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In the United States, endometrial cancer is the most common gynecologic malignancy. Risk factors include obesity and advancing age. As these factors are now more prevalent, the incidence of endometrial cancer continues to increase. Fortunately, patients usually seek medical attention early due to vaginal bleeding, and endometrial biopsy leads quickly to diagnosis. The primary treatment is hysterectomy with bilateral salpingo-oophorectomy (BSO) and staging lymphadenectomy for most women. Three quarters will have stage I disease that is curable by surgery alone. Patients with more advanced disease typically require postoperative combination chemotherapy, radiotherapy, or both.


In the United States, women have a 3-percent lifetime risk of developing endometrial cancer. Although an estimated 54,870 new cases were diagnosed, only 10,170 deaths are expected in 2015. As noted, most patients are diagnosed early and subsequently cured. As a result, endometrial cancer is the fourth leading cause of cancer, but the seventh leading cause of cancer deaths among women (Siegel, 2015).

Endometrial adenocarcinomas are categorized as type I or type II based on histology. Type I, that is, endometrioid type, makes up 80 to 90 percent of all cases (Felix, 2010). The other 10 to 20 percent are type II cancers, namely, the non-endometrioid histologic types that include serous and clear cell adenocarcinomas. Risk factors for developing endometrial cancer are numerous (Table 33-1). Risks specifically for type I cancers are associated with an excess-estrogen environment.

TABLE 33-1Factors Affecting Endometrial Cancer Risk

Of these, obesity is the most common cause of endogenous overproduction of estrogen. Excessive adipose tissue increases peripheral aromatization of androstenedione to estrone. In premenopausal women, elevated estrone levels trigger abnormal feedback in the hypothalamic-pituitary-ovarian axis. The clinical result is oligo- or anovulation. In the absence of ovulation, the endometrium is exposed to virtually continuous estrogen stimulation without subsequent progestational effect and without menstrual withdrawal bleeding.

Unopposed estrogen therapy is the next most important potential inciting factor. Fortunately, the malignant potential of continuously administered estrogen was recognized more than three decades ago (Smith, 1975). Currently, it is rare to encounter a woman with a uterus who has taken unopposed estrogen for years. Instead, combined estrogen plus progestin hormonal replacement therapy (combination HRT) is routinely prescribed for postmenopausal women with a uterus to reduce estrogen-related endometrial cancer risk (Strom, 2006). Moreover, ...

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