Overview

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 36,100 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 6,500 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%.

There has been an increase in the incidence of, but not mortality from, uterine cancer since the mid 1970s, which has been attributed to the use of hormone replacement therapy for treatment of menopausal symptoms. 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 twice as likely to develop uterine cancer than women without a family history. Women who have a family history of hereditary nonpolyposis colon cancer (HNPCC) have an increased risk for carrying the HNPCC genetic abnormality. Studies suggest that women who carry this genetic abnormality have a 10-fold increased risk of uterine cancer and a 20% incidence of uterine cancer by the age of 70. 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, a high-fat diet and a 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 the highest risk. Completion of at least one pregnancy appears to lower the risk of uterine cancer by 50%, as after the birth of the first child, the risk of developing uterine cancer appears to decrease with increasing age. The risk also decreases in proportion to the number of induced abortions. Women who take oral contraceptives also appear to have a reduction in the incidence of uterine cancer.

Hormone Replacement and Uterine Cancer: Women who take estrogen replacement therapy to control menopausal symptoms have a 4 to 8-fold increase in the risk of developing uterine cancer. This risk increases with the duration of use. For example, after 5 or more years of estrogen use, the risk of developing uterine cancer increases to 10 to 30-fold. The risk appears to last for 10 years or more after discontinuation of estrogen replacement therapy. When this information was made public, there was a decline in the use of estrogen replacement and a decline in the incidence of uterine cancer. However, women need to consider all risks and benefits before discontinuing hormone replacement for treatment of menopause because the benefits of hormone replacement therapy may outweigh the risk of cancer.

There is some evidence that adding progesterone to estrogen for the treatment of menopausal symptoms can decrease the risk of uterine cancer that is presented by estrogen; however, there is also evidence that this strategy increases the risk of breast cancer. The main issue for women taking hormone replacement is to have periodic gynecologic evaluations to detect early uterine cancer. With this strategy, women can both achieve the benefits of hormone therapy and detect uterine cancer early when it is small and curable.

Tamoxifen and Uterine Cancer: Tamoxifen is a chemopreventive drug that blocks estrogen from entering the cells. Tamoxifen and other anti-estrogens are commonly used in the treatment of breast cancer, but have also proven successful in the prevention of breast cancer in women at high-risk.

One uncommon complication of tamoxifen therapy is uterine cancer. Several clinical studies around the world have evaluated the risks and benefits of tamoxifen. The results of the National Cancer Institute clinical study evaluating tamoxifen were presented in 1998. During this study, 13,388 women at high risk of developing breast cancer were treated with either tamoxifen or placebo for 5 years. While the results indicated a 45% reduction in the development of breast cancer, they also showed an increase in the risk of uterine cancer, as 33 women treated with tamoxifen developed uterine cancer, compared with only 14 women in the placebo group. All of the uterine cancers occurring in the tamoxifen group were early stage I cancers.

Since the majority of uterine cancers will be detected at an early stage when they are highly curable, the overall benefit of anti-estrogen treatment in breast cancer patients probably outweighs the risk of uterine cancer. All women who have a uterus and are receiving anti-estrogen therapy should undergo regular gynecologic examinations.

Furthermore, in response to the risks posed by tamoxifen, newer anti-estrogens have emerged. Selective estrogen receptor modulators (SERM) are believed to have positive effects on bones as well as anti-estrogen effects on breast cancer without increasing the risk of uterine cancer. For more information, please refer to the section Hormonal Therapy.

Prevention of Uterine Cancer

Cancer is largely a preventable illness. Two-thirds of cancer deaths in the U.S. can be linked to tobacco use, poor diet, obesity, and lack of exercise. All of these factors can be modified. Nevertheless, an awareness of the opportunity to prevent cancer through changes in lifestyle is still under-appreciated.

Decreasing body weight and reducing exposure to estrogen may decrease the risk of developing uterine cancer. The addition of progesterone to estrogen may also decrease the risk of developing uterine cancer in women taking hormone replacement for menopausal symptoms. There is evidence to suggest that the use of combined hormone therapy in the form of oral contraceptives can also reduce the risk of uterine cancer by up to 40% if used for at least a year.

Diet: Diet is a fertile area for immediate individual and societal intervention to decrease the risk of developing certain cancers. Numerous studies have provided a wealth of often-contradictory information about the detrimental and protective factors of different foods.

There is convincing evidence that excess body fat substantially increases the risk for many types of cancer. While much of the cancer-related nutrition information cautions against a high-fat diet, the real culprit may be an excess of calories. Studies indicate that there is little, if any, relationship between body fat and fat composition of the diet. These studies show that excessive caloric intake from both fats and carbohydrates lead to the same result of excess body fat. The ideal way to avoid excess body fat is to limit caloric intake and/or balance caloric intake with ample exercise.

It is still important, however, to limit fat intake, as evidence still supports a relationship between cancer and polyunsaturated, saturated and animal fats. Specifically, studies show that high consumption of red meat and dairy products can increase the risk of certain cancers. One strategy for positive dietary change is to replace red meat with chicken, fish, nuts and legumes.

High fruit and vegetable consumption has been associated with a reduced risk for developing at least 10 different cancers. This may be a result of potentially protective factors such as carotenoids, folic acid, vitamin C, flavonoids, phytoestrogens and isothiocyanates. These are often referred to as antioxidants.

There is strong evidence that moderate to high alcohol consumption also increases the risk of certain cancers. One reason for this relationship may be that alcohol interferes with the availability of folic acid. Alcohol in combination with tobacco creates an even greater risk of certain types of cancer.

Exercise: Higher levels of physical activity may reduce the incidence of some cancers. According to researchers at Harvard, if the entire population increased their level of physical activity by 30 minutes of brisk walking per day (or the equivalent energy expenditure in other activities), we would observe a 15% reduction in the incidence of colon cancer. The association between exercise and uterine cancer is not as well defined.

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.

Periodic gynecologic evaluation is crucial for the early detection of uterine cancer. All women should undergo regular physical examinations and patients on hormone replacement therapy or tamoxifen might consider monitoring with transvaginal sonography (ultrasound examination) and hysteroscopy (endoscopic evaluation of the uterus). The ability to detect abnormalities in the uterus may be improved with a test called sonohysterograpy, where a salt-water solution is infused into the uterus before the transvaginal sonography is performed. This is a safe and inexpensive improvement over conventional ultrasound examinations.

For women taking tamoxifen, annual examinations beginning 2-3 years after the start of treatment are currently advised. Abnormal bleeding or undiagnosed postmenopausal bleeding warrants immediate evaluation with endometrial biopsy. Ultrasound performed through the vagina for the evaluation of bleeding can also be used in some patients instead of immediate biopsy.

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.

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