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Cancer of the lining of the uterine corpus, endometrial cancer (EC), is the most common gynecologic malignancy in the United States. Adenocarcinoma of the endometrium, the most common histologic subtype, ranks fourth in cancer prevalence after breast, lung, and colorectal. Endometrial adenocarcinoma will account for approximately 7500 deaths this year and is the eighth leading cause of death from malignancy in women (1).

Endometrial cancer is primarily a disease of postmenopausal women. Ninety percent of cases are diagnosed in women over the age of 50 with a median age of diagnoses at 61. About 20 to 25% of women diagnosed are premenopausal with fewer than 5% under the age of 40 (2).

Risk Factors

Both genotypic and phenotypic risk factors are noted in the development of EC. There are two types of EC as well as a hereditary of genetic variant. Type I tumors are the most common, accounting for about 75% of endometrial cancers, and are associated with chronic exposure to exogenous or endogenous estrogen. These tumors arise on a background of benign endometrial hyperplasia and progress to carcinomas, have minimal myometrial invasion, and usually have more favorable prognoses (3). Type II disease represents approximately 10 to 20% of cases and generally consists of high-grade tumors with myometrial invasion. These neoplasms are associated with less differentiated cell type and have worse prognosis than type I. Type II disease is not associated with hormone exposure. Finally, genetic disease can represent the remainder of up to 10% of cases with Lynch II syndrome or hereditary nonpolyposis colorectal cancer (HNPCC) being the most common. Endometrial cancer is the most common cancer associated with HNPCC with 40 to 60% lifetime risk of developing the disease (4) (Table 29-1).

Table 29–1. Characteristic Features of Types I and II Uterine Cancer

Unopposed Estrogen

The association between chronic exposure to estrogen replacement therapy and EC is well-established, and both the duration and dose of estrogen affect the risk. The relative risk of developing EC for women taking estrogen replacement therapy is two to ...

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