Endometrial carcinoma is the most common malignancy of the female genital tract, accounting for almost one-half of all gynecologic cancers in the United States. In 2011, an estimated 46,470 new cases and 8,120 cancer-related deaths are anticipated. Endometrial carcinoma is the fourth most common cancer, ranking behind breast, lung, and colorectal cancers, and the eighth leading cause of death from malignancy in women. Overall, about 2% to 3% of women develop endometrial cancer during their lifetimes (1). Certain factors are increasing awareness of and emphasis on diagnosis and treatment of endometrial cancer. These factors include the declining incidence of cervical cancer-related deaths in the United States, prolonged life expectancy, postmenopausal use of hormone therapy, and earlier diagnosis. The availability of easily applied diagnostic tools and a clearer understanding of premalignant lesions of the endometrium led to an increase in the number of women diagnosed with endometrial cancer. Although endometrial carcinoma usually presents as early-stage disease and often is managed without radical surgery or radiotherapy, deaths from endometrial carcinoma now exceed those from cervical carcinoma in the United States. Endometrial cancer is a disease that occurs primarily in postmenopausal women and is increasingly virulent with advancing age. The definite role of estrogen in the development of most endometrial cancers is established. Any factor that increases exposure to unopposed estrogen increases the risk for endometrial cancer.
The histopathology, spread patterns, and clinicopathologic factors that affect the prognosis of endometrial cancers have become better defined. Management of endometrial cancer evolved from a program of preoperative intrauterine or external pelvic radiation followed by hysterectomy based on clinical staging, to an individualized approach using hysterectomy as primary therapy and employing additional postoperative treatment depending on surgical and pathologic findings. Further analysis and investigation are needed to determine whether this initial operative approach to treatment and staging, followed by targeted postoperative therapy, will translate into improved survival rates and lower morbidity.
There appear to be two pathogenetic types of endometrial cancer (2). Type I, accounting for about 75% to 85% of cases, occurs in younger, perimenopausal women with a history of exposure to unopposed estrogen, either endogenous or exogenous. In these women, tumors begin as hyperplastic endometrium and progress to carcinoma. These “estrogen-dependent” tumors tend to be better differentiated and have a more favorable prognosis than tumors that are not associated with hyperestrogenism. Type II endometrial carcinoma occurs in women without estrogenic stimulation of the endometrium. These spontaneously occurring cancers are not associated pathologically with endometrial hyperplasia, but may arise in a background of atrophic endometrium. They are less differentiated and associated with a poorer prognosis than estrogen-dependent tumors. These “estrogen-independent” tumors tend to occur in older, postmenopausal, thin women and are present disproportionately in AfricanAmerican and Asian women. Over the past decade, molecular genetic studies showed that these two tumor types evolve via distinct pathogenetic pathways (3) (see Type I and II Endometrial Carcinoma: Molecular Aberrations, below).
Several risk factors for the development of endometrial cancer are identified (4–9) (Table 35.1).