Epidemiology of Endometrial Cancer

Incidence and mortality

Endometrial cancer is the most common invasive gynecologic cancer in U.S. women, with an estimated 42,160 new cases expected to occur in 2009 and an estimated 7,780 women expected to die of the disease.[1] Endometrial cancer is primarily a disease of postmenopausal women with a mean age at diagnosis of 60 years.[2] Age-adjusted endometrial cancer incidence in the United States has declined since 1975, with a transient increase in incidence occurring from 1973 to 1978, which was associated with estrogen therapy, also known as hormone therapy;[3] there was no associated increase in mortality. The endometrial cancer mortality rate has declined steadily from 1974 to the present. Most cases of endometrial cancer are diagnosed because of symptoms, which are nonetheless "early" stage and have high survival rates.

Risk Factors

Estrogen therapy unopposed by progesterone therapy is a cause of endometrial cancer in women with an intact uterus. However, women taking combination estrogen-progesterone therapy (hormone therapy) exhibit similar risk to women who do not take postmenopausal hormone therapy.[4,5,6] [7,8] Tamoxifen therapy is also a cause of endometrial cancer. Results from the National Surgical Adjuvant Breast and Bowel Project P-1 trial, report a doubling of the risk of endometrial cancer associated with an annual rate of 2.30 per 1,000 for women taking tamoxifen compared with 0.91 per 1,000 for women receiving placebo; the increased risk was seen primarily in postmenopausal women.[9]

In addition to the increased risk of developing endometrial cancer that is observed in women who use unopposed estrogen therapy or tamoxifen, a number of additional risk factors have been identified, and most appear to be related to estrogenic effects. Among these factors are obesity, a high-fat diet, and reproductive factors such as nulliparity, polycystic ovarian syndrome, early menarche, and late menopause. Hereditary nonpolyposis colorectal cancer (HNPCC) syndrome is associated with a markedly increased risk of endometrial cancer compared with women in the general population. Among women who are HNPCC carriers, the estimated cumulative incidence of endometrial cancer ranges from 20% to 60% by age 70 years (refer to the PDQ summary on Genetics of Colorectal Cancer for more information).[10,11,12] This risk appears to differ slightly based on the germline mutation; for MLH1 carriers the lifetime risk at age 70 years is 25% while MSH2 mutation carriers have a 35% to 40% lifetime risk of endometrial cancer by age 70 years. The mean age of diagnosis for MLH1 or MSH2 carriers is 47 years compared with 60 years for noninherited forms of endometrial cancer.[13] The prognosis and survival are similar between HNPCC-related and noninherited forms of endometrial cancer.[14]