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Endometrial Cancer Screening (PDQ®)

Health Professional Version
Last Modified: 02/26/2014

Significance

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 52,630 new cases expected to occur in 2014 and an estimated 8,590 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. From 2006 to 2010, incidence rates of endometrial cancer increased by 1.5% per year in women younger than 50 years and increased by 2.6% in women 50 years and older. During that same time frame, the endometrial cancer mortality rates increased by 1.5% in women younger than 50 years and remained stable in women 50 years and older.[1] 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.[4-8] 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).[10-12] 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 in 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 2014. Atlanta, Ga: American Cancer Society, 2014. Available online. Last accessed March 26, 2014. 

  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 December 13, 2013. 

  3. Jick H, Walker AM, Rothman KJ: The epidemic of endometrial cancer: a commentary. Am J Public Health 70 (3): 264-7, 1980.  [PUBMED Abstract]

  4. 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]

  5. 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]

  6. Heiss G, Wallace R, Anderson GL, et al.: Health risks and benefits 3 years after stopping randomized treatment with estrogen and progestin. JAMA 299 (9): 1036-45, 2008.  [PUBMED Abstract]

  7. Doherty JA, Cushing-Haugen KL, Saltzman BS, et al.: Long-term use of postmenopausal estrogen and progestin hormone therapies and the risk of endometrial cancer. Am J Obstet Gynecol 197 (2): 139.e1-7, 2007.  [PUBMED Abstract]

  8. Barakat RR, Bundy BN, Spirtos NM, et al.: Randomized double-blind trial of estrogen replacement therapy versus placebo in stage I or II endometrial cancer: a Gynecologic Oncology Group Study. J Clin Oncol 24 (4): 587-92, 2006.  [PUBMED Abstract]

  9. Cuzick J, Forbes JF, Sestak I, et al.: Long-term results of tamoxifen prophylaxis for breast cancer--96-month follow-up of the randomized IBIS-I trial. J Natl Cancer Inst 99 (4): 272-82, 2007.  [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]