Overview of Uterine Cancer
Medically reviewed by Dr. C.H. Weaver M.D. Medical Editor 6/2020
The uterus is the female reproductive organ where the unborn baby grows and develops until birth. This muscular organ is connected to the vagina by the cervix and contains entrances for the two fallopian tubes, which transfer eggs from the ovaries. The uterus is a highly hormone sensitive organ with monthly bleeding and shedding cycles (menstruation) in the absence of pregnancy.
Uterine (endometrial) cancer is one of the most common gynecologic cancers in women, with more than 67,000 individuals diagnosed each year in the United States and more than 10,00 deaths from the disease annually. Fortunately approximately 80% of women diagnosed with endometrial cancer after developing abnormal uterine bleeding will have cancer limited to the uterus (stage I and II) and the majority are cured. The incidence of uterine cancer would be even higher if it weren’t for the relatively large number of hysterectomies performed for non-cancerous reasons. Surgery is the primary treatment for uterine cancer and approximately 82% of women survive 5 years after diagnosis. (1)
The growth of the most common uterine cancer, adenocarcinoma, is sensitive to female hormones. Uterine cancer usually arises from the lining of the uterus or endometrium. For most women, uterine cancer is brought to medical attention because of unanticipated or problematic bleeding from the uterus, usually occurring after menopause.
Symptoms & Signs of Uterine Cancer
Irregular vaginal bleeding is the most common presenting sign of endometrial cancer. It generally occurs early in the disease process, and is the reason why most patients are diagnosed with highly curable early stage cancer.
- Bleeding or discharge not related to menstruation
- Difficult or painful urination
- Pelvic pain
- Pain during sexual intercourse
Uterine cancer begins when healthy cells acquire a genetic change (mutation) that causes them to turn into abnormal cells. Most endometrial cancers develop sporadically, which means for no known reason.
Risk factors for Uterine Cancer
A risk factor is anything that increases a person’s chance of developing cancer. Risk factors can influence the development of cancer but most do not directly cause cancer. Many individuals with risk factors will never develop cancer and others with no known risk factors will. Some cancers however are more likely to develop in individuals with certain risk factors that increase an individual’s chance of developing cancer. The following factors may raise a person’s risk for developing endometrial cancer. (1,2)
Risk factors for endometrial cancer include the following:
- Endometrial hyperplasia (15)
- Hormone therapy (3,4)
- Tamoxifen therapy (5,6)
- Polycystic Ovarian Syndrome
- Never having children
- Early menarche and late menopause
- Family history/genetic predisposition (7,8)
- Hyperinsulinemia (9)
- Lynch Syndome
Prolonged, unopposed estrogen exposure has been associated with an increased risk of endometrial cancer. However, combined estrogen and progesterone therapy prevents the increase in risk of endometrial cancer associated with unopposed estrogen use. (3-6)
Tamoxifen, which is used for both the treatment and prevention of breast cancer is associated with an increased risk of endometrial cancer related to the estrogenic effect of tamoxifen on the endometrium. (5,6) It is important that patients who are receiving tamoxifen and experiencing abnormal uterine bleeding have follow-up examinations and biopsy of the endometrial lining.
Endometrial hyperplasia is a condition in which the endometrium (the lining of the uterus) becomes abnormally thick. Although endometrial hyperplasia is not cancer, it can lead to uterine cancer in some women. Endometrial hyperplasia is usually caused by an excess of estrogen without progesterone (female hormones). The progesterone is not made and the lining of the uterus is not shed if ovulation does not occur. This means that the endometrium may continue to grow in response to the production of estrogen.
Atypical endometrial hyperplasia is a pre-cancerous condition of the endometrium. It occurs when there is an overgrowth of abnormal cells, or it may develop from endometrial hyperplasia. In some cases, polyps (tumors) in the uterus can lead to atypical endometrial hyperplasia.
Atypical endometrial hyperplasia usually develops in older women (after menopause). But it can develop in younger women if they do not ovulate or are obese. Abnormal vaginal bleeding is the most common symptom of atypical endometrial hyperplasia. Less common symptoms include abnormal vaginal discharges or an abnormal Pap test result.
Atypical endometrial hyperplasia develops when there is no balance between the female hormones, estrogen and progesterone. This imbalance is called unopposed estrogen and it may be caused by a number of factors including:
- Hormone changes during menopause (cessation of menstrual period)
- Estrogen-hormone replacement therapy
- Breast cancer treatment, using drugs such as tamoxifen (Nolvadex®, Tamofen®)
Treatment for atypical endometrial hyperplasia depends on how different the abnormal cells are from the normal cells in the endometrium, the amount of vaginal bleeding and whether an individual you may want to have children in the future. Treatment may consist of removal of the uterus (hysterectomy) in women who are post-menopausal or progesterone therapy if childbearing is to be preserved. (15)
Diagnosis & Tests for Uterine Cancer
Doctors use many tests to find, or diagnose, cancer. They also do tests to learn if cancer has spread to another part of the body from where it started. In order to confirm the diagnosis of uterine cancer, a sample of tissue will need to be taken from the uterus and examined under a microscope. This sample may be obtained through a biopsy or through a procedure known as dilation and curettage (D&C).
Although a Pap smear may initially raise the suspicion of cancer it is not a reliable procedure for the detection of endometrial cancer.(1,2)
Endometrial biopsy: An endometrial biopsy refers to the removal of a tissue sample from the lining of the uterus (the endometrium). Endometrial biopsy may be performed in some women whose Pap test indicates atypical glandular cells.
Infrequently, it may still remain unclear whether the abnormal cells are confined to the cervix or arise from inside the uterus. In this situation, a dilatation and curettage (D and C) may be recommended. During a D and C, the cervical opening is stretched (dilated) and a curette is inserted to remove cells from the lining of the uterus and cervical canal.
There are several types of uterine cancer, which vary based on their appearance under the microscope. The most common type of uterine cancer is adenocarcinoma. Other variants of uterine cancer that behave more aggressively include serous carcinoma, uterine clear cell carcinoma and mixed type. These cancers, stage for stage, have a worse outcome than adenocarcinoma. The stage or extent of spread of cancer is the most useful predictor of survival and is relevant for treatment planning. Currently, surgery to remove the uterus, ovaries and lymph nodes is often relied upon to determine the stage of the cancer. (2)
In addition to a through history and physical exam including a pelvic examination the following procedures may be used to detect, evaluate, and determine the stage of endometrial cancer:
Transvaginal ultrasound: A procedure used to examine the vagina, uterus, fallopian tubes, ovaries, and bladder. An instrument is inserted into the vagina that causes sound waves to bounce off organs inside the pelvis. These sound waves create echoes that are sent to a computer, which creates a picture called a sonogram.
Hysteroscopy: A procedure to look inside the uterus for abnormal areas. A hysteroscope is a thin, tube-like instrument with a light and a lens for viewing. It is inserted through the vagina and cervix into the uterus to view the uterine lining and remove tissue samples, which can be checked for signs of cancer.
Imaging tests: Tests such as X-rays, CT scans, magnetic resonance imaging (MRI) and positron emission tomography (PET) are used to help determine the stage and whether the cancer has spread.
- Computed Tomography (CT) Scan: A CT scan is a technique for imaging body tissues and organs, during which X-ray transmissions are converted to detailed images, using a computer to synthesize X-ray data. A CT scan is conducted with a large machine positioned outside the body that can rotate to capture detailed images of the organs and tissues inside the body.
- Magnetic Resonance Imaging (MRI): MRI uses a magnetic field rather than X-rays, and can often distinguish more accurately between healthy and diseased tissue than a CT. An MRI gives a better picture of cancer located near bone than does CT, does not use radiation, and provides pictures from various angles that enable doctors to construct a three-dimensional image of the cancer.
- Positron emission tomography (PET): Positron emission tomography scanning is an advanced technique for imaging body tissues and organs. One characteristic of living tissue is the metabolism of sugar. Prior to a PET scan, a substance containing a type of sugar attached to a radioactive isotope (a molecule that emits radiation) is injected into the patient’s vein. The cancer cells “take up” the sugar and attached isotope, which emits positively charged, low energy radiation (positrons) that create the production of gamma rays that can be detected by the PET machine to produce a picture. If no gamma rays are detected in the scanned area, it is unlikely that the mass in question contains living cancer cells.
Stages of Uterine Cancer
In order to learn more about the most recent information available concerning the treatment of uterine cancer, click on the appropriate stage.
Stage I: Cancer does not spread outside the body of the uterus.
Stage II: Cancer involves the body of the uterus and the cervix.
Stage III: Cancer extends outside the uterus, but is confined to the pelvis.
Stage IV: Cancer involves the bladder or bowel or distant sites.
Recurrent: Cancer has returned after initial treatment.
Genomic or Biomarker Testing-Precision Cancer Medicine
The purpose of precision cancer medicine is to define the genomic alterations in the cancers DNA that are driving that specific cancer. Precision cancer medicine utilizes molecular diagnostic and genomic testing, including DNA sequencing, to identify cancer-driving abnormalities in a cancer’s genome. Once a genetic abnormality is identified, a specific targeted therapy can be designed to attack a specific mutation or other cancer-related change in the DNA programming of the cancer cells. Precision cancer medicine uses targeted drugs and immunotherapies engineered to directly attack the cancer cells with specific abnormalities, leaving normal cells largely unharmed.
Screening/Prevention of Uterine Cancer
Information about the prevention of cancer and the science of screening appropriate individuals at high-risk of developing cancer is gaining interest. Physicians and individuals alike recognize that the best “treatment” of cancer is preventing its occurrence in the first place or detecting it early when it may be most treatable.
Uterine (endometrial) cancer is the most common invasive gynecologic cancer in women, with 42,000 new cases each year. This incidence would be higher if it weren’t for the relatively large number of hysterectomies performed for non-cancerous reasons. It is estimated that approximately 7,700 women will die of uterine cancer in the United States each year. The lifetime risk of developing uterine cancer for an American woman is 2.5%. (1)
Studies show that the most common type of uterine cancer, endometroid adenocarcinoma, develops from the overgrowth of cells lining the uterus in the setting of excessive or prolonged exposure to the female hormone estrogen. Other less common uterine cancers, such as serous carcinoma, do not seem to be related to estrogen levels in the body.
The chance of an individual developing cancer depends on both genetic and non-genetic factors. A genetic factor is an inherited, unchangeable trait, while a non-genetic factor is a variable in a person’s environment, which can often be changed. Non-genetic factors may include diet, exercise, or exposure to other substances present in our surroundings. These non-genetic factors are often referred to as environmental factors. Some non-genetic factors play a role in facilitating the process of healthy cells turning cancerous (i.e. the correlation between smoking and lung cancer) while other cancers have no known environmental correlation but are known to have a genetic predisposition, meaning a person may be at higher risk for a certain cancer if a family member has that type of cancer.
Heredity or Genetic Factors
Women with a family history of uterine cancer are roughly twice as likely to develop uterine cancer as women without a family history. (2) Women who have a family history of hereditary nonpolyposis colon cancer (HNPCC; also known as Lynch Syndrome) have an increased risk for carrying the HNPCC genetic abnormality. Studies suggest that women who carry this genetic abnormality have a 40-60% lifetime risk of uterine cancer. (3)Women with a family history of uterine cancer may wish to discuss genetic testing with their physician.
Environmental or Non-Genetic Factors
Factors associated with an increased risk of developing uterine cancer include obesity and prolonged exposure to the female hormone, estrogen. Women who begin to menstruate early in life, experience a late menopause and/or have no children have the longest exposure to estrogen, and are thus, at increased risk. (2,3,4)
Hormone Replacement Therapy: Use of estrogen alone for the management of menopausal symptoms substantially increases the risk of uterine cancer.(4) As a result, women with a uterus are generally given a combination of estrogen and progestin if they choose to use postmenopausal hormones. Combined estrogen plus progestin does not appear to increase the risk of uterine cancer, but it does have a range of other health effects, including an increase in risk of breast cancer. (5)Women who are considering using hormones to manage menopausal symptoms are advised to discuss the risks and benefits with their physician.
Oral Contraceptives: Use of most types of oral contraceptives appears to reduce the risk of uterine cancer as well as ovarian cancer. (6) Women may wish to talk with their doctor about which oral contraceptive is right for them.
Tamoxifen: Tamoxifen is a hormonal therapy drug used for the prevention and treatment of breast cancer. Although tamoxifen reduces the risk of breast cancer, it increases the risk of uterine cancer. However, since the majority of uterine cancers will be detected at an early stage when they are highly curable, the overall benefit of tamoxifen treatment in breast cancer patients is believed to outweigh the risk of uterine cancer. All women who have a uterus and are receiving tamoxifen therapy should undergo regular gynecologic examinations. (6,7)
Obesity: Obesity substantially increases the risk of uterine cancer. Studies have reported that obese women are between three and five times more likely to develop endometrial cancer than women with a body mass index (BMI) less than 23. Some researchers have estimated that roughly 40 percent of all endometrial cancers may be related to obesity. (8-10)
Prevention of Uterine Cancer
Although questions remain about the causes and prevention of uterine cancer, research suggests that certain behaviors are likely to reduce risk.
Maintain or achieve a healthy body weight: Effective approaches to weight management generally include a combination of physical activity and a healthy diet. Eating a healthy diet involves watching the total number of calories you consume, as well as making calories count by eating foods rich in important nutrients. To reduce the number of calories in your diet – while getting the nutrients you need—try eating smaller portion sizes, and reducing the amount of added sugars, saturated and trans fats, and alcohol in your diet. Replace these foods with fruits, vegetables, and whole grains.
For certain subsets of patients, prescription weight loss medications or surgery may be appropriate if other approaches to weight loss have failed. (11)
Engage in regular physical activity: in addition to contributing to weight management, regular physical activity appears to reduce the risk of several types of cancer, including uterine cancer. (12) Exercise guidelines for adults recommend at least 2 ½ hours of moderate-intensity aerobic activity every week (or 1 ¼ hours of vigorous-intensity aerobic activity) along with muscle strengthening activities on two or more days per week. (13) Moderate-intensity activity includes brisk walking and cycling on level terrain. Vigorous activity includes cycling or walking up hills and jogging. Talk with your doctor before beginning an exercise program.
Screening and Early Detection of Uterine Cancer
For many types of cancer, progress in the areas of cancer screening and treatment has offered promise for earlier detection and higher cure rates. The term screening refers to the regular use of certain examinations or tests in persons who do not have any symptoms of a cancer but are at high-risk for that cancer. When individuals are at high-risk for a type of cancer, this means that they have certain characteristics or exposures, called risk factors that make them more likely to develop that type of cancer than those who do not have these risk factors. The risk factors are different for different types of cancer. An awareness of these risk factors is important because
- Some risk factors can be changed (such as smoking or dietary intake), thus decreasing the risk for developing the associated cancer; and
- Persons who are at high-risk for developing a cancer can often undergo regular screening measures that are recommended for that cancer type. Researchers continue to study which characteristics or exposures are associated with an increased risk for various cancers, allowing for the use of more effective prevention, early detection, and treatment strategies.
Starting at menopause, women at average or increased risk of uterine cancer should be informed of the symptoms of uterine cancer, and should report any unexpected bleeding or spotting to their physicians.(14)
Women at very high risk of uterine cancer as a result of a known or suspected HNPCC gene mutation may wish to begin annual testing for endometrial cancer starting at the age of 35 after thoroughly discussing the potential risks and benefits with their physician.
- American Cancer Society: Cancer Facts and Figures 2017. Atlanta, Ga: American Cancer Society, 2017.
- Ward KK, Shah NR, Saenz CC, et al.: Cardiovascular disease is the leading cause of death among endometrial cancer patients. Gynecol Oncol 126 (2): 176-9, 2012.
- Ziel HK, Finkle WD: Increased risk of endometrial carcinoma among users of conjugated estrogens. N Engl J Med 293 (23): 1167-70, 1975.
- Jick SS, Walker AM, Jick H: Estrogens, progesterone, and endometrial cancer. Epidemiology 4 (1): 20-4, 1993.
- van Leeuwen FE, Benraadt J, Coebergh JW, et al.: Risk of endometrial cancer after tamoxifen treatment of breast cancer. Lancet 343 (8895): 448-52, 1994.
- Fisher B, Costantino JP, Redmond CK, et al.: Endometrial cancer in tamoxifen-treated breast cancer patients: findings from the National Surgical Adjuvant Breast and Bowel Project (NSABP) B-14. J Natl Cancer Inst 86 (7): 527-37, 1994.
- Lynch HT, Lynch J, Conway T, et al.: Familial aggregation of carcinoma of the endometrium. Am J Obstet Gynecol 171 (1): 24-7, 1994.
- Lu KH, Schorge JO, Rodabaugh KJ, et al.: Prospective determination of prevalence of lynch syndrome in young women with endometrial cancer. J Clin Oncol 25 (33): 5158-64, 2007
- Nead KT, Sharp SJ, Thompson DJ, et al.: Evidence of a Causal Association Between Insulinemia and Endometrial Cancer: A Mendelian Randomization Analysis. J Natl Cancer Inst 107 (9): , 2015.
- Frederick PJ, Straughn JM. The role of comprehensive surgical staging in patients with endometrial cancer. Cancer Control. 2009;16:23-29.
Screening & Prevention:
- American Cancer Society: Cancer Facts and Figures 2017. Atlanta, Ga: American Cancer Society, 2017.
- Lucenteforte E, Talamini R, Montella M et al. Family history of cancer and the risk of endometrial cancer. European Journal of Cancer Prevention. 2009;18:95-9.
- Meyer LA, Broaddus RR, Lu KH. Endometrial cancer and Lynch Syndrome: Clinical and pathologic considerations. Cancer Control. 2009;16:14-22.
- Furness S, Roberts H, Marjoribanks J, Letaby A, Hickey M, Farquhar C. Hormone therapy in postmenopausal women and risk of endometrial hyperplasia. Cochrane Database of Systematic Reviews. 2009;2:CD000402.
- Chlebowski RT, Kuller LH, Prentice RL et al. Breast cancer after use of estrogen plus progestin in postmenopausal women. New England Journal of Medicine. 2009; 360(6):573-87.
- Hannaford PC, Selvaraj S, Elliott AM et al. Cancer risk among users of oral contraceptives: cohort data from the Royal College of General Practitioner’s oral contraception study. British Medical Journal. 2007;335:651.
- Fisher B, Costantino JP, Wickerham DL et al. Tamoxifen for the Prevention of Breast Cancer: Current Status of the National Surgical Adjuvant Breast and Bowel Project P-1 Study. Journal of the National Cancer Institute. 2005;97:1652-62.
- Trentham-Dietz A, Nichols HB, Hamptom JM, Newcomb PA. Weight Change and Risk of Endometrial Cancer. International Journal of Epidemiology. 2006;35:151-158.
- Schouten LJ, Goldbohm RA, van den Brandt PA. Anthropometry, Physical Activity, and Endometrial Cancer Risk: Results from The Netherlands Cohort Study. Journal of the National Cancer Institute. 2004;96:1635-8.
- Kaaks R, Lukanova A, Kurzer MS. Obesity, Endogenous Hormones, and Endometrial Cancer Risk: A Synthetic Review. Cancer Epidemiology, Biomarkers, and Prevention. 2002;11:1531-1543
- Manson JE, Skerrett PJ, Greenland P, VanItallie TB. The Escalating Pandemics of Obesity and Sedentary Lifestyle: A Call to Action for Clinicians. Archives of Internal Medicine. 2004;164:249-258.
- Voskuil DW, Monninkhof EM, Elias SG et al. Physical activity and endometrial cancer risk, a systematic review of current evidence. Cancer Epidemiol Biomarkers Prev. 2007;16:639-48.
- Physical Activity for Everyone: How much physical activity do you need? Centers for Disease Control and Prevention Web site. Available here. Accessed September 14, 2009.
- Smith RA, Cokkinides V, Brawley OW. Cancer screening in the United States, 2009: A review of current American Cancer Society guidelines and issues in cancer screening. CA Cancer J Clin 2009; 59:27-41