Medically reviewed by Dr. C.H. Weaver M.D. Medical Editor (08/2018)
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%.
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. 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. Women with a family history of uterine cancer may wish to discuss genetic testing with their physician. For more information about genetic testing, please refer to the section Genetic Testing.
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.
Hormone Replacement Therapy: Use of estrogen alone for the management of menopausal symptoms substantially increases the risk of uterine cancer. 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. 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. 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.
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.
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.
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. 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. 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 1) some risk factors can be changed (such as smoking or dietary intake), thus decreasing the risk for developing the associated cancer; and 2) 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.
Understanding DNA Damage Response or DDR and Cancer Treatment
What is DNA Damage Response or DDR?
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.
Strategies to Improve Screening and Prevention
The potential for earlier detection and higher cure rates increases with the advent of more refined screening techniques. In an effort to provide more screening options and perhaps more effective prevention strategies, researchers continue to explore new techniques for the screening and early detection of cancer.
Predictive Genetic Testing: The identification of the cancer susceptibility genes has led to predictive genetic testing for these genes. Since most uterine cancers are not the result of known inherited mutations, not all women would benefit from genetic testing. However, women who have a family history of hereditary nonpolyposis colon cancer (HNPCC) have an increased risk for carrying the HNPCC genetic abnormality. These women may benefit from undergoing a test to determine if they do carry the HNPCC genetic abnormality. An accurate genetic test can reveal a genetic mutation, but cannot guarantee that cancer will or will not develop. At this point, genetic tests are used to identify individuals who are at an increased risk of developing cancer, so that these individuals may have the option of taking preventive measures. For more information about genetic testing, please refer to the section Genetic Testing.
 American Cancer Society. Cancer Facts & Figures 2017. Available here.
 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.