What is endometrial cancer?

Related conditions:
Obesity, hypertension, polycystic ovary syndrome, endometrial hyperplasia

Definition:

Endometrial cancer is cancer of the endometrial cells that line the uterus, which is the female organ in which the fetus develops. Estrogen, a female hormone, is a primary growth signal for the endometrium (lining of the uterus). When endometrial cells are exposed to increased levels of estrogen for long periods of time and when they acquire certain genetic mutations, they can become cancerous.

Risk factors: Certain demographic characteristics including being over the age of fifty, being white, and never having been pregnant can contribute to the risk of endometrial cancer. Long-term exposure to estrogen may also affect the incidence of endometrial cancer. Estrogen exposure can be in the form of hormone replacement therapy (commonly used to control menopause-related symptoms) or tamoxifen (an estrogen-like drug used to prevent or treat breast cancer). Increased exposure to estrogen can also occur in women who began menstruation early (before the age of twelve) or reached menopause late (after the age of fifty). Because estrogen can be produced in fatty tissue, being overweight can increase the risk of endometrial cancer. Furthermore, obesity-related conditions, such as type 2 diabetes and high blood pressure, may increase the risk. Finally, many diseases may also be associated with an elevated risk of endometrial cancer, including endometrial hyperplasia (a noncancerous condition characterized by overgrowth of the endometrium), a history of breast or ovarian cancer, and hereditary nonpolyposis colorectal cancer (a disease caused by mutations in deoxyribonucleic acid, or DNA, repair genes).

Etiology and the disease process: Within the female reproductive system, the ovaries are responsible for producing the hormones estrogen and progesterone. The levels of these hormones fluctuate each month, allowing the endometrium to thicken (because of endometrial cell growth) at the beginning of the monthly menstruation cycle in preparation for an egg to be fertilized and implanted within the uterus. At the end of the monthly cycle, the endometrium is shed if pregnancy does not occur. Because estrogen is responsible for stimulating the growth of endometrial cells, too much estrogen may lead to too much cell growth.

Genetic changes may also contribute to the transformation of normal cells into cancerous cells. Endometrial cancer can be divided into type 1 and type 2 carcinomas based on their relationship with estrogen and how the cells look under a microscope. Type 1 carcinoma, which accounts for 70 to 80 percent of all endometrial cancer cases, is estrogen dependent and associated with the inactivation of PTEN (a tumor-suppressor gene) and mutations in DNA repair genes, KRAS (a gene that encodes a proto-oncogene), and beta-catenin (a protein). In the less prevalent (but more aggressive) type 2 carcinoma, which follows an estrogen-independent pathway, major genetic changes within endometrial cells include mutations in TP53 (another tumor-suppressor gene) and overexpression of human epidermal growth factor receptor 2/neu (HER2/neu). When cells have tumor-suppressor genes and DNA repair genes that are not functional, they lose the ability to regulate growth and cell division, as well as the ability to fix additional mutations that may arise. Expressing excess growth factor receptors also means that cells may grow and divide more quickly and may not respond when cellular signals try to stop proliferation.

Incidence: In women, endometrial cancer is the fourth most common cancer (after breast, lung, and colon cancers). Some 95 percent of uterine cancers are endometrial; the other 5 percent are due to cancerous muscle or myometrial cells within the uterus. The American Cancer Society estimated that there were 52,630 new cases of uterine cancer and 8590 deaths from the disease in the United States, though approximately 2 percent of these cases are other forms of uterine cancer.

Symptoms: The most common symptoms in endometrial cancer are pelvic pain and vaginal bleeding between menstrual periods or after menopause.

Screening and diagnosis: Screening tests such as a pelvic exam, a Pap smear (to check for cervical cancer), and a transvaginal ultrasound (to determine if the endometrium is too thick) may be performed. Blood tests can look for lower red blood cell counts (possibly indicating loss of blood from the uterus) and for raised levels of cancer antigen 125 (CA 125, a protein that is associated with tumors of the endometrium and ovaries).

To make a diagnosis, a tissue sample from the uterine lining should be removed and analyzed under the microscope. Tissue samples can be obtained either by a biopsy or by dilation and curettage (D&C). A D&C is a more invasive procedure for obtaining endometrial tissue and may be done if the biopsy did not obtain a large enough sample or if the biopsy was positive for cancer and a confirmation is needed.

Endometrial cancer is staged using the International Federation of Gynecology and Obstetrics (FIGO) cancer staging system, as follows:

• Stage I: The tumor is only in the uterus.





• Stage II: The cancer has spread from the body of the uterus to the cervix.





• Stage III: The cancer has spread outside the uterus but not outside the pelvis (and not to the bladder or rectum). Lymph nodes in the pelvis may contain cancer cells.





• Stage IV: The cancer has spread into the bladder or rectum, or it has spread beyond the pelvis to other parts of the body.

Treatment and therapy: Women with endometrial cancer may undergo surgical removal of the uterus, in a procedure known as a hysterectomy. Often, the uterus is removed along with the Fallopian tubes and ovaries as well as neighboring lymph nodes to ensure that all of the cancerous cells have been removed. Although this is the standard treatment for women already in menopause and no longer fertile, women of childbearing age need to consider the outcome of this surgery as they will lose the ability to have a child. For Stage I endometrial cancer, surgery to remove the uterus has been shown to be 90 percent effective.

Radiation therapy, where high-dose X rays are used to kill cancer cells, may be used after surgery to prevent the formation of or treat existing cancer cells outside the uterus. Radiation may also be used in place of surgery if women refuse a hysterectomy or if a tumor is growing rapidly, associated closely with muscle cells in the uterus, or is highly vascularized (with lots of blood vessels infiltrating the tumor). Radiation therapy can be delivered either conventionally (the standard external X ray) or as brachytherapy (internal radiation to target only the inner lining of the uterus). Although brachytherapy has fewer side effects than conventional radiation therapy, its effects are only local, so it cannot be used if the cancer has spread outside the uterus.

Hormone therapy is often used when cancer has spread outside the uterus. Synthetic progestin, which is a form of progesterone, is used to inhibit the growth of cancerous endometrial cells. Although this therapy may be associated with higher risks of recurrence than surgical removal of the uterus, this option is attractive to women who still want to have children or who were diagnosed in a very early stage. Chemotherapy may also be used to kill cancer cells that have spread beyond the uterus.

Prognosis, prevention, and outcomes: To prevent endometrial cancer (both initial and recurrent cases), taking hormones with progesterone may help slow or inhibit the growth of endometrial cells. Women may undergo hormone therapy with progestin or take birth control pills. Women who take birth control pills have a reduced risk of endometrial cancer for up to ten years after discontinuing oral contraceptives. As with other cancers, living a healthy lifestyle is important in reducing the risk of cancer. This includes maintaining a healthy weight (as obesity is a risk factor for developing endometrial cancer) and exercising regularly.

For endometrial cancer, the five-year survival rates for women receiving the proper treatment are approximately 75 to 95 percent for women diagnosed at Stage I, 50 percent for Stage II, 30 percent for Stage III, and less than 5 percent for Stage IV.

In a study analyzing recurrence rates across sixteen studies, the overall risk of recurrence was 13 percent, and this was even less in low-risk patients who were diagnosed with Stage I or II cancers or who did not have associated diseases known to increase the risk of endometrial cancer. This study also showed that about 70 percent of recurrences were accompanied by symptoms, and 68 to 100 percent of these recurrences occurred within about a three-year span after the follow-up visit.

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