Incidence Rates Of Endometrial Cancer Research Articles

Sociodemographic, clinical characteristics, and treatment patterns of endometrial cancer cases in Puerto Rico during the period 2009 to 2015: A retrospective study.

Over the past decades, the rising incidence rates of endometrial cancer have made it a significant public health concern for women worldwide. Treatment strategies for endometrial cancer vary based on several factors such as stage, histology, the patient's overall health, and preferences. However, limited amount of research on treatment patterns and potential correlations with sociodemographic characteristics among Hispanics is available. This study analyzes the treatment patterns for patients diagnosed with endometrial cancer in Puerto Rico. A secondary database analysis was performed on endometrial cancer cases reported to the Puerto Rico Central Cancer Registry-Health Insurance Linkage Database from 2009 to 2015 (n = 2,488). The study population's sociodemographic and clinical characteristics were described, along with an overview of the therapy options provided to patients receiving care on the island. Logistic regression models were used to evaluate the association of sociodemographic/clinical characteristics with treatment patterns stratified by risk of recurrence. In our cohort, most patients were insured through Medicaid and had a median age of 60 years. Almost 90% of patients received surgery as the first course of treatment. Surgery alone was the most common treatment for low-risk patients (80.2%). High-risk patients were more likely to receive surgery with radiotherapy and chemotherapy (24.4%). Patients with Medicare insurance were five times (HR: 4.84; 95% CI: 2.45-9.58; p < 0.001) more likely to receive surgery when compared with patients insured with Medicaid. In contrast, those with private insurance were twice as likely to receive surgery (HR: 2.38; 95% CI: 1.40-4.04; p = 0.001) when compared to those with Medicaid. These findings provide insight into the treatment patterns for endometrial cancer in Puerto Rico and highlight the importance of considering factors such as disease risk when making treatment decisions. Addressing these gaps in treatment patterns can contribute to effective management of endometrial cancer.

Hypertension and risk of endometrial cancer: a pooled analysis in the Epidemiology of Endometrial Cancer Consortium (E2C2).

The incidence rates of endometrial cancer (EC) are increasing, which may partly be explained by the rising prevalence of obesity, an established risk factor for EC. Hypertension, another component of metabolic syndrome, is also increasing in prevalence, and emerging evidence suggests that it may be associated with the development of certain cancers. The role of hypertension independent of other components of metabolic syndrome in the etiology of EC remains unclear. In this study we evaluated hypertension as an independent risk factor for EC and whether this association is modified by other established risk factors. We included 15,631 EC cases and 42,239 controls matched on age, race, and study-specific factors from 29 studies in the Epidemiology of Endometrial Cancer Consortium. We used multivariable unconditional logistic regression models to estimate odds ratios (ORs) and 95% confidence intervals (CIs) to evaluate the association between hypertension and EC and whether this association differed by study design, race/ethnicity, body mass index, diabetes status, smoking status, or reproductive factors. Hypertension was associated with an increased risk of EC (OR=1.14, 95% CI:1.09-1.19). There was significant heterogeneity by study design (Phet<0.01), with a stronger magnitude of association observed among case-control vs. cohort studies. Stronger associations were also noted for pre-/peri-menopausal women and never users of postmenopausal hormone therapy. Hypertension is associated with EC risk independently from known risk factors. Future research should focus on biologic mechanisms underlying this association. This study provides evidence that hypertension may be an independent risk factor for EC.

Incidence and mortality of endometrial cancer in China, data from China Cancer Registry Annual Report, 2004-2017

Objective: To analysis the incidence rate and mortality rate of endometrial cancer in China from 2004 to 2017 according to the data from China Cancer Registry Annual Report. Methods: The incidence and mortality data of endometrial cancer were extracted from the China Cancer Registry Annual Report 2004 to 2017, and the incidence, mortality, number of new cases, number of deaths were extracted according to the region (national, urban, rural and eastern, middle and western areas) and the age composition of population to estimate the incidence and mortality of endometrial cancer nationwide. The age-standardized incidence rate and mortality rate were calculated based on the Chinese standard population in 2000 (ASIRC, ASIRW) and Segi's world population (ASMRC, ASMRW). Join Point regression was used to calculate the annual percentage change of morbidity rate, and Cochran-Armitage trend test was used to analyze the changing trend of morbidity and mortality. Results: From 2004 to 2017, the number of women covered by the China Cancer Registry Annual Report has increased from 35 571 657 to 215 201 995, and the total population of the covered areas has increased from 5.53% to 31.39%. The crude incidence rate of endometrial cancer increased from 6.20/100 000 to 10.06/100 000, and showed an upward trend over time (P<0.001). After adjusting for age, ASIRC increased from 5.75/100 000 in 2004 to 6.79/100 000 in 2017, and ASIRW increased from 5.60/100 000 in 2004 to 6.56/100 000 in 2017, both showing an upward trend over time (all P<0.001). The crude incidence rates in urban area and rural area were respectively 10.89/100 000 and 9.25/100 000 in 2017, and the ASIRC was higher in urban than rural areas (7.14/100 000 vs 6.43/100 000) after adjusting for age. The ASIRW was higher in eastern areas than middle areas and western areas (7.16/100 000 vs 6.44/100 000 vs 5.60/100 000). The incidence rate in rural areas showed more significant growth than urban areas [annual percent change (APC): 3.2% vs 0.7%, P<0.001]. The age-specific incidence rate increased with age and reached a peak in the age group of 50-54 years (25.70/100 000). Incidence rate in the under-40 age group increased more in rural areas than in urban areas (69.84% vs-7.09%). From 2004 to 2017, the age-standardized mortality rate shows a decreasing trend, with the ASMRC from 1.83/100 000 to 1.47/100 000, and the ASMRW from 1.81/100, 000 to 1.46/100, 000. There was no significant difference between urban and rural areas in mortality of endometrial cancer. Age-specific mortality rates increased with age, reaching a peak in the age group 85 years and older (13.16/100 000). Conclusions: Recent years, there was an increasing incidence rate of endometrial cancer in China. Especially in rural areas, the incidence rate of endometrial cancer is increasing rapidly in young women under 40 years of age. There were differences between urban and rural areas and regions in the incidence rate of endometrial cancer. The incidence rates of endometrial cancer in some high-income cities have occupied the first place of female reproductive system malignant cancers. The age-standardized mortality rate of endometrial cancer shows a decreasing trend.

A comparative analysis of endometrial cancer disparities in incidence, mortality, and survival between women living in Puerto Rico, Non-Hispanic Blacks, Non-Hispanic Whites, and US Hispanics between 2000–2018

ObjectiveEndometrial cancer diagnosis in younger women is increasing in Puerto Rico and the United States. The study aims to evaluate the endometrial cancer trends in incidence, mortality, and survival by comparing US ethnic groups (NHW, NHB, and Hispanic) to women living in PR to assess whether disparities exist by age and stage at diagnosis on outcomes of interest. MethodsWe performed a secondary data analysis and comparison of the age-specific and age-adjusted incidence rates, mortality rates, and the survival of endometrial cancer in PR with that of NHB, NHW, and Hispanic using data from the PR Central Cancer Registry, the SEER Program, and PR Demographic Registry from 2000 to 2018. ResultsPR had the highest incidence rates (41.3 per 100,000 women) of endometrial cancer, followed by NHW, NHB, and Hispanic. Women in PR younger than 65 years old had higher incidence rates of endometrial cancer than compared groups. NHB have higher overall mortality rates (12.5 per 100,000 women). Between ages 20–34 and 35–49, women in PR have the highest mortality rates, and after age 50, mortality rates are higher for NHB. ConclusionsWomen in PR had higher endometrial cancer incidence rates in increasing trend from 2000 to 2018 compared to similar NHB, Hispanic, and NHW cohorts. Also, women in PR experienced higher incidence and mortality rates below 50 years old among all races and ethnicities. Future studies are needed to evaluate histology, obesity trends, and the impact on the quality of life for this cohort.

Association between consumption of sweeteners and endometrial cancer risk: a systematic review and meta-analysis of observational studies.

The purpose of this study is to further investigate the relationship between sweetener exposure and the risk of endometrial cancer (EC). Up until December 2022, a literature search in an electronic database was carried out utilizing PubMed, Web of Science, Ovid, and Scopus. The odds ratio (OR) and 95 % confidence interval (CI) were used to evaluate the results. Sweeteners were divided into nutritional sweeteners (generally refers to sugar, such as sucrose and glucose) and non-nutritional sweeteners (generally refers to artificial sweeteners, such saccharin and aspartame). Ten cohort studies and two case-control studies were eventually included. The study found that in 12 studies, compared with the non-exposed group, the incidence rate of EC in the sweetener exposed group was higher (OR = 1·15, 95 % CI = [1·07, 1·24]). Subgroup analysis showed that in 11 studies, the incidence rate of EC in the nutritional sweetener exposed group was higher than that in the non-exposed group (OR = 1·25, 95 % CI = [1·14, 1·38]). In 4 studies, there was no difference in the incidence rate of EC between individuals exposed to non-nutritional sweeteners and those who were not exposed to non-nutritional sweeteners (OR = 0·90, 95 % CI = [0·81, 1·01]). This study reported that the consumption of nutritional sweeteners may increase the risk of EC, whereas there was no significant relationship between the exposure of non-nutritional sweeteners and the incidence of EC. Based on the results of this study, it is recommended to reduce the intake of nutritional sweeteners, but it is uncertain whether use of on-nutritional sweeteners instead of nutritional sweetener.

Risk prediction models for endometrial cancer: development and validation in an international consortium.

Endometrial cancer risk stratification may help target interventions, screening, or prophylactic hysterectomy to mitigate the rising burden of this cancer. However, existing prediction models have been developed in select cohorts and have not considered genetic factors. We developed endometrial cancer risk prediction models using data on postmenopausal White women aged 45-85 years from 19 case-control studies in the Epidemiology of Endometrial Cancer Consortium (E2C2). Relative risk estimates for predictors were combined with age-specific endometrial cancer incidence rates and estimates for the underlying risk factor distribution. We externally validated the models in 3 cohorts: Nurses' Health Study (NHS), NHS II, and the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial. Area under the receiver operating characteristic curves for the epidemiologic model ranged from 0.64 (95% confidence interval [CI] = 0.62 to 0.67) to 0.69 (95% CI = 0.66 to 0.72). Improvements in discrimination from the addition of genetic factors were modest (no change in area under the receiver operating characteristic curves in NHS; PLCO = 0.64 to 0.66). The epidemiologic model was well calibrated in NHS II (overall expected-to-observed ratio [E/O] = 1.09, 95% CI = 0.98 to 1.22) and PLCO (overall E/O = 1.04, 95% CI = 0.95 to 1.13) but poorly calibrated in NHS (overall E/O = 0.55, 95% CI = 0.51 to 0.59). Using data from the largest, most heterogeneous study population to date (to our knowledge), prediction models based on epidemiologic factors alone successfully identified women at high risk of endometrial cancer. Genetic factors offered limited improvements in discrimination. Further work is needed to refine this tool for clinical or public health practice and expand these models to multiethnic populations.

Abstract PD12-07: Incidences of endometrial events and frequencies of endometrial invasive diagnostic procedures in breast cancer survivors on tamoxifen: A nationwide study

Abstract BackgroundBreast cancer survivors who taking tamoxifen as adjuvant therapy have been reported to have more endometrial lesions. According to guidelines, a gynecological assessment is recommended for postmenopausal women, but there is no mention of premenopausal women. The purpose of this study is to compare the risk of endometrial cancer by age at diagnosis, and to investigate frequencies of gynecological exam in breast cancer patients taking tamoxifen in South Korea. MethodsA nationwide retrospective cohort study was conducted using South Korea Health Insurance Review and Assessment Service claims data. Between 2010 and 2015, a total of 60,545 (mean follow-up, 66.0 months) newly diagnosed female breast cancer survivors were included. Endometrial evaluation and Dilatation &amp; Curettage (D&amp;C) proportion were analyzed by age at diagnosis. The incidence of endometrial cancer and benign lesions were calculated as incident cases per person-year and analyzed with the Kaplan-Meier method. ResultsThe 26,374 patients who taking tamoxifen were divided into four groups by age at diagnosis. The incidence rate of endometrial cancer per 1,000 person-years was 1.13 and 1.45 for age range 50-59 and over 60 and 0.62 and 0.82 for in age under 40 and range 40-49. However, D&amp;C proportion did not all differ from 10 to 11% in each subgroup. ConclusionsThis nationwide cohort study showed that the risk of endometrial cancer in premenopausal breast cancer women taking tamoxifen was lower than that of postmenopausal women. However, the invasive diagnostic procedure such as aspiration, biopsy, polypectomy and D&amp;C was proceeding at a level that makes no difference with those in postmenopausal women. Citation Format: Soojeong Choi, Jae ho Jeong, Jinhong Jung, Young Jae Lee, Jong Won Lee, Beom Seok Ko, Byung Ho Son, Sei Hyun Ahn, Yura Lee, Hee jeong Kim, Il Yong Chung. Incidences of endometrial events and frequencies of endometrial invasive diagnostic procedures in breast cancer survivors on tamoxifen: A nationwide study [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PD12-07.

Fertility-sparing treatment in early endometrial cancer: current state and future strategies.

Endometrial cancer (EC) is the fifth most common cancer in women worldwide. Global estimates show rising incidence rates in both developed and developing countries. Most women are diagnosed postmenopausal, but 14–25% of patients are premenopausal and 5% are under 40 years of age. Established risk factors include age and hyperestrogenic status associated with nulliparity, obesity, and metabolic syndrome. Standard treatment for EC, which involves total hysterectomy and bilateral salpingo-oophorectomy, has excellent survival outcomes, particularly for low-grade endometrioid tumors. However, it leads to permanent loss of fertility among women who wish to preserve their reproductive potential. With current trends of reproductive-age women delaying childbearing, rising EC incidence rates, and a growing epidemic of obesity, particularly in developed countries, research on conservative non-surgical treatment approaches remains a top priority. Fertility-sparing treatment predominantly involves the use of oral progestins and levonorgestrel-releasing intrauterine devices, which have been shown to be feasible and safe in women with early stage EC and minimal or no myometrial invasion. However, data on the efficacy and safety of conservative management strategies are primarily based on retrospective studies. Randomized clinical trials in younger women and high-risk obese patients are currently underway. Here, we have presented a comprehensive review of the current literature on conservative, fertility-sparing approaches, defining the optimal candidates and evaluating tumor characteristics, reproductive and oncologic outcomes, and ongoing clinical trials. We have also summarized current guidelines and recommendations based on the published literature.

Expression of L1CAM and KI-67 in Endometrial Cancer of Egyptian Females: Clinical Impact and Survival

Introduction: Endometrial adenocarcinoma is characterized by a good prognosis. However, the disease response shows a significant heterogeneity. Treatment of endometrial cancer (EC) is still based on clinico-pathological parameters, which have limited role in risk stratification. There is a need for more determinant markers, such as L1 Cell Adhesion Molecule (L1CAM), to identify patients at higher risk of relapse and tailor a more convenient treatment. L1CAM has a capacity to enhance cell motility and promote tumor invasion in different malignancies. In Egypt, the incidence rate of EC is growing over time. Especially in Elgharbiah governorate (home of this study). L1CAM expression and Ki-67 was reported and compared with other clinico-pathological criteria. Method: Seventy-six female patients of endometrial carcinomas were involved in this prospective study. The patients were treated and followed up at Tanta University Hospitals in the period between January 2015 to April 2019. L1CAM expression and Ki-67 was detected by immuno-histochemical exam and compared with other clinico-pathological criteria. Survival was assessed and compared by Kaplan-Meier curves and log-rank test. Results: Positive L1CAM expression was detected in 17 patients (22.4%) and was significantly correlated with unfavorable prognostic factors such as higher stage and grade ( P= 0.021 and P =0.001 respectively), lympo-vascular invasion ( P &lt;0.001), non-endometroid type ( P &lt;0.027) and Ki-67 ( P= 0.003). Univariate analysis revealed that: positive L1CAM; higher tumor grade; high stage; and non-endometrioid type were significantly associated with shorter disease-free survival (DFS) but no significant correlation was detected between Ki-67 and DFS. In multivariate analysis, positive L1CAM remained statistically significant with DFS [P =0.045; 95%CI (1.028:11.17); HR=3.38]. Conclusion: Our study indicates that L1CAM expression and Ki-67 are significantly associated with poor tumor characteristics. L1CAM is significantly associated with shorter disease-free survival and may be a helpful tool as a part of a simple clinical molecular classification for EC.

Theoretical potential for endometrial cancer prevention through primary risk factor modification: Estimates from the EPIC cohort.

Endometrial cancer (EC) incidence rates vary ~10‐fold worldwide, in part due to variation in EC risk factor profiles. Using an EC risk model previously developed in the European EPIC cohort, we evaluated the prevention potential of modified EC risk factor patterns and whether differences in EC incidence between a European population and low‐risk countries can be explained by differences in these patterns. Predicted EC incidence rates were estimated over 10 years of follow‐up for the cohort before and after modifying risk factor profiles. Risk factors considered were: body mass index (BMI, kg/m2), use of postmenopausal hormone therapy (HT) and oral contraceptives (OC) (potentially modifiable); and, parity, ages at first birth, menarche and menopause (environmentally conditioned, but not readily modifiable). Modeled alterations in BMI (to all ≤23 kg/m2) and HT use (to all non‐HT users) profiles resulted in a 30% reduction in predicted EC incidence rates; individually, longer duration of OC use (to all ≥10 years) resulted in a 42.5% reduction. Modeled changes in not readily modifiable exposures (i.e., those not contributing to prevention potential) resulted in ≤24.6% reduction in predicted EC incidence. Women in the lowest decile of a risk score based on the evaluated exposures had risk similar to a low risk countries; however, this was driven by relatively long use of OCs (median = 23 years). Our findings support avoidance of overweight BMI and of HT use as prevention strategies for EC in a European population; OC use must be considered in the context of benefits and risks.

Palbociclib Promotes Dephosphorylation of NPM/B23 at Threonine 199 and Inhibits Endometrial Cancer Cell Growth.

Endometrial cancer incidence rates are growing, especially in countries with rapid socioeconomic transitions. Despite recent advances in chemotherapy, hormone therapy, and targeted therapy, advanced/recurrent disease remains a clinical challenge. Palbociclib—a selective inhibitor of cyclin-dependent kinases (CDK) 4/6—has therapeutic potential against estrogen receptor (ER)-positive and HER2-negative breast cancer. However, the question as to whether it can be clinically useful in endometrial cancer remains open. Here, we show that combined treatment with palbociclib and megesterol acetate exerts synergistic antiproliferative effects against endometrial cancer cells. Treatment of cancer cells with palbociclib suppressed NPM/B23 phosphorylation at threonine 199 (Thr199). We further demonstrated that CDK6 acts as a NPM/B23 kinase. Palbociclib-induced NPM/B23 dephosphorylation sensitized endometrial cancer cells to megesterol acetate through the upregulation of ERα expression. Immunohistochemistry revealed an overexpression of phospho-NPM/B23 (Thr199) in human endometrial cancer, and phospho-NPM/B23 (Thr199) expression levels were inversely associated with Erα in clinical specimen. In a xenograft tumor model, the combination of palbociclib and megesterol acetate successfully inhibited tumor growth. Taken together, our data indicate that palbociclib promoted NPM/B23 dephosphorylation at Thr199—an effect mediated by disruption of CDK6 kinase activity. We conclude that palbociclib holds promise for the treatment of endometrial cancer when used in combination with megesterol acetate.

Assessing endometrial cancer risk among US women: long-term trends using hysterectomy-adjusted analysis

Commonly reported incidence rates for endometrial cancer fail to take into account both the large number of hysterectomies performed each year and the dynamic change in hysterectomy rate over the past decade. Large racial differences in premenopausal hysterectomy rates between Black and White women in the United States likely affect calculation of race-based risk. The objectives of the study were to determine how the long-term trends in Black-White differences in endometrial cancer incidence and histology type have changed over time for women at risk. Using longitudinal Surveillance, Epidemiology, and End Results data from 1997 to 2014 and state-level hysterectomy prevalence from the Behavioral Risk Factor Surveillance System, we calculated hysterectomy-adjusted incidence rates of endometrial cancer and the proportion of high vs low-risk endometrial cancer, by race, over time. In women older than 50 years who have not had a hysterectomy, endometrial cancer incidence is 87 per 100,000 from 1997 to 2014. Among White women endometrial cancer incidence changed from 102 (1997-2001) to 86 (2012-2014) cases per 100,000, with a nonsignificant decreasing linear trend (adjusted risk ratio, 0.95; 95% confidence interval, 0.91-1.00; p=0.05). In contrast, incidence for Black women was 88 (1997-2001), 101 (2002-2006), 100 (2007-2011), and 102 (2012-2014) cases per 100,000 with no decreasing trend (adjusted risk ratio, 1.02; 95% confidence interval, 0.96-1.10, P= .449). High-risk histology increased among both groups (White: adjusted risk ratio, 1.06; 95% confidence interval, 1.01-1.11; P= .015; Black: adjusted risk ratio, 1.06; 95% confidence interval, 1.02-1.10, P= .007). Racial difference in the proportion of high-risk disease remained stable. Updated hysterectomy-adjusted incidence demonstrates that endometrial cancer is the second most common cancer among women older than 50 years with a uterus and that endometrial cancer has been more common among Black women compared with White women in the United States since 2002. A clinical approach of proactive communication and routine screening for early symptoms in the perimenopausal and menopausal years, especially among Black women, is warranted. These findings can also inform equitable distribution of research funding for endometrial cancer and serve to promote public awareness of this common cancer.

3296 Endometrial cancer microbiome biomarker for disease detection and microbial role in the disease

OBJECTIVES/SPECIFIC AIMS: Our primary objective is to determine whether the bacteria exerts its effect intra- or extra-cellularly. We have genomic and microscopy preliminary evidence indicating that the bacteria is capable of invading endometrial cells. Our secondary objective is to identify what type of impact the bacteria have on the host cells and whether they are capable of transforming the host cells from a benign into a malignant phenotype. We are currently testing a putative mechanism by which the bacteria may cause the overexpression of the hypoxia inducible factor (HIF), a hallmark of endometrial cancer. METHODS/STUDY POPULATION: We are utilizing our custom built optofluidics platform (microfluidics platform incorporated into an advanced microscope with optical laser tweezers) to isolate single cells from the endometrial tissues of 150 patients with and without endometrial cancer. We are utilizing single cell whole genome amplification followed by qPCR to identify if the bacteria is present intracellularly. We are coupling this procedure with standard microbiological invasion assays with endometrial cell line cultures and P.somerae. We are also utilizing our optofluidics platform to perform single cell transcriptomic amplification, followed by sequencing of cells invaded or in the presence of the bacteria to determine the impact in the transcriptome of the host cell. We are coupling this with western blots of factors hypothesized to be impacted by the bacteria in the overexpression of HIF. RESULTS/ANTICIPATED RESULTS: Based on our preliminary data we anticipate to find evidence that P.somerae is invading the host cells, in particular the cells in tumor tissues. We also expect to find that the intracellular presence of the bacteria is causing the overexpression of the HIF pathway, hence resulting in a cancerous phenotype. DISCUSSION/SIGNIFICANCE OF IMPACT: Our long-term goal is to develop primary prevention strategies that will reduce endometrial cancer incidence rates. A confirmation of our hypothesis could suggest that it is sufficient for endometrial cancer prevention efforts to eliminate P.somerae, in line with gastric and cervical cancer efforts. It could also mean that targeting P.somerae in cancer treatment is necessary to contain the disease and prevent recurrence.

Abstract 843: Assessment of high-dose radiation efficacy administered to patient-derived xenografts based on the genomic reclassification of endometrial carcinomas

Abstract Adjuvant treatment of patients with endometrial cancer (EC) is tailored to clinical-pathologic prognostic factors. Pelvic radiation therapy for stage I EC provides a highly significant improvement of local control, but without survival advantage, and the use of adjuvant radiotherapy (RT) is limited to patients with high-intermediate or high-risk factors. Due to a rising incidence rate of EC there is an immediate need to improve how adjuvant treatments are being selected. The exploration of four genomic clusters by The Cancer Genome Atlas (TCGA) Network provides molecular insights and opportunity to refine current management strategies. However, no prospective validation of the relationship between cluster-association and treatment response has been reported. In this study, we evaluated the therapeutic efficacy of high-dose rate (HDR) radiation on the basis of genomic clusters. Objectives: To evaluate treatment response of HDR radiation according to TCGA classification using a panel of endometrial cancer patient-derived xenografts (EC-PDXs). Methods: Thirty-two EC-PDXs upon histologic and genomic characterization were orthotopically transplanted and propagated. Subcutaneously grafted PDX were subjected to a PDX clinical radiation trial. Animals were placed under a lead shield for irradiation once tumors reached 150-200 mm3 and 7Gy of radiation was delivered weekly for three weeks. Two additional weeks were given to investigate potential tumor regrowth. Histologic evaluation was conducted upon necropsy. Results: The overall response rate was 78% (25/32), in which high-grade ECs exhibited increased sensitivity to radiation compared to low-grade ECs (overall response rate 89% for high-grade versus 62% for low-grade). Copy number high (CNH) EC-PDXs showed the best response rate (100%), microsatellite instable (MSI) lines responded moderately (73%), and copy number low (CNL) lines exhibited the lowest response rate (42.9%). Nonresponders were noted among CNL and MSI clusters featuring low-grade endometrioid histology. Further evaluation of the proliferation index confirmed that all responders had a &amp;gt;90% decrease on H-score compared to the nonresponders, which either showed a slight decrease or no changes at all. Conclusions: This is the first radiation treatment study selecting candidates within a PDX clinical trial based on TCGA cluster affiliation. Our findings suggest that EC-PDXs categorized as CNH or with higher histologic grade seem more sensitive to radiotherapy. Therefore, special attention and reconsideration of treatment recommendation should be given to patients harboring tumors with MSI and CNL genomic features. Further studies towards the identification of biomarkers or additional subclusters within responders and nonresponders will benefit physicians and patients to direct therapy. Citation Format: Chieh-Hsiang Yang, David K. Gaffney, Elke A. Jarboe, Margit M. Janát-Amsbury. Assessment of high-dose radiation efficacy administered to patient-derived xenografts based on the genomic reclassification of endometrial carcinomas [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 843.

Hysterectomy-corrected rates of endometrial cancer among women younger than age 50 in the United States.

This analysis describes the impact of hysterectomy on incidence rates and trends in endometrioid endometrial cancer in the United States among women of reproductive age. Hysterectomy prevalence for states containing Surveillance, Epidemiology, and End Results (SEER) registry was estimated using data from the Behavioral Risk Factor Surveillance System (BRFSS) between 1992 and 2010. The population was adjusted for age, race, and calendar year strata. Age-adjusted incidence rates and trends of endometrial cancer among women age 20-49 corrected for hysterectomy were estimated. Hysterectomy prevalence varied by age, race, and ethnicity. Increasing incidence trends were observed, and were attenuated after correcting for hysterectomy. Among all women, the incidence was increasing 1.6% annually (95% CI 0.9, 2.3) and this increase was no longer significant after correction for hysterectomy (+ 0.7; 95% CI - 0.1, 1.5). Stage at diagnosis was similar with and without correction for hysterectomy. The largest increase in incidence over time was among Hispanic women; even after correction for hysterectomy, incidence was increasing (1.8%; 95% CI 0.2, 3.4) annually. Overall, endometrioid endometrial cancer incidence rates in the US remain stable among women of reproductive age. Routine reporting of endometrial cancer incidence does not accurately measure incidence among racial and ethnic minorities.

Association between tubal ligation and endometrial cancer risk: A Swedish population-based cohort study.

Tubal ligation results in less advanced stages and lower risk of metastatic spread at diagnosis of endometrial cancer (EC) but the primary preventive effect of the procedure is unclear. In a Swedish nationwide population-based cohort study, we crosslinked registry data for tubal ligation, EC, and death for Swedish women between 1973 and 2010. All women were followed until EC, emigration, hysterectomy for non-cancerous reasons, death, or end of follow-up. Primary outcome was incidence of EC and secondary outcome overall survival. We calculated adjusted incidence rates (IR) per 100,000 person-years and hazard ratios (HR) using Cox regression models. A total of 35,711 cases of EC were identified among 5,385,186 women. The IR of EC among exposed was 17.7 (95% CI 15.7-19.9) versus 29.0 (95% CI 28.7-29.3) among unexposed (per 100,000 women years). Exposed individuals had significantly reduced risk of EC (HR 0.73, 95% CI 0.65-0.83). The mortality rate among women with EC was 72% lower in exposed compared to unexposed (IR 1,441; 95% CI 1,089-1,907 and IR 5,136; 95% CI 5,065-5,209, respectively) which following adjustment corresponded to a HR of 0.71 (95% CI 0.49-1.03). Tubal ligation was associated with lower risk of EC as well as mortality rates in women with EC. Elective tubal ligation may be adopted in future cancer preventive strategies but must be balanced against the irreversibility of the procedure, which preclude further unassisted reproduction.

The incidence rates of endometrial hyperplasia and endometrial cancer: a four-year population-based study.

IntroductionThe aim of this study was to determine the incidence rates of endometrial hyperplasia (EH) and endometrial cancer (EC) in the Republic of Korea using national insurance claim data generated from 2009 to 2012.Materials and MethodsData that were generated from 2009 to 2012 were sourced from the Korean Health Insurance Review and Assessment Service-National Inpatients Sample database. The data from women who were assigned diagnosis codes representing EH or EC within 1 month of being assigned codes that corresponded to procedures that included endometrial biopsies and several types of gynecologic surgeries to obtain endometrial pathology samples, were selected for analysis.ResultsData from 2,477,424 women were entered into the database between 2009 and 2012, and the data from 1,868 women with EH and 868 women with EC were extracted for analysis. The mean ages of the patients were 44.1 ± 0.4 years for those with EH and 52.7 ± 0.6 years for those with EC. The EH and EC incidence rates were 37 per 100,000 woman-years and 8 per 100,000 woman-years, respectively. The EH and EC incidence rates peaked when the women were in their late forties and fifties, respectively.ConclusionsThe EH and EC incidence rates determined in this study were somewhat lower than those determined from previous studies. Further studies are required that adjust the data for race, menopausal hormone therapy, and obesity.

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.

Cancer of the corpus uteri.

Cancer of the corpus uteri.

Endometrial cancer and oral contraceptives: an individual participant meta-analysis of 27 276 women with endometrial cancer from 36 epidemiological studies

Oral contraceptives are known to reduce the incidence rate of endometrial cancer, but it is uncertain how long this effect lasts after use ceases, or whether it is modified by other factors. Individual participant datasets were sought from principal investigators and provided centrally for 27 276 women with endometrial cancer (cases) and 115 743 without endometrial cancer (controls) from 36 epidemiological studies. The relative risks (RRs) of endometrial cancer associated with oral contraceptive use were estimated using logistic regression, stratified by study, age, parity, body-mass index, smoking, and use of menopausal hormone therapy. The median age of cases was 63 years (IQR 57-68) and the median year of cancer diagnosis was 2001 (IQR 1994-2005). 9459 (35%) of 27 276 cases and 45 625 (39%) of 115 743 controls had ever used oral contraceptives, for median durations of 3·0 years (IQR 1-7) and 4·4 years (IQR 2-9), respectively. The longer that women had used oral contraceptives, the greater the reduction in risk of endometrial cancer; every 5 years of use was associated with a risk ratio of 0·76 (95% CI 0·73-0·78; p<0·0001). This reduction in risk persisted for more than 30 years after oral contraceptive use had ceased, with no apparent decrease between the RRs for use during the 1960s, 1970s, and 1980s, despite higher oestrogen doses in pills used in the early years. However, the reduction in risk associated with ever having used oral contraceptives differed by tumour type, being stronger for carcinomas (RR 0·69, 95% CI 0·66-0·71) than sarcomas (0·83, 0·67-1·04; case-case comparison: p=0·02). In high-income countries, 10 years use of oral contraceptives was estimated to reduce the absolute risk of endometrial cancer arising before age 75 years from 2·3 to 1·3 per 100 women. Use of oral contraceptives confers long-term protection against endometrial cancer. These results suggest that, in developed countries, about 400 000 cases of endometrial cancer before the age of 75 years have been prevented over the past 50 years (1965-2014) by oral contraceptives, including 200 000 in the past decade (2005-14). Medical Research Council, Cancer Research UK.