Cancer of the endometrium is the most common gynecologic cancer in the United States, with more than 60,000 new cases diagnosed annually.
Endometrial cancers can be divided into 2 subtypes based on pathophysiology:
Type 1 includes endometrioid and mucinous carcinoma and comprise about 80% of all endometrial cancers. They are associated with chronic exposure to elevated estrogen levels.
Type 2 endometrial cancers are those that are more likely to grow outside of the uterus and include serous carcinoma, clear-cell carcinoma, undifferentiated carcinoma, and carcinosarcoma. They are not associated with exposure to high levels of unopposed estrogens.
Type 1 endometrial cancers are the subject of this chapter.
Abnormal uterine bleeding is the most common symptom, but a woman may also experience vaginal discharge, weight loss, abdominal or pelvic pain, dysuria, or dyspareunia. Uterine bleeding in any postmenopausal woman should be further evaluated.
Most endometrial cancers are slow-growing and are discovered at an early stage. Stage 1 endometrial cancer, localized to the uterus only, has a 5-year survival rate of > 90%. Five-year survival for Stage III, cancer that has spread throughout the pelvis, is about 45%.
The main risk for developing endometrial cancer comes from prolonged exposure to excess endogenous or exogenous estrogen in the absence of opposition by progestin. Common sources of endogenous estrogen include:
- Obesity. Obesity is frequently associated with endometrial cancer, presumably due to the peripheral conversion of androgens to estrogen in adipose tissue, which leads to greater endogenous estrogen concentrations in persons with obesity., Compared with normal-weight women, women with body mass index ≥ 30 have a much greater risk of being diagnosed with endometrial cancer, which rises progressively with higher body weight. A woman with body mass index ≥ 40 is 7 times more likely to develop endometrial cancer compared with a normal-weight woman. The rising incidence of obesity in recent decades has increased endometrial cancer diagnoses in women aged < 50 years by 2% each year from 1992-2012.
- Polycystic ovary syndrome. Anovulation from polycystic ovary syndrome or other causes results in persistent exposure to unopposed endogenous estrogen.
- Prolonged exposure to estrogen. Early menarche, late menopause, and nulliparity (especially when due to anovulation) may increase the risk for endometrial cancer.
- Estrogen-secreting tumors. Although rare, tumors that secrete estrogen increase the risk of endometrial carcinoma.
Exogenous estrogen sources include:
- Menopausal estrogen therapy. Estrogen therapy without progestin significantly increases the risk of endometrial cancer.
- In postmenopausal women using tamoxifen as therapy for breast cancer, risk of endometrial cancer is 2 to 3 times that of the general population.,
Other risk factors include:
Age. Risk increases with age. The disease primarily affects women over age 50.
Race. Endometrial cancer is more common in Black women than in White women, and Black women often have worse outcomes from the disease.
Diabetes and hypertension. Women with hypertension and diabetes (particularly type 2) have an increased risk for endometrial cancer, which may reflect the presence of common risk factors such as obesity.,
Genetics. Women who have a 1st-degree relative with endometrial cancer are at increased risk of developing endometrial cancer. A family history of hereditary nonpolyposis colorectal cancer (Lynch syndrome) greatly increases the risk as well.
Exercise. Regular physical activity is associated with a 20-30% reduction in risk.
The patient’s medical history may reveal abnormal vaginal bleeding or discharge in addition to nonspecific findings, such as lower abdominal pain, dysuria, and dyspareunia. Pelvic exam may reveal uterine enlargement but cannot distinguish whether it is benign or malignant. An incidental Pap smear finding of either normal or atypical endometrial cells increases the chance of a uterine cancer diagnosis. However, a normal Pap result does not rule out endometrial cancer.
Endometrial biopsy is indicated in any postmenopausal woman with vaginal bleeding and should follow any Pap smear that shows endometrial cells, whether normal or atypical, because the mere presence of endometrial cells may be a sign of endometrial pathology. Biopsy may not be necessary in asymptomatic premenopausal women.
Hysteroscopy or dilation and curettage can also provide endometrial tissue samples, but these procedures are far more invasive, require anesthesia, and have more frequent complications compared with endometrial biopsy. Although it is the preferred procedure for diagnosis, hysteroscopy can be reserved for cases in which endometrial biopsy is inconclusive, but the pretest probability for cancer is high.
Transvaginal ultrasound can measure the endometrial thickness, which should be less than 4 mm in a postmenopausal woman. Annual endometrial biopsy may be used to screen women with a personal or family history of hereditary nonpolyposis colorectal cancer gene mutations (Lynch syndrome).
Endometrial cancer staging requires hysterectomy and bilateral salpingo-oophorectomy. Perioperative inspection of the opened uterus, along with clinical history, helps determine whether lymphadenectomy is required. Selective lymphadenectomy reduces associated morbidity and mortality. Peritoneal fluid cytology should be obtained during surgery for purposes of staging. Stages are defined by the International Federation of Gynecology and Obstetrics and are based on localization or degree of spread of the cancer. The International Federation of Gynecology and Obstetrics provides a grading scale based on the degree of glandular differentiation.
Surgical cytoreduction, radiation, hormone therapy, and chemotherapy may all be part of a treatment regimen. Progestin therapy without hysterectomy may be used in women with the lowest stage or grade of disease who would like to preserve their fertility.
As with many cancers, the risk for uterine cancers appears to be associated with greater intakes of foods found in Western diets (animal products, refined carbohydrates)., Risk may be lower among women whose diets are high in fruits, vegetables, whole grains, and legumes. The lower risk in persons eating plant-based diets may be related to a reduced amount of free hormones circulating in the blood and/or to a protective effect of micronutrients found in these diets.
The following factors are under study for possible protective effects:
Avoiding meat, dairy products, and saturated fat. The associations between meat and endometrial cancer have not been consistent; overall, case-control studies have identified increased risk of endometrial cancer associated with red meat in particular, a finding not reflected in most prospective studies., However, connections have emerged between components of meat (heme iron and saturated fat) and this cancer. The Swedish Mammography Cohort found significant relationships between both heme iron (found in both red and white meat) and liver consumption and endometrial cancer. A dose-response analysis of fat intake and endometrial cancer concluded that increasing total fat intake by 10% of calories increased risk for this cancer by 5%. However, increasing saturated fat intake by 10 g/1000 kcals was associated with a much greater risk (17%). This implies that the effect of saturated fats on increasing risk for endometrial cancer is more than 3 times that of other types of fat.
Dairy products may contribute to these effects, as shown in the Nurses’ Health study, which found a 40% greater risk for endometrial cancer in postmenopausal nonusers of hormone replacement therapy who consumed 3 or more dairy servings per day, compared with those consuming less than 1. Some evidence indicates that this association is due to the influence of dietary fat on adiposity and, consequently, on circulating estrogens.
Fruits, vegetables, and legumes. Although the NIH-AARP study found no significant relationship between fruit and vegetable intakes and endometrial cancer, previous studies suggested that these foods may be associated with reductions in risk by as much as 50-60%.,, In the American Cancer Society’s Cancer Prevention Study II Nutrition Cohort of more than 41,000 women, protective effects of vegetables and fruits (20% and 25% lower risk, respectively) for those consuming the highest amounts of these foods were identified only in women who had never used hormone therapy.
A 2015 meta-analysis showed that a high soy intake is associated with a nearly 20% lower endometrial cancer risk. The reason may be that soy stops the conversion of other steroids like testosterone into estrogen, behaving as an aromatase inhibitor.
Avoidance of sugar and high-glycemic-index carbohydrates. The Iowa Women’s Health Study found a 78% greater risk for endometrial cancer in women who consumed the most sugar-sweetened beverages, compared with those who consumed the lowest amount. A meta-analysis comparing women whose diets had the highest compared with the lowest glycemic load found a roughly 20% higher risk for those in the former category.
Coffee and green tea drinking. Women who consume the most coffee were found to have a 20% lower risk for endometrial cancer when compared with those who consumed the lowest amount, and high coffee consumers who had never been treated with hormone replacement therapy were found to have a 40% lower risk. Similarly, green tea drinkers had a nearly 20% lower risk for endometrial cancer in the highest compared with lowest intake group. These effects may be due to the ability of caffeine and other methylxanthines in coffee to increase sex hormone-binding globulin and increase insulin sensitivity; for green tea, actions may include promotion of apoptosis, cell cycle arrest, up-regulation of glutathione-S-transferases that inactivate carcinogens, and antiestrogen effects.,
Moderating alcohol consumption. There appears to be a J-shaped relationship between ethanol consumption and risk for endometrial cancer. Women who consume between one-half and 1 drink per day were found to have a 4-7% lower risk, while women who drank 2.5 or more than 2.5 servings per day had a 14% and 25% greater risk, respectively, compared with nondrinkers or those who drank only occasionally.
Other nutrition and lifestyle recommendations. Limiting high-energy-dense foods and high salt (or foods high in sodium), exercising regularly, and maintaining a healthy weight may reduce cancer risk. Following a plant-based diet helps achieve a healthy weight and provides a higher diet quality compared with other eating patterns. There has been extensive research demonstrating that plant-based diets reduce the risk of other cancers such as breast, colorectal, and gastrointestinal cancers.
See Basic Diet Orders chapter.
Regular physical activity.
Maintain a healthy weight.
What to Tell the Family
The 5-year survival rate for uterine cancers is high, particularly with early detection and treatment. The family may support the patient’s adherence to diet and exercise recommendations by adopting the same practices, which are likely to improve their health as well. Some evidence suggests that following a low-fat, plant-based diet, maintaining a healthy weight, and getting regular exercise may reduce the risk of this disease.
Genetic counseling should be considered for family members of patients diagnosed with endometrial cancer who have a strong family history of endometrial cancer or colon cancer (Lynch syndrome).
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