Epidemiology of Endometrial Cancer
        Incidence and mortality
Risk Factors

Epidemiology of Endometrial Cancer

Incidence and mortality

Endometrial cancer is the most common invasive gynecologic cancer in U.S. women, with an estimated 40,100 new cases expected to occur in 2008 and an estimated 7,470 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 declined since 1975, with the greatest decline between 1978 and 1988.[3] A transient increase in incidence occurring from 1973 to 1978 was associated with estrogen replacement therapy (ERT), also known as hormone therapy (HT),[4] but there was no associated increase in mortality. The endometrial cancer mortality rate has declined steadily from 1974 to the present.

Several factors affect the interpretation of statistics for noncervical endometrial cancer from 1978 onward. From the Surveillance Epidemiology and End Results registries, uterine tumors are classified as cervical, corpus, and not otherwise specified (NOS). Corpus and NOS categories are usually combined to reflect noncervical carcinoma of the uterus. In the mid-1980s, a pathological review of cases in the NOS category found that 11% came from the uterine cervix.[5] The practice of combining corpus with NOS cases, some of which are of cervical origin, overestimates the total amount of noncervical carcinomas of the uterus. Since the 1970s, the percentage of cases in the NOS category has declined to a current level of about 2% or less of the total cases, reducing the opportunity for an overestimate. In addition, rates of endometrial cancer are not adjusted for the substantial, but variable, portion of the female population that has undergone hysterectomy. One study estimated that adjustment for age-specific hysterectomy yielded an endometrial cancer incidence rate that was approximately 20% higher.[6] These examples illustrate how observed trends in the reported incidence of and mortality from endometrial cancer have been affected by temporal factors.

ERT/HT unopposed by progesterone therapy is a cause of endometrial cancer in women with an intact uterus. However, women taking combination estrogen-progesterone replacement therapy (HRT/HT) exhibit similar risk to women who do not take postmenopausal HT.[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 an annual rate of endometrial cancer 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 ERT/HT 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, high-fat diet, 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).[10-12] 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]

Major differences exist between black and white women in stages of endometrial cancer at detection and at subsequent survival. Although the incidence of endometrial cancer is lower among black women, mortality is higher. The National Cancer Institute initiated a Black/White Cancer Survival Study [15] and concluded that higher-grade and more aggressive histologies appear to be related to excess risk of advanced-stage disease for black women. It is difficult to disentangle the effects that biology and socioeconomic status may have on the lower survival rates of African American women with endometrial cancer. Evidence suggests that lower income is associated with advanced-stage disease, lower probability of undergoing a hysterectomy, and lower survival rates.[16] Others, however, assert that there is no black/white difference in the interval from patient-reported symptoms to initial medical consultation, making it unlikely that patient delay after onset of symptoms could explain much of the excess of advanced-stage disease found in black women.[17] Further research is necessary to understand why black women tend to be diagnosed with more aggressive disease and have a higher probability of dying than white women, despite their lower incidence of endometrial cancer.

References

1. American Cancer Society.: Cancer Facts and Figures 2008. Atlanta, Ga: American Cancer Society, 2008. Also available online. Last accessed May 30, 2008. 
   
   
2. American Cancer Society.: Detailed Guide: Endometrial Cancer: What are the Risk Factors for Endometrial Cancer? Atlanta, Ga: American Cancer Society, 2005. Available online. Last accessed January 16, 2008. 
   
   
3. Ries LAG, Eisner MP, Kosary CL, et al.: SEER Cancer Statistics Review, 1975-2001. Bethesda, Md: National Cancer Institute, 2004. Also available online. Last accessed January 16, 2008. 
   
   
4. Jick H, Walker AM, Rothman KJ: The epidemic of endometrial cancer: a commentary. Am J Public Health 70 (3): 264-7, 1980.  [PUBMED Abstract]
   
   
5. Percy CL, Miller BA, Gloeckler Ries LA: Effect of changes in cancer classification and the accuracy of cancer death certificates on trends in cancer mortality. Ann N Y Acad Sci 609: 87-97; discussion 97-9, 1990.  [PUBMED Abstract]
   
   
6. Howe HL: Age-specific hysterectomy and oophorectomy prevalence rates and the risks for cancer of the reproductive system. Am J Public Health 74 (6): 560-3, 1984.  [PUBMED Abstract]
   
   
7. Pike MC, Peters RK, Cozen W, et al.: Estrogen-progestin replacement therapy and endometrial cancer. J Natl Cancer Inst 89 (15): 1110-6, 1997.  [PUBMED Abstract]
   
   
8. Persson I, Weiderpass E, Bergkvist L, et al.: Risks of breast and endometrial cancer after estrogen and estrogen-progestin replacement. Cancer Causes Control 10 (4): 253-60, 1999.  [PUBMED Abstract]
   
   
9. Fisher B, Costantino JP, Wickerham DL, et al.: Tamoxifen for prevention of breast cancer: report of the National Surgical Adjuvant Breast and Bowel Project P-1 Study. J Natl Cancer Inst 90 (18): 1371-88, 1998.  [PUBMED Abstract]
   
   
10. Watson P, Vasen HF, Mecklin JP, et al.: The risk of endometrial cancer in hereditary nonpolyposis colorectal cancer. Am J Med 96 (6): 516-20, 1994.  [PUBMED Abstract]
    
    
11. Aarnio M, Mecklin JP, Aaltonen LA, et al.: Life-time risk of different cancers in hereditary non-polyposis colorectal cancer (HNPCC) syndrome. Int J Cancer 64 (6): 430-3, 1995.  [PUBMED Abstract]
    
    
12. Aarnio M, Sankila R, Pukkala E, et al.: Cancer risk in mutation carriers of DNA-mismatch-repair genes. Int J Cancer 81 (2): 214-8, 1999.  [PUBMED Abstract]
    
    
13. Berends MJ, Wu Y, Sijmons RH, et al.: Toward new strategies to select young endometrial cancer patients for mismatch repair gene mutation analysis. J Clin Oncol 21 (23): 4364-70, 2003.  [PUBMED Abstract]
    
    
14. Boks DE, Trujillo AP, Voogd AC, et al.: Survival analysis of endometrial carcinoma associated with hereditary nonpolyposis colorectal cancer. Int J Cancer 102 (2): 198-200, 2002.  [PUBMED Abstract]
    
    
15. Barrett RJ 2nd, Harlan LC, Wesley MN, et al.: Endometrial cancer: stage at diagnosis and associated factors in black and white patients. Am J Obstet Gynecol 173 (2): 414-22; discussion 422-3, 1995.  [PUBMED Abstract]
    
    
16. Madison T, Schottenfeld D, James SA, et al.: Endometrial cancer: socioeconomic status and racial/ethnic differences in stage at diagnosis, treatment, and survival. Am J Public Health 94 (12): 2104-11, 2004.  [PUBMED Abstract]
    
    
17. Coates RJ, Click LA, Harlan LC, et al.: Differences between black and white patients with cancer of the uterine corpus in interval from symptom recognition to initial medical consultation (United States). Cancer Causes Control 7 (3): 328-36, 1996.  [PUBMED Abstract]
    
    

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