Objective
There are known disparities in endometrial cancer survival with black women who experience a greater risk of death compared with white women. The purpose of this investigation was to evaluate the role of comorbid conditions as modifiers of endometrial cancer survival by race.
Study Design
Two hundred seventy-one black women and 356 white women who had been diagnosed with endometrial cancer from 1990-2005 were identified from a large urban integrated health center. A retrospective chart review was conducted to gather information on comorbid conditions and other known demographic and clinical predictors of survival.
Results
Black women experienced a higher hazard of death from any cause (hazard ratio [HR] 1.51; 95% confidence interval [CI], 1.22–1.87) and from endometrial cancer (HR, 2.42; 95% CI, 1.63–3.60). After adjustment for known clinical prognostic factors and comorbid conditions, the hazard of death for black women was elevated but no longer statistically significant for overall survival (HR, 1.22; 95% CI, 0.94–1.57), and the hazard of death from endometrial cancer remained significantly increased (HR, 2.27; 95% CI, 1.39–3.68). Both black and white women with a history of hypertension experienced a lower hazard of death from endometrial cancer (HR, 0.47; 95% CI, 0.23–0.98; and HR, 0.35; 95% CI, 0.19–0.67, respectively).
Conclusion
The higher prevalence of comorbid conditions among black women does not explain fully the racial disparities that are seen in endometrial cancer survival. The association between hypertension and a lower hazard of death from endometrial cancer is intriguing, and further investigation into the underlying mechanism is needed.
Endometrial cancer is the most common malignancy of the female genital tract and is the fourth leading cancer diagnosed in women, after breast, lung, and colon cancers. Incidence of endometrial cancer in the United States had been decreasing over the past 3 decades, but recent data show a reversal of that trend, with a 3.0% annual percentage increase from 2006-2010, compared with a negative 0.4% annual percentage change from 1997-2006. White women are at greater risk of the development of endometrial cancer than black women; however, black women are more likely to die of this disease. The lower survival rate among black women was identified decades ago, and this disparity has persisted over time. The mortality rate from endometrial cancer from 2006-2010 for black women was nearly twice the mortality rate of white women (7.4 vs 4.0 per 100,000). Although black women are diagnosed with less favorable histologic types, at more advanced stages, and with higher grade tumors than white women, poorer survival rates are still seen in black women for all stages, grades, and histologic types when compared with their white counterparts.
Reasons for these survival differences are likely due to a combination of factors that include differences in socioeconomic resources, environmental and behavioral risk factors, and tumor biology. One factor that has not been evaluated fully is the role comorbid conditions play in the racial disparity in endometrial cancer survival. Black women have a higher prevalence of obesity, diabetes mellitus, and hypertension. Although these conditions have been associated with poorer survival rates, a recent report with the use of Surveillance, Epidemiology, and End Results (SEER) Medicare data illustrated that comorbid conditions do not account fully for the racial disparity that is seen in endometrial cancer survival in a Medicare population. We sought to further evaluate the relationship between comorbid conditions and the racial disparity in endometrial cancer survival among women of all ages at a single institution.
Materials and Methods
After institutional review board approval was obtained, a case-only retrospective analysis of incident endometrial cancer cases (International Classification of Diseases [ICD]-O3 codes of C54.0-55.9) was conducted. Black and white women who were diagnosed from 1990-2005 were identified from the Henry Ford Health System (HFHS) tumor registry. The HFHS is a large, integrated health system in Detroit, MI. The HFHS currently consists of 5 hospitals, 36 ambulatory care facilities, and clinics (that offer free or low-cost care and are located throughout the metropolitan Detroit area) and serves patients of varying levels of socioeconomic and insurance status for both races. Clinical, demographic, risk factor, and survival data were obtained from 3 sources: the HFHS database, medical record abstraction, and the Metropolitan Detroit Cancer Surveillance System (MDCSS) registry, which is part of the National Cancer Institute’s Surveillance, Epidemiology and End Results program. The MDCSS ascertainment area encompasses the 3 county (Wayne, Oakland, and Macomb) metropolitan Detroit area, where the majority of patients at HFHS reside.
To standardize data collection, variables were abstracted from the medical record up to 5 years before the endometrial cancer diagnosis. Race information was self-reported and abstracted from the medical record. Comorbid conditions of interest included diabetes mellitus, hypertension, obesity (body mass index [BMI], ≥30 kg/m 2 ), morbid obesity (BMI, ≥40 kg/m 2 ), and a modified Charlson Comorbidity Index (CCI). The CCI is a weighed score of comorbid conditions that have been shown to predict death and was modified in this analysis to exclude diabetes mellitus (both complicated and uncomplicated), because that condition is an established risk factor for endometrial cancer and thus was evaluated separately. A condition was counted in the CCI if it was diagnosed before the endometrial cancer diagnosis. BMI was calculated from height and weight measurements in the medical record that were documented 2-5 years before diagnosis so that weight measures would not be influenced by any weight loss that was part of the disease process.
Information on known risk factors for endometrial cancer was also abstracted from the medical record. Smoking history was grouped into 3 categories: never smoker, former smoker, and current smoker. Reported parity was evaluated 2 ways: as a dichotomous variable (nulliparous vs parous) and as a categoric variable (nulliparous, 1-3 live births, and ≥4 live births). Histologic classification and grade information were reviewed by the HFHS pathologists (A.R.G. and D.S.) to standardize categorization. All cases were then rereviewed by a Wayne State University gynecologic pathologist (R.A.F.), and any discrepancy was resolved by consensus among the 3 pathologists (A.R.G., D.S., and R.A.F.). Histologic type was grouped into 4 categories: type I, type II, type III, and other. Type I included endometrioid and mucinous adenocarcinoma histologic types; type II included serous, clear cell, and mixed histologic types; type III included malignant mixed Müllerian tumors, and “other” included all other histologic types. Vital status information was obtained from the MDCSS database; follow-up information was obtained through the end of 2012.
Differences in age at diagnosis, International Federation of Gynecologists and Obstetricians stage, grade, histologic type, comorbid conditions, BMI before diagnosis, smoking history, and parity were examined by race. Racial differences in tumor characteristics were examined further, stratified by comorbid conditions. The differences in the distribution of these clinical and demographic variables were assessed with the use of χ 2 tests.
Log-rank tests and Cox proportional hazards models were used to assess the risk of overall and endometrial cancer–related deaths. Endometrial cancer–related deaths were defined by both the primary and underlying causes of death (ICD-9 codes I79 and I82 and ICD-10 code C54) that were recorded on the death certificate; survival time was calculated from the date of biopsy. Race-specific hazard ratios (HRs) and 95% confidence intervals (CIs) for overall and endometrial cancer–related survival were estimated for each comorbid condition and adjusted for known predictors of survival that were significant in univariate analyses. These predictor variables were age and year at diagnosis, International Federation of Gynecologists and Obstetricians stage, grade, histologic type, and treatment (surgery, chemotherapy, and radiation therapy). In addition, an interaction term with race and each comorbid condition was calculated. Overall and disease-specific hazard of death was estimated for black women, as compared with white women, and then estimated after adjustment with the use of 2 different models. Model 1 was adjusted for year and age of diagnosis, receipt of surgery, chemotherapy, radiation therapy, and tumor characteristics (stage, grade, and histologic type). Model 2 was adjusted with all the variables listed for model 1 and comorbid conditions (diabetes mellitus, hypertension, obesity, and CCI). These analyses were repeated in the subset of women who were treated surgically. All analyses were performed with SAS statistical software (version 9.2; SAS Institute Inc, Cary, NC).
Results
A total of 627 women, 271 black women (43%) and 356 white women (57%), were identified for inclusion in this study. Compared with their white counterparts, black women were more likely to have aggressive disease phenotypes with higher proportions of type II/III histologic types and higher grade tumors and were more likely to be diagnosed at a later stage of disease (all P < .001). Black women were less likely to receive surgical treatment (17% vs 4%; P < .001) and more likely to receive chemotherapy ( P = .041). Black women were more likely to be diagnosed with hypertension ( P < .001) and to be obese ( P < .001). CCI ( P = .305) and the diagnosis of diabetes mellitus ( P = .086) were similar in black and white women with endometrial cancer ( Table 1 ). The significant racial differences that were seen in histologic type and grade persisted when they were examined by either the presence or absence of diabetes mellitus, obesity, hypertension, or other comorbid conditions ( Table 2 ).
| Variable | White (n = 356) | Black (n = 271) | P value a | ||
|---|---|---|---|---|---|
| n | % | n | % | ||
| Age at diagnosis, y | .204 | ||||
| <50 | 49 | 14 | 32 | 12 | |
| 50-59 | 71 | 20 | 39 | 14 | |
| 60-69 | 112 | 31 | 99 | 37 | |
| 70+ | 124 | 35 | 101 | 37 | |
| International Federation of Gynecologists and Obstetricians stage | < .001 | ||||
| I | 246 | 69 | 142 | 52 | |
| II | 40 | 11 | 32 | 12 | |
| III | 40 | 11 | 37 | 14 | |
| IV | 19 | 5 | 45 | 17 | |
| Unknown | 11 | 3 | 15 | 6 | |
| Grade | < .001 | ||||
| I | 189 | 53 | 79 | 29 | |
| II | 67 | 19 | 35 | 13 | |
| III | 91 | 26 | 135 | 50 | |
| Unknown | 9 | 3 | 22 | 8 | |
| Histologic group | < .001 | ||||
| Type I | 260 | 73 | 148 | 55 | |
| Type II | 67 | 19 | 84 | 31 | |
| Type III | 24 | 7 | 33 | 12 | |
| Other | 5 | 1 | 6 | 2 | |
| Modified Charlson comorbidity score | .305 | ||||
| None | 208 | 58 | 140 | 52 | |
| 1 | 64 | 18 | 55 | 20 | |
| ≥2 | 84 | 24 | 73 | 27 | |
| Unknown | 0 | 0 | 3 | 1 | |
| Hypertension | < .001 | ||||
| No | 151 | 42 | 65 | 24 | |
| Yes | 205 | 58 | 206 | 76 | |
| Diabetes mellitus | .086 | ||||
| No | 275 | 77 | 193 | 71 | |
| Yes | 81 | 23 | 78 | 29 | |
| Body mass index, kg/m 2 | < .001 | ||||
| <25 | 66 | 19 | 31 | 11 | |
| 25-29.9 | 91 | 26 | 38 | 14 | |
| 30-39.9 | 108 | 30 | 119 | 44 | |
| ≥40 | 76 | 21 | 74 | 27 | |
| Unknown | 15 | 4 | 9 | 3 | |
| Smoking history | .590 | ||||
| Nonsmoker | 223 | 63 | 182 | 67 | |
| Current | 47 | 13 | 30 | 11 | |
| Former | 75 | 21 | 55 | 20 | |
| Unknown | 11 | 3 | 4 | 1 | |
| Nulliparity | .004 | ||||
| No | 264 | 74 | 218 | 80 | |
| Yes | 85 | 24 | 38 | 14 | |
| Unknown | 7 | 2 | 15 | 6 | |
| Parity | < .001 | ||||
| None | 85 | 24 | 38 | 14 | |
| 1-3 | 186 | 52 | 126 | 46 | |
| ≥4 | 77 | 22 | 92 | 34 | |
| Unknown | 8 | 2 | 15 | 6 | |
| Surgery | < .001 | ||||
| No | 14 | 4 | 45 | 17 | |
| Yes | 342 | 96 | 226 | 83 | |
| Radiation therapy | .686 | ||||
| No | 225 | 63 | 167 | 62 | |
| Yes | 131 | 37 | 104 | 38 | |
| Chemotherapy | .041 | ||||
| No | 286 | 80 | 199 | 73 | |
| Yes | 70 | 20 | 72 | 27 | |
| Vital Status | < .001 | ||||
| Alive | 164 | 46 | 100 | 37 | |
| Deceased | |||||
| Endometrial cancer | 43 | 12 | 66 | 24 | |
| Other reason | 149 | 42 | 105 | 39 | |
| Variable | Comorbid condition | |||||
|---|---|---|---|---|---|---|
| Absent | Present | |||||
| White women, % | Black women, % | P value | White women, % | Black women, % | P value | |
| Diabetes mellitus | ||||||
| Total, n | 275 | 193 | 81 | 78 | ||
| Histologic group | < .001 | .051 | ||||
| Type I | 75 | 56 | 73 | 56 | ||
| Type II | 20 | 31 | 16 | 32 | ||
| Type III | 6 | 13 | 11 | 12 | ||
| Grade | < .001 | .007 | ||||
| I | 55 | 31 | 53 | 33 | ||
| II | 19 | 14 | 19 | 13 | ||
| III | 26 | 55 | 28 | 53 | ||
| International Federation of Gynecologists and Obstetricians stage | < .001 | .040 | ||||
| I | 71 | 57 | 71 | 51 | ||
| II | 13 | 12 | 8 | 14 | ||
| III | 11 | 14 | 13 | 15 | ||
| IV | 5 | 16 | 8 | 21 | ||
| Obesity | ||||||
| Total, n | 157 | 69 | 184 | 193 | ||
| Histologic group | .001 | .006 | ||||
| Type I | 74 | 50 | 73 | 58 | ||
| Type II | 20 | 32 | 19 | 32 | ||
| Type III | 6 | 18 | 8 | 10 | ||
| Grade | < .001 | < .001 | ||||
| I | 54 | 22 | 58 | 36 | ||
| II | 19 | 13 | 19 | 15 | ||
| III | 27 | 65 | 24 | 49 | ||
| International Federation of Gynecologists and Obstetricians stage | .012 | .004 | ||||
| I | 74 | 52 | 69 | 60 | ||
| II | 8 | 15 | 15 | 12 | ||
| III | 12 | 21 | 12 | 11 | ||
| IV | 6 | 12 | 5 | 17 | ||
| Hypertension | ||||||
| Total, n | 151 | 65 | 205 | 206 | ||
| Histologic group | .116 | .001 | ||||
| Type I | 77 | 63 | 72 | 54 | ||
| Type II | 16 | 26 | 22 | 34 | ||
| Type III | 7 | 11 | 6 | 13 | ||
| Grade | .004 | < .001 | ||||
| I | 53 | 31 | 56 | 32 | ||
| II | 21 | 19 | 18 | 13 | ||
| III | 26 | 50 | 26 | 56 | ||
| International Federation of Gynecologists and Obstetricians stage | .001 | .003 | ||||
| I | 72 | 54 | 71 | 56 | ||
| II | 12 | 10 | 12 | 13 | ||
| III | 10 | 10 | 13 | 16 | ||
| IV | 6 | 26 | 5 | 15 | ||
| Other comorbid conditions | ||||||
| Total, n | 208 | 140 | 148 | 128 | ||
| Histologic group | .003 | .001 | ||||
| Type I | 75 | 58 | 73 | 52 | ||
| Type II | 19 | 36 | 19 | 28 | ||
| Type III | 6 | 7 | 8 | 19 | ||
| Grade | .003 | < .001 | ||||
| I | 48 | 35 | 64 | 28 | ||
| II | 21 | 16 | 16 | 12 | ||
| III | 31 | 49 | 20 | 60 | ||
| International Federation of Gynecologists and Obstetricians stage | .196 | < .001 | ||||
| I | 71 | 64 | 72 | 47 | ||
| II | 12 | 12 | 10 | 14 | ||
| III | 10 | 11 | 13 | 19 | ||
| IV | 6 | 13 | 5 | 21 | ||
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