Risk Factors for Endometrial Cancer
Abstract & Commentary
By Rebecca H. Allen, MD, MPH, Assistant Professor, Department of Obstetrics and Gynecology, Warren Alpert Medical School of Brown University, Women and Infants Hospital, Providence, RI, is Associate Editor for OB/GYN Clinical Alert.
Dr. Allen reports no financial relationships relevant to this field of study.
Synopsis: In this case-control study, significant risk factors for the development of endometrial cancer after benign endometrial biopsy or dilation and curettage were lack of oral contraceptive pill use, endometrial polyps on the index sampling, personal history of nonpolyposis colorectal cancer-related malignancy, and body mass index of 35 or more.
Source: Torres ML, et al. Risk factors for developing endometrial cancer after benign endometrial sampling. Obstet Gynecol 2012;120:998-1004.
The authors performed a nested case-control study using data from the Rochester Epidemiology Project which conducts population-based studies of the residents of Olmsted County, Minnesota. They identified 90 women with endometrial cancer from January 1, 1970 to December 31, 2008 who had a benign endometrial biopsy or dilation and curettage (D&C) result prior to the diagnosis. Diagnoses included hyperplasia without atypia but not hyperplasia with atypia. Controls were selected from Olmsted County residents in the database who were aged 40-85 years and had a benign result from an endometrial biopsy or D&C along with no history of endometrial cancer or atypical hyperplasia. Controls were randomly selected, two for each case. Each control was matched for age and date when the endometrial biopsy or D&C occurred in addition to whether the index biopsy was benign or hyperplasia without atypia. Matched control group participants had at least as much follow-up as the cancer cases. The authors identified 172 controls, reporting that eight cancer cases were matched with only one instead of two controls.
Both case and control groups had a mean age of 51 years at the time of the index endometrial biopsy or D&C. The majority (65%) of cases and controls had a D&C for endometrial sampling. Median time to endometrial cancer diagnosis was 6.7 years. Women who underwent a D&C were 2.1 times more likely to be diagnosed later with endometrial cancer than women who had an endometrial biopsy (odds ratio [OR], 2.10; 95% confidence interval [CI], 1.08-4.12). There were similar numbers of women in each group whose index sampling diagnosis was endometrial hyperplasia without atypia: 19% of the cases and 22% of the controls. However, more cancer cases (22%) had polyps on endometrial biopsy or D&C than controls (5%, P < 0.001). On multivariable analysis, there were four variables associated with development of endometrial cancer: 1) oral contraceptive use before or at endometrial biopsy or D&C was protective (OR, 0.18; 95% CI, 0.08-0.45); 2) presence of polyp on histologic evaluation increased the risk of cancer (OR, 4.12; 95% CI, 1.40-12.17); 3) personal history of nonpolyposis colorectal cancer (HNPCC)-related malignancy increased the risk (OR, 4.44; 95% CI, 1.02-19.31); and 4) body mass index of 35 or more increased the risk (OR, 3.40; 95% CI, 1.18-9.78). The stage of endometrial cancer that developed in the case group was 90% stage 1, 3% stage 2, 6% stage 3, and 1% stage 4.
Commentary
The lifetime risk of endometrial cancer among women in the United States is 2.6%.1 In this study, investigators sought to identify risk or protective factors for the development of endometrial cancer in women who had a benign result on a previous endometrial biopsy or D&C. Knowledge of these risk factors may help target women for screening and prevention strategies. Obviously, women who undergo endometrial sampling are at high risk for the development of endometrial cancer because there was an indication for the biopsy in the first place. The risk factors that the authors identified are not new: obesity, lack of oral contraceptive pill use, HNPCC, and endometrial polyps. However, these findings will help identify women for more intensive surveillance after a benign result on endometrial sampling. The results also suggest that obese women, after a benign endometrial biopsy result, should be put on preventive therapy such as oral contraceptive pills, oral progestins, or the levonorgestrel IUD.
The age at which to sample the endometrium in women with abnormal uterine bleeding (AUB) is debated. When I trained as a resident, we were taught that any woman 35 years or older should be sampled if she had AUB because that is when the incidence of endometrial cancer begins to rise.1 Other sources2 put the cutoff at age 40 and American College of Obstetricians and Gynecologists (ACOG) now recommends age 45.3 Of course, any woman younger than that with risk factors for endometrial cancer such as chronic anovulation, obesity, tamoxifen use, diabetes, HNPCC, or family history of endometrial, ovarian, breast, or colon cancer also should have an endometrial biopsy.
In this study, more women underwent D&C than office endometrial biopsy, which may be due to the time the study was performed, which was before office endometrial biopsy was the standard sampling technique, and selection bias (e.g., patients at higher risk were taken for D&C rather than office endometrial biopsy). Office endometrial sampling devices have high accuracy in the diagnosis of endometrial cancer as long as the tissue sample is adequate.4 Office endometrial biopsy is used as a first-line test in women with AUB or other indications for endometrial sampling due to its low cost, high sensitivity, and ease of use. Because it is a blind sampling, however, if the pathology is focal, such as in a polyp, then pathology may be missed. Therefore, if the office endometrial biopsy result is insufficient or negative and the woman has persistent bleeding or has failed medical management of bleeding, then more evaluation needs to be done. ACOG recommends sonohysterogram or hysteroscopy to further evaluate the problem with a D&C to obtain endometrial tissue.3
References
- Howlader N, et al. SEER cancer statistics review, 1975-2009. National Cancer Institute. Bethesda, MD. Available at: http://seer.cancer.gov/csr/1975_2009_pops09/. Accessed Nov. 23, 2012.
- Feldman S. Evaluation of the endometrium for malignant or premalignant disease. UpToDate. October 2012. Available at: http://www.uptodate.com/contents/evaluation-of-the-endometrium-for-malignant-or-premalignant-disease. Accessed Nov. 24, 2012.
- Practice bulletin no. 128. Diagnosis of abnormal uterine bleeding in reproductive-aged women. Obstet Gynecol 2012;120:197-206.
- Clark TJ, et al. Accuracy of outpatient endometrial biopsy in the diagnosis of endometrial cancer: A systematic quantitative review. BJOG 2002;169:313-321.
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