Endometrial Cancer Mortality Research Articles

Addressing the Role of Obesity in Endometrial Cancer Risk, Prevention, and Treatment.

In sharp contrast to many other cancer types, the incidence and mortality of endometrial cancer continue to grow. This unfortunate trend is, in no small part, a result of the worldwide obesity epidemic. More than half of endometrial cancers are currently attributable to obesity, which is recognized as an independent risk factor for this disease. In this review, we identify the molecular mechanisms by which obesity and adipose tissue contribute to the pathogenesis of endometrial cancer. We further discuss the impact of obesity on the clinical management of the disease and examine the development of rational behavioral and pharmaceutical interventions aimed at reducing endometrial cancer risk, improving cancer outcomes, and preserving fertility in an increasingly younger population of patients with endometrial cancer.

Racial disparities impact on endometrial cancer recurrence.

e17111Background: The relationship of race and endometrial cancer (EC) outcomes is controversial. Published literature documents that EC mortality is 2.5 times more likely in African Americans (AA)...

Abstract C29: Racial disparities in endometrial cancer epidemiology and mortality-to-incidence ratios in South Carolina

Abstract Background: Endometrial cancer (EC) exhibit striking racial disparities with higher mortality in African Americans (AA) compared to European Americans (EA). The mortality-to-incidence rate ratio (MIR) gives a population based measure for survival which accounts for incidence. The objective of this study was to map EC MIRs by race for eight health regions within South Carolina (SC) and chart EC incidence by race and grade across the four cancer stages. Methods: Data on EC incidence and deaths were obtained from the South Carolina Central Cancer Registry, and Vital Registry respectively to construct MIRs. ArcGIS 10.1 software was used to map EC MIRs by race for eight health regions within South Carolina. Four classes of MIR were derived using the national MIR for EC among EAs as the reference. Results: When stratified by tumor stage, AAs had higher levels of poorly differentiated tumors across all stages. The incidence and mortality were consistently higher among AAs. Striking racial differences were observed with incidence and mortality consistently higher among AAs. In all eight health regions, AAs were in the highest MIR category. By contrast, EA MIRs were more evenly represented over the 4 classes. Conclusions: The MIR proved useful for identifying disparities in EC incidence, mortality and virulence among AA and EA women in SC. Cancer surveillance programs may use the MIR to monitor disparities across racial/ethnic groups and geographic regions going forward. MIRs have the potential to serve as an indicator of the long-term success of cancer surveillance programs. Citation Format: Oluwole Adeyemi Babatunde, Swann Arp Adams, Jan M. Eberth, Michael D. Wirth, Seul Ki Choi, James R. Hebert. Racial disparities in endometrial cancer epidemiology and mortality-to-incidence ratios in South Carolina. [abstract]. In: Proceedings of the Eighth AACR Conference on The Science of Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; Nov 13-16, 2015; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2016;25(3 Suppl):Abstract nr C29.

Racial disparities in endometrial cancer mortality-to-incidence ratios among Blacks and Whites in South Carolina.

Endometrial cancer (EC) exhibits striking racial disparities with higher mortality in Blacks compared to Whites. The mortality-to-incidence ratio (MIR) provides a population-based measure of survival which accounts for incidence. The objective of this study was to map EC MIRs by race for eight health regions within South Carolina (SC) and chart EC incidence by race and grade across the four cancer stages. Cancer incidence and mortality data were obtained from the SC Community Access Network (SCAN), the online data query system provided by the SC Department of Health and Environmental Control (DHEC). The underlying data for SCAN were generated from the SC Central Cancer Registry and SC DHEC Vital Records and used to construct MIRs. ArcGIS 10.1 was used to map EC MIRs by race for eight health regions within SC. Four categories of MIR were derived using the national MIR for EC among Whites as the reference category. Blacks had higher levels of poorly differentiated tumors across all stages and higher incidence and mortality rates. In all eight health regions, Blacks were in the highest MIR category. By contrast, the MIRs for Whites were more evenly represented over the four categories. The MIR proved useful for identifying disparities in EC incidence and mortality among Black and White women in SC. Cancer surveillance programs may use the MIR to monitor disparities across racial/ethnic groups and geographic regions going forward. MIRs have the potential to serve as an indicator of the long-term success of cancer surveillance programs.

Obesity and Endometrial Cancer.

Endometrial cancer is the sixth most common cancer in women worldwide and the most common gynecologic malignancy in the developed world. This chapter explores the current epidemiologic evidence on the association between obesity and endometrial cancer risk and mortality. Using body mass index (BMI) as a measure of obesity, we found that obesity (defined as BMI >30 and <35kg/m2) was associated with a 2.6-fold increase in endometrial cancer risk, while severe obesity (BMI>35kg/m2) was associated with a 4.7-fold increase compared to normal-weight women (BMI<25kg/m2). Increased central adiposity also increased endometrial cancer risk by 1.5- to twofold. Among both healthy and endometrial cancer patient populations, obesity was associated with a roughly twofold increase in endometrial cancer-specific mortality. This risk reduction was also observed for obesity and all-cause mortality among endometrial cancer patients. In the few studies that assessed risk associated with weight change, an increased endometrial cancer risk with weight gain and weight cycling was observed, whereas some evidence for a protective effect of weight loss was found. Furthermore, early-life obesity was associated with a moderately increased risk of endometrial cancer later in life. There are several mechanisms whereby obesity is hypothesized to increase endometrial cancer risk, including increased endogenous sex steroid hormones, insulin resistance, chronic inflammation and adipokines. Further research should focus on histological subtypes or molecular phenotypes of endometrial tumors and population subgroups that could be at an increased risk of obesity-associated endometrial cancer. Additionally, studies on weight gain, loss or cycling and weight loss interventions can provide mechanistic insight into the obesity-endometrial cancer association. Sufficient evidence exists to recommend avoiding obesity to reduce endometrial cancer risk.

Intraperitoneal Fat through GRP78: A Risk Factor for Endometrial Cancer.

Introduction. The identification of biological markers that indicate an increased risk for the development or recurrence of endometrial cancer (EC) in obese women might be useful for decreasing EC mortality and morbidity. Glucose-regulated protein 78 (GRP78) is a major protein of the endoplasmic reticulum expressed in all normal cells. Overexpression of GRP78 has been reported to be a tumoral biomarker. Increased detection of GRP78 is positively correlated with the tumoral stage and prognosis. This study aimed to identify a correlation between intraperitoneal fat, plasma GRP78 levels, and EC. Materials and Methods. Two groups of patients were included in the study: group I, 44 patients diagnosed with EC, and group II, 44 patients without gynecological pathology or inflammatory disorders. Visceral fat was determined by ultrasound and plasma GRP78 levels were measured. Results. Plasma GRP78 levels were significantly higher in patients with EC compared to the control group. Intraperitoneal fat was in a positive linear correlation with the plasma GRP78 level (p < 0.0001). Conclusion. The measurement of the GRP78 level associated with the determination of intraperitoneal fat can be a useful predictor for EC.

Continuous Combined Estrogen Plus Progestin and Endometrial Cancer: The Women’s Health Initiative Randomized Trial

While progestin addition to estrogen mitigates endometrial cancer risk, the magnitude of the effect on incidence, specific endometrial cancer histologies, and endometrial cancer mortality remains unsettled. These issues were assessed by analyses after extended follow-up of the Women's Health Initiative (WHI) randomized clinical trial evaluating continuous combined estrogen plus progestin use. The WHI enrolled 16 608 postmenopausal women into a randomly assigned, double-blind, placebo-controlled trial. Women age 50 to 79 years with intact uteri with normal endometrial biopsy at entry were randomly assigned to once-daily 0.625 mg conjugated equine estrogen plus 2.5mg medroxyprogesterone acetate (n = 8506) as a single pill or matching placebo (n = 8102). Follow-up beyond the original trial completion date required reconsent, obtained from 12 788 (83%) of surviving participants. Analyses were by intent-to-treat. All statistical tests were two-sided. After 5.6 years' median intervention and 13 years' median cumulative follow-up, there were fewer endometrial cancers in the combined hormone therapy compared with the placebo group (66 vs 95 case patients, yearly incidence, 0.06% vs 0.10%; hazard ratio [HR] = 0.65, 95% confidence interval [CI] = 0.48 to 0.89, P = .007). While there were somewhat fewer endometrial cancers during intervention (25 vs 30, respectively; HR = 0.77, 95% CI = 0.45 to 1.31), the difference became statistically significant postintervention (41 vs 65, respectively; HR = 0.59, 95% CI = 0.40 to 0.88, P = .008), but hazard ratios did not differ between phases (P difference = .46). There was a statistically nonsignificant reduction in deaths from endometrial cancer in the estrogen plus progestin group (5 vs 11 deaths, HR = 0.42, 95% CI = 0.15 to 1.22). In postmenopausal women, continuous combined estrogen plus progestin decreases endometrial cancer incidence.

Abstract B62: Racial disparities in endometrial cancer incidence and mortality are limited to non-Hispanic black women

Abstract Background: Unlike the decreasing incidence seen for most cancers, incidence rates of endometrial cancer have been increasing in the United States over the last decade. Earlier studies have shown that mortality rates from endometrial cancer are significantly higher for non-Hispanic black women compared to non-Hispanic white women, but this has not been established for other racial/ethnic groups. Our objective was to determine whether the increasing incidence and mortality from endometrial cancer are equally distributed by race/ethnicity and tumor histologic subtype. Methods: Data from the Surveillance, Epidemiology and End Results (SEER) registry were used to identify women diagnosed with endometrial cancer from 2000-2011. A total of 120,513 women, including 90,621 non-Hispanic white (NHW) women (75.2%), 11,386 Hispanic women (9.4%), 10,365 non-Hispanic black women (NHB) (8.6%) and 8,141 Asian women (6.8%) comprised the study population. Age-adjusted incidence and incidence-based mortality rates, with 95% confidence intervals and annual percent changes (APC), were calculated by race/ethnicity (4 groups) overall and for 7 histologic subtypes (low grade endometrioid, high grade endometrioid, clear cell, mixed, MMMT, serous, and other), along with rate ratios to compare racial/ethnic groups, using NHW as the referent group. In addition, 5-year survival rates were calculated by race/ethnic group, histologic subtype, and stage at diagnosis (localized, regional, distant). Differences between NHW and NHB women in the percentage surviving 5 years were described by calculating (%NHW-%NHB)/%NHW) overall and for each histologic subtype and each stage at diagnosis (21 comparisons). Results: Incidence rates for endometrial cancers are rising across all racial/ethnic groups, with the greatest annual percent change (APC) seen among NHB and Asian women (APC=2.5 for both). Low-grade endometrioid endometrial cancers are the most commonly diagnosed subtype among all women, with highest rates in NHW women, but these rates have stabilized or decreased over the last decade for all women with the exception of NHB women (APC=1.0). High grade endometrioid endometrial cancers have significantly decreased incidence rates over the last decade, particularly among NHW women (APC=-2.5). NHB women have the highest incidence rates of this and other aggressive subtypes of endometrial cancers (clear cell, serous, and malignant mixed Mullerian tumors) compared to NHW women. Hispanic and Asian women had incidence rate ratios equal to or lower than NHW women for all tumor subtypes. For every subtype and stage of disease, the 5-year survival for NHB women is lower than for NHW women, and significantly lower for nearly each comparison. The smallest percent difference seen is for women with localized endometrioid cancers, where NHB women have 6% lower survival, and the largest is 59% lower survival for distant stage clear cell cancers. Hispanic and Asian women have the same or slightly better survival rates compared to NHW women across all stages and subtypes. Conclusions: The lower survival rates among NHB women with endometrial cancer persist at nearly every stage and histologic subtype examined. Various factors, including socioeconomic status (SES), comorbid conditions, access to care, and treatment decisions may all impact this disparity to some extent, yet Hispanic women who have many of the same challenges are at lower risk of occurrence and have outcomes similar to NHW women after diagnosis. Additionally, the most aggressive types of endometrial cancer are also more common among NHB women, and are among the endometrial cancer subtypes with largest increasing incidence rates. We have yet to fully account for these disparities seen primarily in NHB women and, without intervention, they are likely to persist and potentially widen as endometrial cancer emerges as a significant cause of morbidity and mortality in the decades to come. Citation Format: Michele L. Cote, Julie J. Ruterbusch, Sara H. Olson, Karen H. Lu, Rouba Ali-Fehmi. Racial disparities in endometrial cancer incidence and mortality are limited to non-Hispanic black women. [abstract]. In: Proceedings of the Seventh AACR Conference on The Science of Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; Nov 9-12, 2014; San Antonio, TX. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2015;24(10 Suppl):Abstract nr B62.

The Growing Burden of Endometrial Cancer: A Major Racial Disparity Affecting Black Women.

In contrast with the decreasing incidence seen for most cancers, endometrial cancer has been increasing in the United States. We examined whether the increasing incidence and mortality from endometrial cancer are equally distributed by race/ethnicity and tumor histologic subtype. Surveillance, Epidemiology, and End Results (SEER) endometrial cancer incidence and mortality data were obtained from 2000 to 2011. Age-adjusted incidence and incidence-based mortality rates, 95% confidence intervals, and annual percent changes (APC) were calculated. Rate ratios were calculated to compare racial/ethnic groups. Five-year relative survival rates were presented to explore survival by stage at diagnosis. Incidence rates for endometrial cancers are rising across all racial/ethnic groups, with the greatest APC seen among non-Hispanic black (NHB) and Asian women (APC, 2.5 for both). NHB women have significantly higher incidence rates of aggressive endometrial cancers (clear cell, serous, high-grade endometrioid, and malignant mixed Mullerian tumors) compared with non-Hispanic white (NHW) women. Hispanic and Asian women have incidence rates equal to or lower than NHW women for all tumor subtypes. For nearly every stage and subtype, the 5-year relative survival for NHB women is significantly less than NHW women, whereas Hispanic and Asian women have the same or better survival. Endometrial cancer incidence is increasing for all women, particularly the aggressive subtypes. The disparity associated with excess incidence for these aggressive histologic subtypes and poorer survival is limited to NHB women. Increasing rates of aggressive endometrial cancers may widen the survival disparity between NHW and NHB women.

Abstract 882: Obesity, comorbidity and endometrial cancer survival: the multiethnic cohort

Abstract Background: Endometrial cancer (EC) is the most common gynecologic cancer diagnosed in the United States. With &amp;gt;750,000 survivors in 2014, EC comprises the second largest group of female cancer survivors. Higher body mass index (BMI) and other medical comorbidities have been suggested to negatively impact EC survival; however, data in minority populations with rising EC incidence and mortality (i.e. Asian Americans, African Americans, Latinas, etc.) are scarce. We examined the association of pre-diagnostic BMI and obesity-related comorbidities with overall survival in African-American, Japanese, Native Hawaiian, Latino and white women in the Multiethnic Cohort. Methods: Women with complete risk factor data who developed endometrial cancer during follow up were included in the analysis (N = 998). BMI and obesity-related comorbidities (diabetes, hypertension, heart attack and stroke) were self-reported at cohort entry and at subsequent follow-ups. Cox's models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) with time-varying exposures in relation to all-cause mortality while adjusting for age at diagnosis, tumor characteristics, treatment, and education. Results: The mean age at EC diagnosis was 67.7 ± 8.5 years. The mean follow-up period was 7.3 ± 5.3 years from diagnosis to death or end of follow up during which time a total of 323 deaths were observed, 84 (26%) of which were due to EC. The mean BMI was 29.9 kg/m2 and 53% of women had at least one comorbid condition. The prevalence of obesity and comorbid conditions varied across ethnic groups (P&amp;lt;0.0001). The prevalence of obesity (BMI ≥30 kg/m2) ranged from 18% in Japanese Americans to 69% in Hawaiians. The prevalence of women with at least one comorbid condition ranged from 38% in whites to 76% in African Americans. Women with a BMI ≥35 kg/m2 had an increased risk of all-cause mortality [HR = 1.55 (95% CI: 1.06, 2.28)] compared with women with BMI &amp;lt;25 kg/m2. Women with two or more comorbid conditions also had a higher risk of all-cause mortality (HR = 1.61; 95% CI: 1.12, 2.31) compared to those with no medical comorbidities. There was evidence of ethnic differences in the comorbidity and all-cause mortality association (P interaction = 0.02); the presence of two or more comorbidities was significantly associated with all-cause mortality in whites (HR = 2.98; 95% CI: 1.34, 6.63) and Japanese Americans (HR = 3.47; 95% CI: 1.19, 10.14), but not in African Americans (HR = 0.88; 95% CI: 0.42, 1.82), Latinas (HR = 1.16; 95% CI: 0.45, 2.96), and Native Hawaiians (HR = 0.95; 95% CI: 0.22, 4.02). Conclusions: Our results show that higher pre-diagnosis BMI and the presence of two or more comorbidities increase the risk of overall death among multiethnic women diagnosed with EC. Clear identification and targeted managements of these conditions may improve overall survival after EC diagnosis. Citation Format: Veronica Wendy Setiawan, Gertraud Maskarinec, Yvonne G. Lin, Dongyun Yang, Lynne R. Wilkens, Brian E. Henderson, Loic Le Marchand. Obesity, comorbidity and endometrial cancer survival: the multiethnic cohort. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 882. doi:10.1158/1538-7445.AM2015-882

Endometrial and cervical cancer: incidence and mortality among women in the Lodz region

IntroductionBy the early 21st century the most common cancer of female genitals in Poland was cervical cancer. Now endometrial cancer ranks first. The aim of this study was to analyse the incidence and mortality of endometrial and cervical cancer among women in the Lodz region.Material and methodsData on the incidence and mortality of endometrial and cervical cancer among inhabitants of the Lodz region were obtained from the National Cancer Registry and Bulletin of Cancer Cases in the Lodz region. The analysis covered ten consecutive years beginning in 2001.ResultsThe number of new cases reported in 2010 exceeded that observed in 2001 by 181. The standardized incidence rate of endometrial cancer increased by 6.3, while the standardized incidence rate of cervical cancer decreased by 1.4.ConclusionsIn the years 2001-2010, the incidence of endometrial cancer increased by 88.3% and that of cervical cancer decreased by 6.5% among inhabitants of the Lodz region. In the years 2001-2010, mortality of endometrial cancer increased by 24.5% and that of cervical cancer decreased by 12.6%. In 2010, the highest crude incidence rates in the Lodz region of both endometrial and cervical cancer at 39.1 were recorded in the district town of Piotrków.

Abstract 4140: Secular trends in incidence and mortality of female cancers in Shanghai, China (1973-2009)

Abstract Socioeconomic development and urbanization have resulted in dramatic changes in cancer incidence and mortality in China. As one of the largest and most developed cities in China, Shanghai's cancer rates reflect the changing burden of cancer in China. This study was undertaken to evaluate trends and quantify changes in the incidence and mortality of breast, ovarian, endometrial, and cervical cancers among female residents of urban Shanghai from 1973 to 2009. Data on cancer incidence and mortality were collected by the Shanghai Cancer Registry. International Classification of Disease version 10 codes for breast (C50), cervical (C53), endometrial (corpus uteri and uterus unspecified; C54 and C55), and ovarian cancer (C56) were included in the current analysis. Annual population data was provided by the Department of Vital Statistics, Shanghai Municipal Center for Disease Control and Prevention. A total of 73,755 female cancers and 28,274 related deaths were documented between 1973 and 2009. Age-standardized incidence and mortality rates were calculated using the Segi/Doll 1960 world standard. Joinpoint regression models were used to fit joined straight lines on a log-scale for annual age-standardized rates and to calculate annual percent changes (APC). Between 1973 and 2009, the incidence of breast, ovarian, and endometrial cancers increased, with overall APCs of 2.93, 2.20, and 1.66, respectively. Significant trends were found for breast cancer between 1979 and 1998 (APC 3.07) and for ovarian cancer between 1983 and 2009 (APC 2.83). For endometrial cancer a significant decrease occurred from 1973 to 1983 (APC -4.27), followed by a significant increase from 1983 to 1996 (APC 2.58). The incidence of cervical cancer decreased, with an overall APC of -3.91; this included three significant decreasing trends between 1973 and 1996, followed by a significant increase through 2009 (APC 8.49). The mortality of breast and ovarian cancers increased, with overall APCs of 0.70 and 0.58, respectively. Significant trends were found for breast cancer between 1982 and 2004 (APC 1.55) and for ovarian cancer during the entire time period. The mortality of cervical and endometrial cancers decreased, with overall APCs of -5.36 and -2.33, respectively. For cervical cancer, this included a significant decrease between 1973 and 1999 (APC -7.34), followed by a significant increase through 2009 (APC 3.24). For endometrial cancer, this included a significant decrease between 1973 and 1988 (APC -5.59). In summary, increasing trends were found for breast, ovarian and endometrial cancer incidence, and for breast and ovarian cancer mortality, while decreasing trends were found for cervical cancer incidence and cervical and endometrial cancer mortality among women in urban Shanghai. Additional analyses to identify age-period-cohort effects in this data are underway. This study lays the ground work for the establishment of cancer prevention and control priorities in China. Citation Format: Zhezhou Huang, Alicia C. Beeghly-Fadiel, Ying Zheng, Wanqing Wen, Yutang Gao, Chunxiao Wu, Pingping Bao, Weijian Zhong, Fan Jin, Yongbing Xiang, Wei Zheng, Xiao Ou Shu, Wei Lu. Secular trends in incidence and mortality of female cancers in Shanghai, China (1973-2009). [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4140. doi:10.1158/1538-7445.AM2014-4140

Validated Competing Event Model for the Stage I-II Endometrial Cancer Population

Early-stage endometrial cancer patients are at higher risk of noncancer mortality than of cancer mortality. Competing event models incorporating comorbidity could help identify women most likely to benefit from treatment intensification. 67,397 women with stage I-II endometrioid adenocarcinoma after total hysterectomy diagnosed from 1988 to 2009 were identified in Surveillance, Epidemiology, and End Results (SEER) and linked SEER-Medicare databases. Using demographic and clinical information, including comorbidity, we sought to develop and validate a risk score to predict the incidence of competing mortality. In the validation cohort, increasing competing mortality risk score was associated with increased risk of noncancer mortality (subdistribution hazard ratio [SDHR], 1.92; 95% confidence interval [CI], 1.60-2.30) and decreased risk of endometrial cancer mortality (SDHR, 0.61; 95% CI, 0.55-0.78). Controlling for other variables, Charlson Comorbidity Index (CCI) = 1 (SDHR, 1.62; 95% CI, 1.45-1.82) and CCI >1 (SDHR, 3.31; 95% CI, 2.74-4.01) were associated with increased risk of noncancer mortality. The 10-year cumulative incidences of competing mortality within low-, medium-, and high-risk strata were 27.3% (95% CI, 25.2%-29.4%), 34.6% (95% CI, 32.5%-36.7%), and 50.3% (95% CI, 48.2%-52.6%), respectively. With increasing competing mortality risk score, we observed a significant decline in omega (ω), indicating a diminishing likelihood of benefit from treatment intensification. Comorbidity and other factors influence the risk of competing mortality among patients with early-stage endometrial cancer. Competing event models could improve our ability to identify patients likely to benefit from treatment intensification.

Cause-Specific Effects of Radiotherapy and Lymphadenectomy in Stage I–II Endometrial Cancer: A Population-Based Study

Radiotherapy and lymphadenectomy have been associated with improved survival in population-based studies of endometrial cancer, which is in contrast with findings from randomized trials and meta-analyses. The primary study aim was to estimate the cause-specific effects of adjuvant radiotherapy and lymphadenectomy on competing causes of mortality. We analyzed Surveillance, Epidemiology, and End Results (SEER) data from 1988 to 2006. The sample comprised 58172 patients with stage I and II endometrial adenocarcinoma. Patients were risk stratified by stage, grade, and age. Cumulative incidences and cause-specific hazards of competing causes of mortality were estimated according to treatment. All statistical tests were two-sided. Pelvic radiotherapy was associated with statistically significantly increased endometrial cancer mortality (hazard ratio [HR] = 1.66; 95% confidence interval [CI] = 1.52 to 1.82) in all stage I and II patients and decreased noncancer mortality in intermediate and high-risk stage I and II patients (HR = 0.82; 95% CI = 0.77 to 0.89). Lymphadenectomy was associated with increased endometrial cancer mortality in stage I patients (HR = 1.27; 95% CI = 1.16 to 1.39), decreased endometrial cancer mortality in stage II patients (HR = 0.61; 95% CI = 0.52 to 0.72), and decreased noncancer mortality in both stage I and II patients (HR = 0.84; 95% CI = 0.80 to 0.88). Effects of radiotherapy and lymphadenectomy on second cancer mortality varied according to risk strata. Radiotherapy and lymphadenectomy are associated with statistically significantly reduced noncancer mortality in stage I and II endometrial cancer. The improved overall survival associated with these treatments reported from SEER studies is largely attributable to their selective application in healthier patients rather than their effects on endometrial cancer.

Abstract LB-26: Biomarker changes in the endometrium of morbidly obese women undergoing bariatric surgery: Implications for endometrial cancer risk reduction.

Abstract Introduction: With increasing obesity rates in the US and around the world, both endometrial cancer morbidity and mortality are on the rise. The objectives of this study were to observe changes occurring in several biomarkers in the endometrium of asymptomatic morbidly obese women pre and post bariatric surgery, with the hypothesis that some of the premalignant changes may be normalized with weight loss. Methods: Endometrial samples were obtained from obese women at the time of roux en y gastric bypass bariatric surgery and one year following the surgery. Both investigators and pathologists were blinded to the status of patients until the conclusion of the study. All endometrial biopsies were subjected to immunohistochemical stains for hormone receptors, Estrogen (ER), Progesterone (PR) and Androgen (AR) along with stains for CD3, CD20, COX 2,and Ki-67 using standard immunohistochemistry protocols. Hormone receptor status was expressed using H score. Paired T-tests and non-parametric Wilcoxon signed-rank test was performed to compare the changes for ER, PR, and AR expression before and after the surgery. The exact McNemar/Bowker tests of symmetry were performed to compare proportions between categories for matched pairs (pre and post treatment) for CD3, CD20, COX2, and Ki-67. In addition, Chi Squire goodness-of-fit test has been used to test equality of distribution between categories by sub groups at the baseline. Results: 59 women were enrolled and underwent an initial biopsy. The mean (range) age was 42 year (22-62) and the mean (range) weight and BMI prior to surgery was 127 kg (87-176) and 46.8 kg/m2 (36-64.3) respectively. Abnormal endometrial findings (three simple and one complex hyperplasia, all without atypia) were seen in 6.8% of patients presenting for bariatric surgery (4/59)). The sign-rank test demonstrated marginally significant difference (p-value=0.0522) in H score for ER. Statistically significant difference has been observed between matched pre and post surgery levels of CD20 based on exact McNemar test (p-value=0.0196). Since sample size was too small, McNemar-Bowker test didn't demonstrate significance for CD3, Cox2, and Ki-67. Nevertheless, the tendency towards decrease in the biomarker expression level has been observed for Ki67, and CD3. Conclusions: Morbidly obese women who present for bariatric surgery are at relatively high risk of harboring a premalignant condition of the endometrium. We are the first group to demonstrate that trends for improvement in several cancer associated markers can be achieved with weight loss, especially for CD20 and ER. Additional investigations of endometrial biomarker levels before and after bariatric surgery are needed in larger samples to evaluate if weight loss associated with bariatric surgery truly reduces the rate of uterine pathology. Citation Format: Faina Y. Linkov, Robert Edwards, Marina L. Komaroff, Esther Elishaev, Nika Gloyeske, Peter Argenta. Biomarker changes in the endometrium of morbidly obese women undergoing bariatric surgery: Implications for endometrial cancer risk reduction. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr LB-26. doi:10.1158/1538-7445.AM2013-LB-26

The Role of Preexisting Diabetes Mellitus on Incidence and Mortality of Endometrial Cancer

The results of cohort studies are controversial regarding the association between preexisting diabetes mellitus (DM) and the risk of endometrial cancer (EC) incidence and mortality. The aim of this meta-analysis was to assess whether an association exists between them in prospective studies. The PubMed and EMBASE database were searched for prospective cohort studies of preexisting DM on EC occurrence, mortality outcomes, updated up to June 2012. Data were independently extracted by 2 investigators using a standardized protocol. Summary relative risks (SRRs) with 95% confidence intervals (CIs) were estimated by the use of fixed-effect or random-effect models. Between-study heterogeneity was investigated using χ(2)-based Cochran Q statistic test and I statistics. A total of 21 cohort studies (20 articles) involving 12,195 incident cases and 575 deaths caused by EC were included in the analysis. Among these, 15 studies reported the risk of EC incidence, and 6 studies reported risk of EC mortality. The meta-analysis showed that DM was associated with an increased incidence of EC (SRR, 1.81; 95% CI, 1.38-2.37; test for heterogeneity: Q = 280.96, P < 0.001, I(2) = 95.4%), compared with individuals without diabetes or the general population. Subgroup analyses were conducted by geographical region, study design, year of publication, diabetes ascertainment, type of DM, and adjustments for some variables, and the positive association between DM and risk of EC was consistently observed in each subgroup. Sensitivity analyses also showed that no single study significantly influenced the pooled relative risk. No significant publication bias (P = 0.173) was found. Diabetes mellitus was not positively associated with EC mortality (SRR, 1.23; 95% CI, 0.80-1.90; test for heterogeneity: Q = 11.95, P = 0.035, I(2) = 58.2%). This meta-analysis of cohort studies suggests that there is a significant association between DM and increased risk of EC incidence but no increased risk of EC mortality.

Lifestyle-related biomarkers and endometrial cancer survival: Elevated gamma-glutamyltransferase as an important risk factor

Background: Lifestyle seems to play an important role in endometrial cancer mortality, but it remains unclear which biomarkers are involved. The aim of this study was to assess the extent of the association between lifestyle-related biomarkers and the survival of endometrial cancer patients. Methods: A sub-cohort of 242 endometrial cancer patients, from a population-based study of the more than 90,000 female participants of the Vorarlberg Health Monitoring and Promotion Programme, was followed for a median duration of twelve years. Besides age, tumour staging, and histology, also pre-diagnostic levels of body mass index, blood pressure, triglycerides, total cholesterol, glucose, gamma-glutamyltransferase (GGT), and serum uric acid were analysed in Cox proportional hazards regression models to estimate multivariate mortality risks. Results: During follow-up 89 deaths occurred of which 49 were cancer-related. Survival was associated with age, tumour stage, and histology. Of the biomarkers, log10-transformed GGT showed a large effect on cancer-related mortality (HR=3.35, 95% CI 1.12–10.03), whereas the other parameters did not appear with significant effects after adjustment for the other factors. Conclusion: Elevated level of GGT, a lifestyle-related marker, was associated with poor survival among endometrial cancer patients.

A contemporary analysis of clear cell carcinoma of the endometrium

Objectives: Clear cell carcinoma of the endometrium is a rare entity. Despite this, it contributes disproportionately to endometrial cancer mortality. Sufficient clinical information regarding treatment, behavior and prognosis is lacking. The aim of this study is to give a contemporary perspective, based on experience at two tertiary care cancer centers.

Endometrial cancer survival after breast cancer in relation to tamoxifen treatment: Pooled results from three countries

IntroductionTamoxifen is an effective treatment for breast cancer but an undesirable side-effect is an increased risk of endometrial cancer, particularly rare tumor types associated with poor prognosis. We investigated whether tamoxifen therapy increases mortality among breast cancer patients subsequently diagnosed with endometrial cancer.MethodsWe pooled case-patient data from the three largest case-control studies of tamoxifen in relation to endometrial cancer after breast cancer (1,875 patients: Netherlands, 765; United Kingdom, 786; United States, 324) and collected follow-up information on vital status. Breast cancers were diagnosed in 1972 to 2005 with endometrial cancers diagnosed in 1978 to 2006. We used Cox proportional hazards survival analysis to estimate hazard ratios (HRs) and 95% confidence intervals (CI).ResultsA total of 1,104 deaths occurred during, on average, 5.8 years following endometrial cancer (32% attributed to breast cancer, 25% to endometrial cancer). Mortality from endometrial cancer increased significantly with unfavorable non-endometrioid morphologies (P < 0.0001), International Federation of Gynaecology and Obstetrics staging system for gynecological malignancy (FIGO) stage (P < 0.0001) and age (P < 0.0001). No overall association was observed between tamoxifen treatment and endometrial cancer mortality (HR = 1.17 (95% CI: (0.89 to 1.55)). Tamoxifen use for at least five years was associated with increased endometrial cancer mortality (HR = 1.59 (1.13 to 2.25)). This association appeared to be due primarily to the excess of unfavorable histologies and advanced stage in women using tamoxifen for five or more years since the association with mortality was no longer significant after adjustment for morphological type and FIGO stage (HR = 1.37 (0.97 to 1.93)). Those patients with endometrioid tumors, who stopped tamoxifen use at least five years before their endometrial cancer diagnosis, had a greater mortality risk from endometrial cancer than endometrioid patients with no tamoxifen exposure (HR = 2.11 (1.13 to 3.94)). The explanation for this latter observation is not apparent.ConclusionsPatients with endometrial cancer after breast cancer who received tamoxifen treatment for five years for breast cancer have greater endometrial cancer mortality risk than those who did not receive tamoxifen. This can be attributed to non-endometrioid histological subtypes with poorer prognosis among long term tamoxifen users.

Prognostic Value of the 2009 FIGO Staging for Endometrial Cancer: An Illustration of the E3N Cohort

To compare the prognostic values of the 1988 and 2009 International Federation of Gynecology and Obstetrics (FIGO) classifications for endometrial cancer. From 1990 to 2008, patients undergoing surgery for endometrial cancer were extracted from the French prospective "Etude Epidémiologique auprès de femmes de l'Education Nationale" cohort study. Inclusion criteria were as follows: (1) an available detailed histologic report of primary surgical procedure and (2) available cause and date of death. Concordance indexes for the 1988 and 2009 FIGO classifications were compared. Three hundred ninety-seven patients fulfilled the inclusion criteria. The concordance index for the 2009 FIGO classification was lower than that of the 1988 FIGO classification (0.76 vs 0.77, respectively). In this study, the 1988 FIGO classification for endometrial cancer is at least as accurate as the 2009 FIGO classification for predicting endometrial cancer mortality.