ovary stops making progesterone. When the progesterone level falls the support for the uterine lining is lost and it falls off. This is the menstrual period. Then, it all starts over again: estrogen, ovulation, progesterone, and the period.
If the woman has a problem that prevents ovulation then the ovary will continue to make estrogen. This will result in prolonged unopposed estrogen stimulation to the endometrial glands and this will increase the risk for cancer of these glands. Postmenopausal women who are taking estrogen also will have an unopposed estrogen stimulation to the uterine glands and be at increased risk for developing an adenocarcinoma of the uterus. This is why a progestin such as Provera is also prescribed. Postmenopausal women who are obese have an increased level of estrogen because the adipose tissue converts other normal body chemicals into estrogen, so they are also at increased risk. Women who take Tamoxifen for breast cancer are also thought to be at increased risk because Tamoxifen is an estrogen. These increased risks are on the order of about 5-12 times the normal risk.
Conditions that increase the progesterone influence on the uterus decrease the risk for adenocarcinoma of the endometrium. Pregnancy is a time of increased progesterone levels, so women who have been pregnant most of their lives are at decreased risk. Women who have taken birth control pills for a long time are at decreased risk. Birth control pills contain both an estrogen and a progestin, but the net effect is that of the progestin. Prolonged progestin influence on the endometrium produces a thinning and atrophy of the glands which is just the opposite of the effects of estrogen. There are other minor risk factors but almost all are mediated through an estrogen progestin link.
SYMPTOMS OF UTERINE CANCER
The most frequent symptom of cancer of the uterus is abnormal bleeding. In postmenopausal women any bleeding is considered cancer of the uterus until proven not to be. The only way to prove that there is or is not a cancer inside the uterus is by removing some of the uterine lining as a biopsy. This can often be done easily in the office without any anesthesia, or it can be done in the operating room with an anesthetic. The procedure is called a D&C, dilatation of the cervix and curettage of the uterine lining. Sometimes a scope can be inserted through the cervix into the uterus and the lining visualized and biopsied directly. This is called hysteroscopy.
Whatever the procedure, you must be convinced that the bleeding is not due to a cancer inside the uterus. The Pap test cannot assess the inside of the uterus and is of no value. A trial of hormones is inappropriate. Any postmenopausal bleeding must be taken seriously and evaluated. Occasionally a sonogram or ultrasound test that assesses the thickness of the endometrial lining can be helpful, especially in an elderly debilitated woman who cannot be easily biopsied and who is also an anesthetic risk. If the lining can be seen and measures less than 5mm, then there is unlikely to be a cancer present.
The problem with postmenopausal hormone replacement is that it often causes some irregular bleeding which may require a biopsy. If the hormones are taken on a cyclic basis where there are several days each month when bleeding may occur and if the bleeding is light and occurs on those days then biopsy need not be done. If it occurs at any other time in the cycle then a biopsy should be done. If the hormones are both being taken on a continuous basis each day and bleeding occurs then a biopsy should be performed
SCREENING FOR UTERINE CANCER
There are no recommendations for screening for cancers of the uterus. The only screening procedure is an endometrial biopsy. Some have suggested that women who are taking replacement estrogen only, without the progesterone, should have an annual biopsy. Also women on Tamoxifen should probably be biopsied annually. The Pap test is inadequate for cancers inside the uterus although occasionally this cancer will be found on a Pap test. If the Pap test shows endometrial cells then this is abnormal and should be evaluated with an endometrial biopsy.
DIAGNOSIS
Cancers of the uterus are diagnosed by endometrial biopsy, D&C, hysteroscopy and sometimes only after hysterectomy. The important point is that any postmenopausal bleeding must be considered a cancer of the uterus until proven otherwise. It is fortunate that uterine cancers bleed early so symptoms are early and if the bleeding is not ignored, diagnosis is early. Three-fourths of all uterine cancers are diagnosed at an early stage. Of these about three-fourths are of favorable grade. This is why the number of deaths from uterine cancer is low even though it is the most frequently diagnosed gynecologic cancer.
STAGING OF UTERINE CANCER
Cancers of the uterus are staged by surgical exploration with removal of the uterus, tubes and ovaries. In addition, an assessment of the pelvic and aortic lymph nodes is done.
SURGICAL STAGES OF CANCER OF THE UTERUS

Stage I Cancer limited to the lining of the uterus
IA No invasion into the uterine wall
IB Invasion into less than one half of the uterine wall
IC Invasion into more than one half the uterine wall

Stage II Extends into the cervix
IIA Extends only superficially along the endocervix
IIB Extends deep into the cervix

Stage III Cancer has spread beyond the uterus
IIIA Cancer involves the tubes or ovaries
IIIB Spread to the vagina
IIIC Spread to the pelvic or aortic lymph nodes

Stage IV Distant metastases
IVA Is inside the bladder or rectum
IVB Throughout the abdomen or other distant sites
In addition, these cancers are also graded; Grade I, II and III. To determine the correct stage the uterus, tubes and ovaries will have to be removed as well as sampling the pelvic and aortic lymph nodes. An early stage is assigned by excluding the more advanced stage. Some cases that are obviously in an advanced stage by physical examination will not benefit from surgery and can be treated without operative staging.
TREATMENT
Treatment of uterine cancers is usually by a combination of surgery and radiation. Those that are at an early stage will be operated first with removal of the uterus, tubes and ovaries, to confirm the stage. If there is only limited invasion into the wall of the uterus and the grade is good, i.e. grade I or II, then the surgery will be sufficient and no radiation will be recommended. If of higher stage and grade then radiation to the pelvis will often be advised. Some doctors prefer to give radiation prior to surgery but that is becoming less prevalent. Advanced stages are treated by radiation if possible, or chemotherapy. Fortunately, progesterone, which has few side effects, is a good chemotherapeutic. Other types of chemotherapy have limited effectiveness but are often used and can give an initially good response.
Most patients will be in an early stage when diagnosed and there will be several options for treatment. Often these are elderly women who may have other medical problems. Nevertheless, a maximum effort should be taken to bring these patients to surgery since the cure rate drops by 20% if a hysterectomy is not performed. With no other gynecologic cancer is treatment so individualized as with early stage endometrial cancer.
PROGNOSIS
Since most patients are diagnosed at an early stage and with an optimal grade, most patients are cured. Nevertheless, stage for stage it is just as bad a cancer as any other. Most recurrences will occur in the first two years. If none have occurred by five years the patient is considered cured.
FIVE YEAR SURVIVAL FOR UTERINE ADENOCARCINOMA

Stage I 80%
Stage II 65%
Stage III 30%
Stage IV 10%
Stage IA, grade I, cancers have a five year survival in excess of 95%. The prognosis depends on the substage and the grade.
ODDS AND ENDS
Adenocarcinomas of the endometrium are often hormonally sensitive cancers and occasionally estrogen and progesterone receptors will be determined, but this is not commonly done.
There are several different cell types included in the designation adenocarcinoma. Some trend to behave in a more virulent manner but all are treated about the same.
The Ca-125 blood test is often elevated in endometrial adenocarcinomas, and if so, can serve as a tumor marker.
Endometriosis is a benign condition in which endometrial tissue (glands and stroma) is misplaced onto other structures. Often there are implants on the surface of the outside of the uterus or on the lining of the pelvis. They can even occur inside the ovary. Each time the lining of the uterus bleeds during menses these implants also bleed and can cause pain and adhesions. If inside the ovary it can cause a blood filled ovarian cyst called an endometrioma. Endometriosis is a benign condition but one that can cause a lot of problems. Very rarely an endometrial adenocarcinoma can arise in an endometrial implant.
NEVER, NEVER IGNORE POSTMENOPAUSAL BLEEDING, AND DO NOT LET YOUR DOCTOR IGNORE IT EITHER. YOU MUST PROVE THAT IT IS NOT DUE TO A UTERINE CANCER.
UTERINE SARCOMAS
Uterine sarcomas are rare cancers and are not easy to generalize. There are several types each with several gradations from low grade to high grade malignancies. There is no standard treatment. Each case must be managed separately.
The thick muscular wall of the uterus gives rise to the benign leiomyoma and the malignant leiomyosarcoma. The benign leiomyoma is also called a fibroid tumor. They are common and often require no treatment. They are often diagnosed by physical examination when the examiner feels an enlarged lumpy, bumpy uterus. It is only a guess that they are fibroids but usually a very good guess. An ultrasound test can also indicate a possible fibroid. Fibroids can become very large and then should be removed. Often there are multiple fibroids and occasionally these can be removed and the uterus preserved. Fibroids should diminish in size after the menopause. Therefore, any enlarged uterus in a postmenopausal woman not known previously to have fibroids should be removed because it could be a leiomyosarcoma. An enlarging fibroid in a premenopausal woman should also be removed. If there is no need for future pregnancies then the whole uterus should be removed.
Leiomyosarcomas are graded by the number of cells undergoing cell division. If few dividing cells are noted then it may be a low grade cancer or not a cancer at all. If a high number are noted ,i.e. a high mitotic count, then this will be a very aggressive cancer. Even stage I leiomyosarcomas, if high grade, will be very aggressive and most will recur. Unfortunately, there is no convincing scientific proof that either radiation or chemotherapy can prevent a recurrence from happening.
The endometrial stroma gives rise to a variety of sarcomas, some low grade and some very high grade. There are even benign conditions that can metastasize through the veins. There is no way to generalize about uterine sarcomas. Each specific type and its grade will have to be individually considered.
William M. Rich, M.D.
Clinical Professor of Obstetrics and Gynecology
University of California, San Francisco
Director of Gynecologic Oncology
University Medical Center

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This topic provides information about cancer of the lining of the uterus (endometrium). This topic focuses on type I endometrial cancer, which is the most common kind.
If you are looking for information about cancer of the cervix, see the topic Cervical Cancer.
What is endometrial cancer?
Endometrial cancer is the growth of abnormal cells in the lining of the uterus. The lining is called the endometrium. Endometrial cancer is also called cancer of the uterus, or uterine cancer.
Endometrial cancer usually occurs in women older than 50. The good news is that it is usually cured when it is found early. And most of the time, the cancer is found in its earliest stage, before it has spread outside the uterus.
What causes endometrial cancer?
The most common cause of endometrial cancer is having too much of the hormone estrogen compared to the hormone progesterone in the body. This hormone imbalance causes the lining of the uterus to get thicker and thicker. If the lining builds up and stays that way, then cancer cells can start to grow.
Women who have this hormone imbalance over time may be more likely to get endometrial cancer after age 50. This hormone imbalance can happen if a woman:
What are the symptoms?
The most common symptom of endometrial cancer is unexpected (abnormal) bleeding from the vagina after menopause. (If you are taking hormone therapy, some vaginal bleeding is expected.) About 20 out of 100 women who have abnormal bleeding after menopause have endometrial cancer.1 That means that 80 out of 100 women with abnormal bleeding don’t have this cancer.
A woman with advanced endometrial cancer may have other symptoms, such as losing weight without trying.
How is endometrial cancer diagnosed?
Endometrial cancer is usually diagnosed with a biopsy. In this test, the doctor removes a small sample of the lining of the uterus to look for cancer cells.
How is it treated?
Endometrial cancer in its early stages can be cured. The main treatment is surgery to remove the uterus plus the cervix, ovaries, and fallopian tubes. If the cancer has spread, the doctor may also remove the pelvic lymph nodes.
A woman whose cancer has spread may also have:
It’s common to feel scared, sad, or angry after finding out that you have endometrial cancer. Talking to others who have had the disease may help you feel better. Ask your doctor about support groups in your area. You can also find people online who will share their experiences with you.

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Endometrial cancer is the fourth most common cancer in women, accounting for approximately 6,000 deaths per year in the United States. It is more common in women who are older, white, affluent, obese and of low parity. Hypertension and diabetes mellitus are also predisposing factors. Because any condition that increases exposure to unopposed estrogen increases the risk of endometrial cancer, tamoxifen therapy, estrogen replacement therapy without progestin and the presence of estrogen-secreting tumors are all risk factors. Smoking and the use of oral contraceptives appear to decrease the risk. Women with an increased risk and those with postmenopausal bleeding should be screened for endometrial cancer. Endometrial sampling is currently the most accurate and widely used screening technique, but ultrasonographic measurement of endometrial thickness and hysteroscopy have also been studied. Patients with endometrial specimens that show atypia have about a 25 percent likelihood of progressing to carcinoma, compared with less than 2 percent in patients without atypia. Endometrial cancer is usually treated surgically, but in patients with appropriate pathologic findings who decline surgical treatment, progestin therapy may be satisfactory.
Uterine cancer, the most common malignant neoplasm of the female genital tract and the fourth most common cancer in women, is currently diagnosed in about 34,000 women each year. In 1997, about 6,000 women in the United States died of this disease.1 It is more frequent in affluent and white women, especially obese, postmenopausal women of low parity.2 Hypertension and diabetes mellitus are also predisposing factors.3 Uterine cancer is most frequently diagnosed in industrialized western nations, with the lowest rates occurring in India and Southeast Asia.2
Advances in the past two decades have expanded our knowledge of endometrial cancer, giving us a better definition of the histologic subtypes and providing us with better screening and surgical tools with which to diagnose and treat this disease.2
Pathogenesis
It was originally hypothesized that endometrial hyperplasia represented a morphologic continuum from benign cystic hyperplasia to atypical complex hyperplasia, which may be the immediate precursor of endometrial carcinoma.2 Several recent studies have suggested that endometrial hyperplasia and endometrial cancer are two different entities, and the distinguishing feature is the presence or absence of cytologic atypia.2 Studies have shown that patients who have endometrial hyperplasia without atypia respond well to progestin therapy and are not at increased risk for cancer; however, patients with cytologic atypia show only a 50 percent response to progestin therapy, and cancer develops in 25 percent of cases.4-6
Uterine cancer is a general term used to describe many different histopathologic types of tumors found in the uterus. The most common cancer of the uterus is adenocarcinoma. Several other histologic subtypes also occur (Table 1). The less common forms are associated with a lower overall survival rate and a higher risk of metastatic disease at the time of surgical staging.2 Patients with serous (also known as papillary serous) and clear cell carcinomas tend to be older than those with other types (mean age: 66 versus 59 years) and are more likely to have abnormal cervical cytology.7 Serous carcinoma invades the myometrium and lymph-vascular spaces early and has been shown to metastasize without deep myometrial invasion.2
Risk Factors
Any characteristic that increases exposure to unopposed estrogen increases the risk for endometrial cancer (Table 2).2,4-8 Conversely, decreasing exposure to estrogen limits the risk. Unopposed estrogen therapy, obesity, anovulatory cycles and estrogen-secreting neoplasms all increase the amount of unopposed estrogen and thereby increase the risk for endometrial cancer. Smoking seems to decrease estrogen exposure, thereby decreasing the cancer risk, and oral contraceptive use increases progestin levels, thus providing protection.9 Tamoxifen (Nolvadex) therapy, often used in women with breast cancer, has an estrogenic effect on the female genital tract and, through this unopposed estrogen exposure, increases the risk for endometrial cancer.10 Physicians should be aware that endometrial ablation is not a treatment for endometrial hyperplasia or carcinoma, and a previous ablation does not protect against the development of endometrial disease.
Hormone Replacement Therapy
Unopposed estrogen treatment of menopause is associated with an eightfold increased incidence of endometrial cancer.11,12 The addition of progestin decreases this risk dramatically.12 For maximum endometrial protection, administration of medroxyprogesterone acetate (Provera), in a dosage of 10 mg daily, or norethindrone acetate (Aygestin), in a dosage of 2.5 mg daily, for a minimum of 12 to 14 days per month has been recommended.13 However, some physicians prescribe lower dosages, either 5.0 or 2.5 mg of medroxyprogesterone daily.
A 13-day “progestin challenge” course of either 10 mg of medroxyprogesterone or 2.5 to 5 mg of norethindrone given to postmenopausal women resulted in withdrawal bleeding and correlated with a high likelihood of endometrial pathology.13 In this study, it was found that low dosages may not provide maximal endometrial protection.13 However, the Postmenopausal Estrogen/Progestin Interventions (PEPI) trial14 found no difference in the risk for endometrial disease between patients taking placebo and those taking estrogen with medroxyprogesterone, in a dosage of either 10 mg per day for 12 days or 2.5 mg per day continuously.
One possible explanation for these contradictions can be found in the patient groups studied. Many of the patients in one study had one or more risk factors for endometrial disease,13 whereas the PEPI trial involved a randomly selected cohort.14 These findings suggest that patients at high risk for endometrial disease should receive higher dosages of progestins than patients at low risk, a suggestion that is supported, in theory, by the pathophysiology. Further studies may be necessary for more definitive recommendations

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Treatment
After diagnosis and initial evaluation, the doctor considers treatment options that fit each woman’s needs and discusses these options with her. The choice of treatment depends on the size of the tumor, the stage of the disease, whether female hormones affect tumor growth, and tumor grade. (The tumor grade tells how closely the cancer resembles normal cells and suggests how fast the cancer is likely to grow. Low-grade cancers are likely to grow and spread more slowly than high-grade cancers.) Other factors, including the woman’s age and general health, are also considered when planning treatment. Women with uterine cancer may be treated by a team of specialists that may include a gynecologist, gynecologic oncologist (a doctor who specializes in treating cancer of the female reproductive tract), and a radiation oncologist.
Getting a Second Opinion
Before starting treatment, a woman may want a second specialist to confirm the diagnosis and review her treatment options. It may take a week or two to arrange for another opinion, but a short delay will not reduce the chance that treatment will be successful. Some insurance companies require a second opinion; many others cover a second opinion if the patient requests it. There are a number of ways to find a doctor who can give a second opinion:
• The woman’s doctor may be able to suggest specialists to consult.
• The Cancer Information Service, at 1-800-4-CANCER, can tell callers about treatment facilities, including cancer centers and other programs supported by the National Cancer Institute.
• A woman can get the names of doctors from her local medical society, a nearby hospital, or a medical school.
• The Official ABMS Directory of Board Certified Medical Specialists lists doctors’ names along with their specialty and their background. This resource is in most public libraries.

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Endometrial cancer - carcinoma of the lining of the uterus - is the most common gynecologic malignancy in women.
Description of Uterine Cancer
Endometrial carcinomas arise from the glands of the lining of the uterus, the pear-shaped organ in the pelvis. Cervical cancer and ovarian cancer are other types of gynecologic cancers in women.
Adenocarcinoma accounts for about 75 percent of all endometrial carcinomas. It occurs most often in women 50 to 70 years of age.
Endometrial adenocarcinomas that contain benign squamous cells are known as adenoacanthomas and account for about 17 percent of endometrial cancer.
The remaining three types of endometrial carcinoma have a poor prognosis. Approximately 15 percent of woman have adenosquamous carcinoma, in which both the gland cells and squamous cells are malignant.
Three percent have a clear cell carcinoma, and about one percent have a papillary carcinoma. Uterine sarcoma is another kind of uterine malignancy.
From where it arises in the lining of the uterus, untreated endometrial carcinoma eventually invades the wall of the uterus and may involve the cervix. With time, it can grow through the wall of the uterus into the surrounding tissues (the parametrium), the bladder and the rectum.
It also can spread by the lymphatic system to the vagina, fallopian tubes, ovaries, the pelvic and aortic lymph nodes and to the lymph nodes in the groin and above the collarbone (supraclavicular).

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Introduction
The uterus (womb) is part of the female reproductive system and is located at the top of the vagina. It is where a baby grows during pregnancy.
The lining of the uterus is called the endometrium and is shed each month as part of your period. Most cancers of the uterus develop in the lining are called endometrial cancer. Cancer of the uterus can also be called uterine cancer.
Endometrial cancer is fairly common; about 5,000 - 6,000 women a year are affected (1). It mostly affects women between the ages of 50 and 70, who have been through the menopause (when your periods stop). It is more common in women who have never been pregnant. Like all cancers, it is important to get early treatment so that the cancer does not spread to other parts of the body.
About 95% of endometrial cancers of the uterus are adenocarcinomas. Cancers that start in the muscle of the womb (sarcomas) are even less common. There are three types of adenocarcinomas. The most common (over 75% of cases) is endometriod adenocarcinoma. The other types are papillary serous carcimona (5%), clear cell carcinoma (very rare), and leiomyosarcoma (rare).
The neck of the uterus is called the cervix. You can find more information about cancer of the cervix (cervical cancer) in the separate topic.

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Cancer of the endometrium, or lining of the uterus (sometimes called the womb), is called endometrial cancer. The most common sign of endometrial cancer is unusual bleeding from your vagina, especially bleeding after menopause.

Endometrial cancer can almost always be treated successfully if it’s caught early. You can increase the chances that endometrial cancer will be found early by telling your doctor about any unusual bleeding.
Am I at risk for endometrial cancer?
Certain things may put you at greater risk for getting endometrial cancer. One risk factor is age. Endometrial cancer is most common in women who are over 50 years of age.

You may also be at greater risk if you have had high levels of estrogen in your body. Many things can increase your estrogen level. These include being extremely overweight, having high blood pressure or having diabetes.

Using estrogen replacement therapy without taking progestin may also increase the risk for endometrial cancer. For this reason, women who use hormone replacement therapy (HRT) generally take a combination of estrogen and the hormone progestin. Progestin seems to protect the lining of the uterus from the estrogen. In fact, using birth control pills that contain both estrogen and progestin during the childbearing years seems to decrease a woman’s risk of endometrial cancer.

Other things that may put you at greater risk for endometrial cancer include having your first period before the age of 12 or going through menopause after the age of 50. Women who have never been pregnant and women who use a medicine called tamoxifen may also be at greater risk.

How is endometrial cancer diagnosed?
Your doctor will diagnose endometrial cancer by performing one or more of the following procedures:
• Endometrial biopsy is usually done in your doctor’s office. It involves inserting a narrow tube into the uterus through the vagina and removing a small amount of tissue from the uterine wall. This tissue is tested in a lab for cancerous or precancerous cells. The procedure usually takes just a few minutes.
• Dilatation and curettage (D & C) involves dilating (widening) the cervix (the opening of the uterus) and inserting an instrument to scrape or suction the uterine wall and collect tissue. D & C is also an outpatient procedure. It takes about an hour and usually requires general anesthesia (puts you in a sleep-like state).
• Imaging tests are used in patients with certain medical conditions such as severe high blood pressure, obesity, diabetes, or other types of cancer. These patients may not be able to safely have anesthesia. In these patients, imaging tests such as an MRI scan, CT scan, or ultrasound may help diagnose cancer of the uterus.
Your doctor will talk to you about which procedure is right for you.
What is the treatment for endometrial cancer?
Treatment usually involves removing the uterus, the fallopian tubes and the ovaries. You may also need to take progestin to balance out high levels of estrogen. Sometimes radiation therapy or chemotherapy is also needed. Treatment can be very effective, especially if the cancer is found early.

Cancer
• Common Cancers in Adults
• Melanoma
• Multiple Myeloma
• Nasopharyngeal Cancer
• Osteosarcoma in Children and Teenagers
• Prostate Cancer
• Testicular Cancer
• Vulvar Cancer
• Stomach Cancer
Other Organizations
• American Cancer Society
800-ACS-2345 (800-227-2345)
• American Cancer Society: Support Programs and Services
• National Cancer Institute
800-4-CANCER
• Revolution Health Cancer Community

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Endometrial cancers develop in the uterus, though most develop in the endometrial glands that line the inner wall of the uterine cavity rather than in the uterus’ muscular wall.
Although endometrial cancer usually occurs after menopause, it also may occur around the time that menopause begins. Abnormal vaginal bleeding is the most common symptom of uterine cancer. Bleeding may start as a watery, blood-streaked flow that gradually contains more blood. Women should not assume that abnormal vaginal bleeding is part of menopause.
You should see your doctor if you have any of the following symptoms:
• Unusual vaginal bleeding or discharge
• Difficult or painful urination
• Pain during intercourse
• Pain in the pelvic area

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By far, the most common symptom of endometrial carcinoma is abnormal bleeding from the vagina.
In women who have been through menopause, any vaginal bleeding is abnormal and should be evaluated by a doctor.
In women who have not been through menopause or who are currently going through menopause, distinguishing normal menstrual bleeding from abnormal bleeding may be difficult. A heavier or more frequent period or bleeding between periods is sometimes linked to cancer in menstruating women. During the transient period of going through menopause, the menstrual period should become shorter and shorter and the frequency should become farther apart. Any other bleeding should be reported to a doctor.
The following symptoms are much less common and usually indicate fairly advanced cancer:
Pelvic pain
Mass (swelling or lump) in the pelvic area
Weight loss

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