What is Endometrial Cancer?

Uterine cancer, also called endometrial cancer, is a cancer that originates in the endometrium, the inner lining of the uterus. (It is different from cancer of the uterine muscle, which is called uterine sarcoma.) The uterus is the hollow, pear-shaped organ where a fetus develops. It is located between a woman’s bladder and rectum.

What are the risk factors for endometrial cancer?

Most of the known risk factors for endometrial cancer appear to be related to changes in the balance between estrogen and progesterone, the two main female hormones. During a woman’s childbearing years, levels of each of these hormones shift on a monthly cycle, producing changes in the thickness of the endometrium.

When the menstrual cycle begins, the endometrium is very thin, consisting only of a few layers of cells. But for the first 14 days of a woman’s menstrual cycle, the ovaries produce more and more estrogen, which causes endometrial cells to proliferate (grow). This results in a thickening of the endometrium. Around day 14, ovulation occurs, and the ovaries begin to produce increasing levels of progesterone. At this stage, the cells of the endometrium become filled with glycogen, a complex sugar that will provide energy for a fertilized egg. If a fertilized egg is not implanted into the endometrium, the ovaries will stop producing progesterone after about two weeks. This sudden drop in progesterone levels causes the blood vessels that provide blood for the endometrium to contract. The endometrium then sloughs off, exiting the body as menstrual blood.

Understanding this cycle helps to show how a shift toward relatively more estrogen compared to progesterone can set the stage for uncontrolled endometrial cell growth, a precursor to cancer. In fact, any factor that increases the lifetime exposure of a woman’s endometrium to estrogen — for example, beginning menstruation early (before age 12) or going through menopause late (after age 52) – raises the risk of endometrial cancer. Because pregnancy shifts the hormonal balance toward more progesterone, women who have never been pregnant have a greater risk of developing cancer than women who have had children. Obesity also contributes to risk; women who are 50 pounds overweight have ten times the risk of endometrial cancer. The reason is that fat tissue can change certain hormones into estrogen, raising a woman’s total estrogen levels. Because both a diet high in animal fat and diabetes are associated with obesity, they are also considered risk factors for endometrial cancer.

Certain hormonal medications that affect estrogen levels influence the risk of endometrial cancer as well. Tamoxifen– a drug used to treat breast cancer or to lower the risk of developing breast cancer – is one example (though the benefit of the drug in treating breast cancer and in reducing the risk of cancer developing in the other breast far outweighs the risk of endometrial cancer).

The risk of endometrial cancer may also be affected by hormone replacement therapy, the use of female hormones after menopause to offset the sudden decline in estrogen production. Hormone replacement therapy is often prescribed for relieving menopausal symptoms such as hot flashes. Taking estrogen alone, however, has been shown to increase significantly a woman’s risk for developing endometrial cancer. Fortunately, this increase in risk can be erased by adding progesterone to estrogen replacement therapy. Estrogen is therefore almost never prescribed alone in menopausal women who still have a uterus.

As it is with all cancers, aging is also a risk factor for endometrial cancer; 95 percent of all cases occur in women over age 40, and the average age at diagnosis is 60. In addition, for unknown reasons, white women have a 70 percent greater risk for endometrial cancer compared with African Americans.

Other risk factors for endometrial cancer include a personal history of breast or ovarian cancer, or previous pelvic radiation therapy. A family history of endometrial cancer also raises the likelihood of developing the disease. A small number of cases may be due to the hereditary nonpolyposis colorectal cancer genetic abnormality, which, as the name implies, raises the risk of colorectal cancer as well. Women who carry this mutation are at higher risk for endometrial cancer.

Can anything be done to prevent endometrial cancer?

Because we do not know what exactly causes endometrial cancer, most cases cannot be prevented. However, there are several steps a woman can take that may help to reduce her risk of developing the disease.

First, the use of combination oral contraceptives by premenopausal women has been shown to decrease the risk of endometrial cancer. Controlling obesity and diabetes can also help. For a woman experiencing menopause and considering hormone replacement therapy, taking a combination of estrogen and progesterone, rather than estrogen alone, is essential if she still has her uterus. Finally, obtaining proper treatment for any precancerous disorders of the endometrium, such as endometrial hyperplasia (increased growth of endometrial cells), can stop the disease from developing. For example, a dilation and curettage (D & C, described below in “What tests are used to diagnose endometrial cancer?”) or a hysterectomy can prevent hyperplasia from turning cancerous. In some cases, taking progesterone medications can also control hyperplasia.

What are the symptoms of endometrial cancer?

The most common symptom of endometrial cancer is abnormal vaginal bleeding. In fact, about 90 percent of patients diagnosed with the disease have complained of irregular bleeding.

Other symptoms include abnormal vaginal discharge, difficult or painful urination, pain during intercourse, and pain in the pelvic area. These symptoms can be – and usually are – caused by conditions other than cancer. But it is important to visit a doctor to get a diagnosis.

What tests are used to diagnose endometrial cancer?

A routine screening test for endometrial cancer has not yet been developed. But if a doctor suspects that endometrial cancer may be causing a woman’s symptoms, he or she will conduct a thorough medical history and a physical exam, as well as one or several of the following diagnostic tests:

Pelvic exam: The doctor will check the vagina, uterus, cervix, ovaries, bladder, and rectum, feeling for any abnormalities such as lumps or changes in size.

Pap smear test: During the pelvic exam, the doctor will perform a Pap-smear test, in which he or she collects a sample of cells from the cervix and upper vagina. The sample is sent to a laboratory, where it is examined for abnormalities. However, because endometrial cancer originates inside the uterus, it may not show up on a Pap test.

Transvaginal ultrasound: The doctor inserts a probe into the vagina. The probe emits sound waves that echo off pelvic structures, projecting images of the uterus and its lining. The images can help the doctor detect the presence and size of a tumor.

Biopsy: The doctor uses one of several methods to remove a sample of tissue from the uterine lining for closer examination under a microscope. A biopsy is the only way to know for sure whether cancer is present.

In some cases, the biopsy will require a dilation and curettage (D&C). During a D&C, the cervix is widened, allowing entry to the uterus. The doctor scrapes a sample of tissue from the uterine lining. The tissue is then examined by a pathologist for cancer cells or other conditions.

If the biopsy reveals cancer, more tests will be done to find out how far the cancer has spread. This is called staging the cancer, and usually involves some blood and imaging tests. An example is a blood test for CA-125, a substance released into the bloodstream by many (not all) endometrial and ovarian cancers. Elevated levels of CA-125 suggest that the cancer has spread beyond the uterus.

Tests may also include a cystoscopy to check if the cancer has spread to the bladder; a proctoscopy to check if the cancer has spread to the rectum; and a chest x-ray to check the lungs for cancer.

What are the stages of endometrial cancer?

The stage of a cancer is the most significant factor when devising a treatment plan. The system used to stage endometrial cancer is called the FIGO (International Federation of Gynecology and Obstetrics) system. It classifies the cancer in stages I through IV and further divides some of the stages into A through C; for example, IA, IB, and IC. Below we provide the general definition of each stage, without detailing what differentiates letters A, B, and C. What you need to know is that the higher the stage number and letter, the more serious the condition.

Stage I: The cancer is limited to the body of the uterus.
Stage II: The cancer has spread from the body of the uterus to the cervix, which is the lowest part of the uterus. (The cervix marks the end of the vagina.)
Stage III: The cancer has spread beyond the uterus (to the vagina or the lymph nodes near the uterus, for example) but remains confined to the pelvic area.
Stage IV: The cancer has spread to the bladder or the rectum, and/or has spread to lymph nodes in the groin, and/or has spread to organs outside the pelvic area, such as the lungs.

How is endometrial cancer treated?

Treatment of endometrial cancer depends on the stage as well as a woman’s age, overall health, and desire to have children. Overall, treatment is very effective, with the five-year survival rate – the percent of patients who live at least five years after diagnosis – reaching 84 percent.

Surgery to remove the uterus (called a hysterectomy) and the fallopian tubes and ovaries (called a bilateral salpingo-oophorectomy) is the most common treatment for women with endometrial cancer. If the cancer has not spread beyond the endometrium, the disease can usually be cured with surgery alone.

The specific type of hysterectomy that a patient needs depends on the extent to which her cancer has spread:

Simple hysterectomy (also called a subtotal or supracervical hysterectomy) removes the upper portion of the uterus, leaving the cervix, fallopian tubes and ovaries intact.

Total hysterectomy removes the uterus and the cervix.

Total hysterectomy with salpingo-oophorectomy removes the uterus, cervix and either one (unilateral) or both (bilateral) ovaries and fallopian tubes. Radical hysterectomy removes the uterus, cervix, ovaries, fallopian tubes, nearby lymph nodes and tissue, and the upper part of the vagina. If the lymph nodes contain cancer cells, this means that the cancer may have spread to other parts of the body.

Radiation therapy, in which high-energy rays are used to kill cancer cells, may also be used to treat endometrial cancer, either before surgery to shrink the tumor or after surgery to destroy any remaining cancer cells.

There are two types of radiation therapy: external and internal. In external-beam radiation therapy, the radiation is administered from a machine, and the procedure is a lot like having an x-ray. Treatment requires four or five weeks of five-days-per-week therapy.

In internal radiation therapy, also called brachytherapy, tiny pellets containing a radioactive substance are inserted through the vagina. The procedure is usually performed about four to six weeks after a hysterectomy. Brachytherapy may require several treatments.

Hormone therapy involves the use of drugs such as progestins (synthetic progesterone) to thwart the growth of endometrial cancer cells by preventing them from using hormones they need to grow. The drugs are usually taken by mouth, then enter the bloodstream and travel throughout the body (called systemic therapy). Hormone therapy is used for treating women whose cancer has spread (metastasized) to distant sites (e.g., the lungs) and women with recurrent endometrial cancer.

Like hormone therapy, chemotherapy, the use of cancer-killing drugs, is a systemic treatment: It can kill cancer cells throughout the body. Typically, a combination of anticancer drugs are administered by vein (through an IV) or by mouth. Chemotherapy can be useful for women whose cancer has metastasized.