Endometrial cancer

ALSO KNOWN AS: Uterine corpus cancer, uterine 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 endometriumuterus lining. When endometrial cells are exposed to increased levels of estrogen for long periods and when they acquire specific 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 therapyused 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 earlybefore the age of twelveor reached menopause lateafter 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 cancera 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 thickenendometrial cell growthat the beginning of the monthly menstruation cycle in preparation for an egg to be fertilized and implanted within the uterus. The endometrium is shed at the end of the monthly cycle if pregnancy does not occur. Since 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, significant 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 and fix additional mutations that may arise. Expressing excess growth factor receptors also means that cells may grow and divide more quickly and not respond when cellular signals try to stop proliferation.

Incidence: By 2018, endometrial cancer was the tenth most common cancer. The American Cancer Society (ACS) estimated that for 2024 there would be 67,880 new cases of uterine cancer and 13,250 deaths from the disease in the United States, though approximately 10 percent of uterine cancers are sarcomas affecting the myometrial (muscle) cells within the uterus.

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

Screening and diagnosis: Medical professonals may perform screening tests such as pelvic exam, Pap smears to check for cervical cancer, and transvaginal ultrasounds to determine if the endometrium is too thick. Blood tests can look for lower red blood cell countspossibly indicating loss of blood from the uterusand raised levels of cancer antigen 125CA 125, a protein 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 by biopsy or 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, 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 increasing, associated closely with muscle cells in the uterus, or is highly vascularizedwith lots of blood vessels infiltrating the tumor. Radiation therapy can be delivered either conventionally via the standard external X-ray or as brachytherapy, internal radiation that targets 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, 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 cancerboth initial and recurrent casestaking 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 reduces cancer risk. This includes maintaining a healthy weightobesity is a risk factor for developing endometrial cancerand exercising regularly.

For endometrial cancer, the ACS estimated in 2024 that five-year survival rates at diagnosis are approximately 95 percent for those with localized cancer. The rate was 70 percent for those with regional spread. The rate dropped to 18 percent for patients with distant spread. The cumulative survival rates for all stages of endometrial cancer was 81 percent.

In one 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 occurred within about three years after the follow-up visit.

First developed in the 2010s, immunotherapy was gaining widespread adoption by the 2020s. There are different types of immunotherapies. One type is called immune checkpoint inhibitors. These are essentially switches that activate immune system responses within a person's body. Cancer cells can block these inhibitors. Evade Pembrolizumab (Ketruda) is one type of immunotherapy drug that has been used effectively against some endometrial cancers.

Bibliography

Canavan, T. P., and N. R. Doshi. “Endometrial Cancer.” American Family Physician, vol. 59, no. 11, 1999, pp. 3069–77.

Clarke-Pearson, Daniel L, and John Soper. Gynecological Cancer Management: Identification, Diagnosis, and Treatment. Chichester, Wiley, 2010.

Fung-Kee-Fung, M., et al. “Follow-Up After Primary Therapy for Endometrial Cancer: A Systematic Review.” Gynecologic Oncology, vol. 101, no. 3, 2006, pp. 520–29. Print.

"Immunotherapy for Endometrial Cancer." American Cancer Society, 3 Aug. 2023, cancer.org/cancer/types/endometrial-cancer/about/key-statistics.html. Accessed 17 July 2024.

"Key Statistics for Endometrial Cancer." American Cancer Society, 17 Jan. 2024, www.cancer.org/cancer/types/endometrial-cancer/about/key-statistics.html. Accessed 17 July 2024.

Liu, F. S. “Molecular Carcinogenesis of Endometrial Cancer.” Taiwanese Journal of Obstetrics and Gynecology, vol. 46, no. 1, 2007, pp. 26–32.

Mundt, Arno J., Catheryn M. Yashar, and Loren K. Mell. Gynecologic Cancer. New York, Demos Medical, 2011.

Robertson G. “Screening for Endometrial Cancer.” Medical Journal of Australia, vol. 178, no. 12, 2003, pp. 657–59.

Sherman, M. E. “Theories of Endometrial Carcinogenesis: A Multidisciplinary Approach.” Modern Pathology, vol. 13, no. 3, 2000, pp. 295–308.

"Survival Rates for Endometrial Cancer." American Cancer Society, 17 Jan. 2024, cancer.org/cancer/types/endometrial-cancer/about/key-statistics.html. Accessed 17 July 2024.

Van Look, Paul, Kris Heggenhougen, and Stella R. Quah. Sexual and Reproductive Health: A Public Health Perspective. San Diego, Academic, 2011.