Disease progression, survival, and molecular disparities in Black and White patients with endometrioid endometrial carcinoma in real-world registries and GOG/NRG oncology randomized phase III clinical trials.

OBJECTIVE: Investigate racial disparities in outcomes and molecular features in Black and White patients with endometrioid endometrial carcinoma (EEC). METHODS: Black and White patients diagnosed with EEC who underwent hysterectomy ± adjuvant treatment in SEER, National Cancer Database (NCDB), the Genomics Evidence Neoplasia Information Exchange (GENIE) project (v.13.0), and eight NCI-sponsored randomized phase III clinical trials (RCTs) were studied. Hazard ratio (HR) and 95% confidence interval (CI) were estimated for cancer-related death (CRD), non-cancer death (NCD), and all-cause death. RESULTS: Black (n = 4397) vs. White (n = 47,959) patients in SEER had a HR (95% CI) of 2.04 (1.87-2.23) for CRD and 1.22 (1.09-1.36) for NCD. In NCDB, the HR (95% CI) for death in Black (n = 13,468) vs. White (n = 155,706) patients was 1.52 (1.46-1.58) dropping to 1.29 (1.23-1.36) after propensity-score matching for age, comorbidity, income, insurance, grade, stage, LVSI, and treatment. In GENIE, Black (n = 109) vs. White (n = 1780) patients had fewer PTEN, PIK3R1, FBXW7, NF1, mTOR, CCND1, and PI3K-pathway-related gene mutations. In contrast, TP53 and DNA-repair-related gene mutation frequency as well as tumor mutational burden-high status were similar in Black and White patients. In RCTs, Black (n = 187) vs. White (n = 2877) patients were more likely to have advanced or recurrent disease, higher grade, worse performance status and progressive disease. Risk of death in Black vs. White patients in RCTs was 2.19 (1.77-2.71) persisting to 1.32 (1.09-1.61) after matching for grade, stage, and treatment arm while balancing age and performance status. CONCLUSIONS: Differences exist in clinical presentation, outcomes, and molecular features in Black vs. White patients with EEC in real-world registries and RCTs. Targeted-drug development, strategies to modify social determinants, and diverse inclusion in RCTs are approaches to reduce disparities.

Racial, ethnic and country of origin disparities in aggressive endometrial cancer histologic subtypes.

OBJECTIVE: This study investigated the risk of an aggressive endometrial cancer (EC) diagnosis by race, ethnicity, and country of origin to further elucidate histologic disparities in non-Hispanic Black (NHB), Hispanic, Asian/Pacific Islander (API), American Indian/Alaskan Native (AIAN) vs. non-Hispanic White (NHW) patients, particularly in Hispanic or API subgroups. METHODS: Patient diagnosed between 2004 and 2020 with low grade (LG)-endometrioid endometrial cancer (ECC) or an aggressive EC including grade 3 EEC, serous carcinoma, clear cell carcinoma, mixed epithelial carcinoma, or carcinosarcoma in the National Cancer Database were studied. The odds ratio (OR) and 95% confidence interval (CI) for diagnosis of an aggressive EC histology was estimated using logistic modeling. RESULTS: There were 343,868 NHW, 48,897 NHB, 30,013 Hispanic, 15,015 API and 1646 AIAN patients. The OR (95% CI) for an aggressive EC diagnosis was 3.07 (3.01-3.13) for NHB, 1.08 (1.06-1.11) for Hispanic, 1.17 (1.13-1.21) for API and 1.07 (0.96-1.19) for AIAN, relative to NHW patients. Subset analyses by country of origin illustrated the diversity in the OR for an aggressive EC diagnosis among Hispanic (1.18 for Mexican to 1.87 for Dominican), Asian (1.14 Asian Indian-Pakistani to 1.48 Korean) and Pacific Islander (1.00 for Hawaiian to 1.33 for Samoan) descendants. Hispanic, API and AIAN patients were diagnosed 5-years younger that NHW patients, and the risk for an aggressive EC histology were all significantly higher than NHW patients after correcting for age. Insurance status was another independent risk factor for aggressive histology. CONCLUSIONS: Risk of an aggressive EC diagnosis varied by race, ethnicity, and country of origin. NHB patients had the highest risk, followed by Dominican, South/Central American, Cuban, Korean, Thai, Vietnamese, and Filipino descendants.

The association of black race with receipt of hysterectomy and survival in low-risk endometrial cancer.

OBJECTIVE: To determine whether Black race is associated with treatment and survival among women with low-risk endometrial cancer. METHODS: Black and White women with Stage IA grade 1-2 endometrioid endometrial carcinoma diagnosed from 2010 to 2016 in the SEER 18 dataset were identified (n = 23,431), and clinical and socioeconomic attributes obtained. Five-year cancer-specific survival (CSS) and relative survival (RS) were calculated using SEER*Stat 8.3.9. Cox proportional hazards model was used to determine predictors of overall survival (OS) and CSS. RESULTS: There was a significantly higher proportion of Black women who did not have surgery compared to White women (3% vs 1%, respectively; p < 0.0001). Residing in the South, being insured with Medicaid, and residing in a county with low median income were also associated with non-receipt of surgery. Black women remained less likely to undergo hysterectomy on multivariable analysis (OR 0.44, 95% CI 0.32-0.60). Non-receipt of hysterectomy was predictive of decreased CSS (HR 0.14, 95% CI 0.09-0.21) and OS (HR 0.18, 95% 0.14-0.23) on adjusted analysis. Black race was also an independent predictor of increased cancer-specific death (HR 2.07, 95% CI 1.50-2.86) as well as death from any cause (HR 1.74, 95% CI 1.44-2.09) on adjusted analysis. CONCLUSIONS: Black women with low-risk endometrial cancer were less likely to undergo hysterectomy and experienced decreased survival relative to White women. Further investigation is warranted to better understand the socioeconomic, geographic, and biologic factors that influence this disparity.

Network Pharmacology-Based and Clinically Relevant Prediction of the Potential Targets of Chinese Herbs in Ovarian Cancer Patients.

Reports increasingly suggest that Chinese herbal medicine (CHM) has been used to treat ovarian cancer (OvCa) with a good curative effect; however, the molecular mechanisms underlying CHM are still unclear. In this retrospective study, we explored CHM's molecular targets for the treatment of OvCa based on clinical data and network pharmacology. We used the Kaplan-Meier method and Cox regression analysis to verify the survival rate of 202 patients with CHM-treated OvCa. The association between CHM and survival time was analyzed by bivariate correlation. A target network of CHM active ingredients against OvCa was established via network pharmacology. Cox regression analysis showed that CHM is an independent favorable prognostic factor. The median survival time was 91 months in the CHM group and 65 months in the non-CHM group. The survival time of FIGO stage III patients in the two groups was 91 months and 52 months, and the median survival period of FIOG stage IV patients was 60 months and 22 months, respectively (p < 0.001). Correlation analysis demonstrated that 12 herbs were closely associated with prognosis, especially in regard to the long-term benefits. Bioinformatics analysis indicated that the anti-OvCa activity of these 12 herbs occurs mainly through the regulation of apoptosis-related protein expression, which promotes OvCa cell apoptosis and inhibits OvCa development. They also regulate the progress of OvCa treatment by promoting or inhibiting protein expression on the p53 signaling pathway and by inhibiting the NF-κB signaling pathway by directly inhibiting NF-κB.

Black and Hispanic women are less likely than white women to receive guideline-concordant endometrial cancer treatment.

BACKGROUND: Differences in receipt of guideline-concordant treatment might underlie well-established racial disparities in endometrial cancer mortality. OBJECTIVE: Using the National Cancer Database, we assessed the hypothesis that among women with endometrioid endometrial cancer, racial/ethnic minority women would have lower odds of receiving guideline-concordant treatment than white women. In addition, we hypothesized that lack of guideline-concordant treatment was linked with worse survival. STUDY DESIGN: We defined receipt of guideline-concordant treatment using the National Comprehensive Cancer Network guidelines. Multivariable logistic regression models were used to compute odds ratios and 95% confidence intervals for associations between race and guideline-concordant treatment. We used multivariable Cox proportional hazards regression models to estimate hazards ratios and 95% confidence intervals for relationships between guideline-concordant treatment and overall survival in the overall study population and stratified by race/ethnicity. RESULTS: This analysis was restricted to the 89,319 women diagnosed with an invasive, endometrioid endometrial cancer between 2004 and 2014. Overall, 74.7% of the cohort received guideline-concordant treatment (n = 66,699). Analyses stratified by race showed that 75.3% of non-Hispanic white (n = 57,442), 70.1% of non-Hispanic black (n = 4334), 71.0% of Hispanic (n = 3263), and 72.5% of Asian/Pacific Islander patients (n = 1660) received treatment in concordance with guidelines. In multivariable-adjusted models, non-Hispanic black (odds ratio, 0.92, 95% confidence interval, 0.86-0.98) and Hispanic women (odds ratio, 0.90, 95% confidence internal, 0.83-0.97) had lower odds of receiving guideline-concordant treatment compared with non-Hispanic white women, while Asian/Pacific Islander women had a higher odds of receiving guideline-concordant treatment (odds ratio, 1.11, 95% confidence interval, 1.00-1.23). Lack of guideline-concordant treatment was associated with lower overall survival in the overall study population (hazard ratio, 1.12, 95% confidence interval, 1.08-1.15) but was not significantly associated with overall survival among non-Hispanic black (hazard ratio, 1.09, 95% confidence interval, 0.98-1.21), Hispanic (hazard ratio, 0.92, 95% confidence interval=0.78-1.09), or Asian/Pacific Islander (hazard ratio, 0.90, 95% confidence interval, 0.70-1.16) women. CONCLUSION: Non-Hispanic black and Hispanic women were less likely than non-Hispanic white women to receive guideline-concordant treatment, while Asian/Pacific Islander women more commonly received treatment in line with guidelines. Furthermore, in the overall study population, overall survival was worse among those not receiving guideline-concordant treatment, although low power may have had an impact on the race-stratified models. Future studies should evaluate reasons underlying disparate endometrial cancer treatment.

Chemotherapy, Radiation, or Combination Therapy for Stage III Uterine Cancer.

OBJECTIVE: To compare the outcomes of women with stage III uterine cancer treated with chemotherapy alone, external beam radiation alone, and combination chemotherapy and radiation. METHODS: The National Cancer Database was used to identify women with stage III endometrioid, serous, and clear cell uterine cancer treated with either chemotherapy (with or without vaginal brachytherapy) alone, external beam radiation (with or without brachytherapy), or combination chemotherapy and external beam radiation (with or without vaginal brachytherapy) from 2004 to 2015. Survival was estimated using Cox proportional hazards models and adjusted survival curves after propensity score analysis using inverse probability of treatment weighting to balance the clinical and demographic characteristics between the cohorts. RESULTS: Of the 20,873 patients identified, 9,456 (45.3%) received chemotherapy alone, 2,417 (11.6%) were treated with radiation alone, and 9,000 (43.1%) received chemotherapy in combination with external beam radiation. Use of combination therapy was 33.0% in 2004, and then rose to 50.5% in 2015. The mortality of the cohort was 33.1% and median survival was 115 months. Within the cohort, combination therapy was associated with a 23% reduction in mortality (hazard ratio [HR]=0.77; 95% CI 0.73-0.80) compared with chemotherapy alone. Similar findings of decreased mortality were noted in subgroup analyses for both stage IIIA (HR=0.81; 95% CI 0.68-0.98) and stage IIIC (HR=0.79; 95% CI 0.75-0.84) tumors. Similarly, when compared with radiation alone, combination therapy was accompanied by a 19% decrease in mortality (HR=0.81; 95% CI 0.73-0.89). Combination chemoradiation was associated with decreased mortality across all of the histologic subtypes. CONCLUSION: Among women with stage III uterine cancer, combination chemotherapy and external beam radiation is associated with decreased mortality compared with chemotherapy or radiation alone.

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

BACKGROUND: 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. OBJECTIVES: 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. STUDY DESIGN: 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. RESULTS: 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. CONCLUSION: 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.

Impact of hospital volume on racial disparities and outcomes for endometrial cancer.

OBJECTIVE: Little is known about the influence of hospital procedural volume on racial disparities for uterine cancer. We examined whether the magnitude of the survival differential between black and white women varied based on hospital procedural volume for endometrial cancer. METHODS: We utilized the National Cancer Data Base to examine women with endometrial cancer from 1998 to 2012. Annualized hospital procedural volume was calculated and hospitals grouped into volume-based quartiles. Multivariable models were developed to examine differences in two and five-year survival between black and white women across the hospital volume categories. Patients were classified as early or advanced stage and as type I (low grade, endometrioid) or type II (high grade endometrioid, other histologies) cancers. RESULTS: We identified 243,422 (75.0%) white and 27,764 (8.6%) black women treated at 1059 hospitals. Regardless of hospital volume, black women had decreased survival. For each tumor class, the absolute difference in adjusted two-year survival between black and white women decreased with increasing hospital volume. For example, for women with early-stage, type I tumors, the adjusted two-year survival differential between blacks and whites was -1.4% (95%CI, -2.4 to -0.5%) at low volume centers and decreased to -0.5% (95%CI, -0.9 to 0%) at high-volume hospitals (P<0.0001). For advanced stage, type I tumors, the adjusted survival differential decreased from -12.4% (95%CI, -24.0 to -0.9%) to 1.2% (95%CI, -2.9 to 5.3%) at high volume hospitals (P<0.0001). CONCLUSION: Black race is an independent predictor of mortality. The impact of race on mortality is mitigated, albeit not eliminated, by increasing hospital volume.

Endometrial carcinoma recurrence according to race and ethnicity: An NRG Oncology/Gynecologic Oncology Group 210 Study.

Non-Hispanic black (NHB) women are more likely to experience an endometrial carcinoma (EC) recurrence compared to non-Hispanic white (NHW) women. The extent to which tumor characteristics, socioeconomic status (SES) and treatment contribute to this observation is not well defined. In the NRG Oncology/Gynecology Oncology Group (GOG) 210 Study we evaluated associations between race/ethnicity and EC recurrence according to tumor characteristics with adjustment for potential confounders. Our analysis included 3,199 NHW, 532 NHB and 232 Hispanic women with EC. Recurrence was documented during follow-up. We used Cox regression to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for associations between race/ethnicity and EC recurrence in models stratified by histologic subtype (low-grade endometrioid, high-grade endometrioid, serous, mixed cell, carcinosarcoma, clear cell) or stage (I, II, III) and adjusted for age, SES, body mass index, smoking status and treatment. In histologic subtype-stratified models, higher EC recurrence was noted in NHB women with low-grade endometrioid (HR = 1.94, 95% CI = 1.21-3.10) or carcinosarcomas (HR = 1.66, 95% CI = 0.99-2.79) compared to NHWs. In stage-stratified models, higher EC recurrence was noted among NHB women with stage I (HR = 1.48, 95% CI = 1.06-2.05) and Hispanic women with stage III disease (HR = 1.81, 95% CI = 1.11-2.95). Our observations of higher EC recurrence risk among NHB and Hispanic women, as compared to NHW women, were not explained by tumor characteristics, SES, treatment or other confounders. Other factors, such as racial differences in tumor biology or other patient factors, should be explored as contributors to racial disparities in EC recurrence.

Type II Endometrial Cancer Overexpresses NILCO: A Preliminary Evaluation.

OBJECTIVE: The expression of NILCO molecules (Notch, IL-1, and leptin crosstalk outcome) and the association with obesity were investigated in types I and II endometrial cancer (EmCa). Additionally, the involvement of NILCO in leptin-induced invasiveness of EmCa cells was investigated. METHODS: The expression of NILCO mRNAs and proteins were analyzed in EmCa from African-American (n = 29) and Chinese patients (tissue array, n = 120 cases). The role of NILCO in leptin-induced invasion of Ishikawa and An3ca EmCa cells was investigated using Notch, IL-1, and leptin signaling inhibitors. RESULTS: NILCO molecules were expressed higher in type II EmCa, regardless of ethnic background or obesity status of patients. NILCO proteins were mainly localized in the cellular membrane and cytoplasm of type II EmCa. Additionally, EmCa from obese African-American patients showed higher levels of NILCO molecules than EmCa from lean patients. Notably, leptin-induced EmCa cell invasion was abrogated by NILCO inhibitors. CONCLUSION: Type II EmCa expressed higher NILCO molecules, which may suggest it is involved in the progression of the more aggressive EmCa phenotype. Obesity was associated with higher expression of NILCO molecules in EmCa. Leptin-induced cell invasion was dependent on NILCO. Hence, NILCO might be involved in tumor progression and could represent a new target/biomarker for type II EmCa.

Race-specific molecular alterations correlate with differential outcomes for black and white endometrioid endometrial cancer patients.

BACKGROUND: The objective of this study was to identify molecular alterations associated with disease outcomes for white and black patients with endometrioid endometrial cancer (EEC). METHODS: EEC samples from black (n = 17) and white patients (n = 13) were analyzed by proteomics (liquid chromatography-tandem mass spectrometry) and transcriptomics (RNA-seq). Coordinate alterations were validated with RNA-seq data from black (n = 49) and white patients (n = 216). Concordantly altered candidates were further tested for associations with race-specific progression-free survival (PFS) in black (n = 64) or white patients (n = 267) via univariate and multivariate Cox regression modeling and log-rank testing. RESULTS: Discovery analyses revealed significantly altered candidate proteins and transcripts between black and white patients, suggesting modulation of tumor cell viability in black patients and cell death signaling in black and white patients. Eighty-nine candidates were validated as altered between these patient cohorts, and a subset significantly correlated with differential PFS. White-specific PFS candidates included serpin family A member 4 (SERPINA4; hazard ratio [HR], 0.89; Wald P value = .02), integrin subunit α3 (ITGA3; HR, 0.76; P = .03), and Bet1 Golgi vesicular membrane trafficking protein like (BET1L; HR, 0.48; P = .04). Black-specific PFS candidates included family with sequence similarity 228 member B (FAM228B; HR, 0.13; P = .001) and HEAT repeat containing 6 (HEATR6; HR, 4.94; P = .047). Several candidates were also associated with overall survival (SERPINA4 and ITGA3) as well as PFS independent of disease stage, grade and myometrial invasion (SERPINA4, BET1L and FAM228B). CONCLUSIONS: This study has identified and validated molecular alterations in tumors from black and white EEC patients, including candidates significantly associated with altered disease outcomes within these patient cohorts. Cancer 2017;123:4004-12. © 2017 American Cancer Society.

The Hispanic Paradox in endometrial cancer: A National Cancer Database study.

OBJECTIVE: To compare the overall survival of non-Hispanic white and Hispanic women with endometrial cancer. METHODS: We performed an observational retrospective cohort study of Hispanic and non-Hispanic women with endometrial cancer from the 2004-2014 National Cancer Database. Baseline characteristics were compared with the Chi-squared test for categorical variables or the Mann-Whitney U test for ordinal or continuous variables. The Kaplan-Meier method was used to estimate unadjusted survival times, which were compared with the log-rank test. Missing data was imputed using multiple imputation with chained equations. A multivariable parametric accelerated failure time model for survival was used. Sensitivity analyses were performed using matched cohort analyses of the overall cohort, and of subgroups based on stage or type. RESULTS: 112,574 non-Hispanic and 6313 Hispanic women met inclusion criteria. Five-year survival was slightly higher for Hispanic women (83.1% (82.1-84.3%) versus 81.4% (81.2-81.7%), P=0.002). Hispanic women were younger, treated at lower volume hospitals, and more often diagnosed with a type II histology and stage II-IV disease compared to non-Hispanic women (all P<0.001). With multivariable adjustment for measured confounders, Hispanic women lived 8% longer than non-Hispanic women (time-ratio (95% CI) 1.08 (1.02-1.14), P=0.01). When bias-reducing matched cohort analyses were used for sensitivity analyses, Hispanic women did not have significantly different survival than non-Hispanic women. CONCLUSION: Hispanic ethnicity was not associated with a clinically meaningful difference in survival among women with endometrial cancer.

[Risk factors of endometriosis associated ovarian carcinoma in women aged 45 years and older].

Obiective: To explore the risk factors of endometriosis-associated ovarian cancer (EAOC) in women with ovarian endometriosis aged 45 years and older in China. Methods: The medical records of total 1 038 women aged 45 years and older with a surgicopathological diagnosis of ovarian endometriosis treated at Peking Union Medical College Hospital from December 1994 to December 2014 were reviewed. Histology evaluation determined ovarian endometriosis with (n=30) or without (n=1 008) ovarian cancer. Results: (1) There were 30 (2.9%, 30/1 018) cases confirmed as having EAOC. Clear cell carcinoma (63.3%, 17/30) and endometrioid adenocarcinoma (23.3%, 7/30) were commonly observed subtypes and 70.0% of EAOC patients were at stage Ⅰ. (2) Compared women with ovarian endometriosis in the same age group, patients with EAOC were older (50.8 vs 48.5 years, P=0.002). There were more in postmenopausal status at diagnosis of EAOC (P<0.01). There were more found with a mass ≥8 cm (P<0.01). Women with EAOC had higher prevalence of coexisting endometrial disorders (P=0.003). No differences were found in preoperative CA(125) value and infertile or nulliparous women (P>0.05). Conclusions: For women with ovarian endometriosis aged 45 years and older, the subgroup of patients characterized by postmenopausal status and ovarian endometrioma (≥8 cm) have a higher risk of EAOC. Active intervention or intensive follow-up should be considered for this population group, especially for those concurrent with endometrial disorders.

Surgical-pathological findings in type 1 and 2 endometrial cancer: An NRG Oncology/Gynecologic Oncology Group study on GOG-210 protocol.

OBJECTIVE: To report clinical and pathologic relationships with disease spread in endometrial cancer patients. METHODS: Surgical candidates with uterine cancer (adenocarcinoma or carcinosarcoma) who were eligible to participate in a surgical pathological study to create a clinically annotated tissue biorepository to support translational and clinical research studies. All patients were to undergo a hysterectomy, bilateral salpingo-oophorectomy, and bilateral pelvic and para-aortic lymphadenectomy. From 2003-2007, open eligibility enrollment was conducted, and from 2007-2011, eligibility was restricted to enrich underrepresented patients or those at high risk. RESULTS: This report details clinical pathological relationships associated with extra uterine disease spread of 5866 evaluable patients including those with endometrioid histology as well as papillary serous, clear cell and carcinosarcoma histologies. Review of unrestricted enrollment was constructed in an effort to capture a cross-section population representative of endometrial cancers seen by the GOG participating members. Evaluation of this group of patients suggested the more natural incidence of different surgical pathological findings as well as demographic information. The addition of 2151 patients enrolled during the restricted time interval allowed a total of 1630 poor histotype patients available for further analysis. As expected, endometrioid (E) cancers represented the largest enrollment and particularly E grade 1 and 2 (G1 and 2) were more frequently confined to the uterus. Grade 3 (G3) endometrioid cancers as well as the poor histotype (papillary serous, clear cell and carcinosarcoma) had a much greater propensity for extant disease. CONCLUSIONS: This study confirms the previously reported surgical pathological findings for endometrioid cancers but in addition, using a large database of papillary serous, clear cell and carcinosarcoma, surgical pathological findings substantiate the categorization of poor histotypes for these cancers.

Surgical wait time: A new health indicator in women with endometrial cancer.

OBJECTIVE: To evaluate factors associated with delayed surgical treatment among women with endometrial cancer. METHODS: Using the National Cancer Database (NCDB), we analyzed time to first surgery for epithelial endometrial cancer patients who underwent surgical treatment from 2003 to 2011. Poisson regression was used to examine delays >6weeks between diagnosis and surgery, controlled for patients' sociodemographic and clinical characteristics. Survival for women diagnosed between 2003 and 2006 with timely versus delayed surgery was compared using Cox proportional hazards regression. RESULTS: The study included 112,041 women diagnosed at 1108 continuously reporting NCDB hospitals. Survival through 2011 was available for 40,184 women. All patients underwent hysterectomy. Twenty-eight percent of patients underwent surgery >6weeks after diagnosis. Poisson regression estimates indicated that being younger than 40years old, being black or Hispanic, having Medicaid or being uninsured, or being from the lowest education quartile were associated with a significantly higher likelihood of surgical wait time>6weeks. Patients diagnosed in 2010-2011 were more likely (IRR 1.32, 95% CI 1.24-1.40) to undergo surgery >6weeks after diagnosis compared to patients treated in 2003. Survival for women with surgical wait times >6weeks was worse than those treated within 6weeks of diagnosis (HR 1.14, 95% CI 1.09-1.20). CONCLUSIONS: Being a minority patient and having lower socioeconomic status or poor insurance coverage were associated with an increased likelihood of delayed surgical treatment. Wait times >6weeks from diagnosis of endometrial cancer to definitive surgery may have a negative impact on survival.

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

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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. IMPACT: Increasing rates of aggressive endometrial cancers may widen the survival disparity between NHW and NHB women.

Overexpression of Lysine-Specific Demethylase 1 Is Associated With Tumor Progression and Unfavorable Prognosis in Chinese Patients With Endometrioid Endometrial Adenocarcinoma.

OBJECTIVE: Lysine-specific demethylase 1 (LSD1) is a kind of flavin adenine dinucleotide-dependent amine oxidase that regulates normal cellular differentiation, gene activation, tumorigenesis, and progression. This study aims to detect the expression level of LSD1 in endometrial cancer and to explore its role in the progression and prognosis of endometrioid endometrial adenocarcinoma (EEA). METHODS: Immunohistochemistry was used to examine the expression of LSD1 in 206 EEA specimens, 50 benign endometrial lesion specimens, and 45 normal endometrium specimens. χ Analysis, Kaplan-Meier method, and multivariate Cox proportional hazard analysis were applied for the statistical analysis. RESULTS: Compared with normal endometrium and benign endometrial lesion (both P < 0.001), LSD1 was overexpressed in EEA. LSD1 expression was correlated with histological grade, International Federation of Gynecology and Obstetrics (FIGO) stage, vascular/lymphatic invasion, depth of myometrial invasion, and lymph node metastasis. Results of the Kaplan-Meier analysis indicated that LSD1 expression was associated with overall survival (OS) and disease-free survival (DFS) of EEA. The negative expression LSD1 group had longer OS and DFS than did the positive expression group. The difference was significant (both P < 0.001, log-rank test). Multivariate Cox regression analysis revealed that the LSD1 expression status was an independent prognostic factor for both OS (P = 0.027) and DFS (P = 0.016) of patients with EEA. CONCLUSIONS: Overexpression of LSD1 may contribute to the progression of EEA and may thus serve as a new biomarker to predict the prognosis of EEA.

The influence of comorbid conditions on racial disparities in endometrial cancer survival.

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.

The complex triad of obesity, diabetes and race in Type I and II endometrial cancers: prevalence and prognostic significance.

BACKGROUND: We examined the distribution of obesity, diabetes, and race in Type I and Type II endometrial cancers (EC) and their associations with clinical outcomes. METHODS: A multi-institutional retrospective analysis of Type I and II EC cases from January 2005 to December 2010 was conducted. Type I (endometrioid), Type II (serous and clear cell), low grade (LG) (grade 1 and 2 endometrioid), and high grade (HG) (grade 3 endometrioid, serous, clear cell) cohorts were compared. Univariate and multivariate analyses were used to determine time-to-recurrence (TTR), recurrence-free survival (RFS), and overall survival (OS). RESULTS: Type I EC patients were more frequently obese than Type II (66% versus 51%, p<0.0001) and had similar rates of diabetes (25% versus 23%, p=0.69). African-Americans (AA) had higher median BMI than Caucasians in both Type I (p<0.001) and II (p<0.001) ECs, and were twice as likely to have diabetes (p<0.001). In Type I EC, DM was associated with worse RFS and OS in unadjusted and adjusted models (RFS HR 1.38, 95%CI 1.01-1.89; OS HR 1.86, 95%CI 1.30-2.67), but not with TTR. BMI was associated with improved TTR in the adjusted analysis for Type I EC (HR 0.98, 95%CI 0.95-1.0), but not with RFS or OS. There was no association between DM or BMI and outcomes in Type II or HG EC. AA race was not associated with RFS or OS on adjusted analyses in any group. CONCLUSIONS: Obesity and diabetes are highly prevalent in Type I and II ECs, especially in AA. DM was associated with worse RFS and OS in Type I EC. Neither DM nor BMI was associated with outcomes in Type II or HG EC.

Endometrial cancer in morbidly obese women: do racial disparities affect surgical or survival outcomes?

OBJECTIVE: Endometrial cancer mortality disproportionately affects black women and whether greater prevalence of obesity plays a role in this disparity is unknown. We examine the effect of race on post-surgical complications, length of stay, and mortality specifically in a morbidly obese population. METHODS: Black and white women with endometrial cancer diagnosed from 1996 to 2012 were identified from the University Pathology Group database in Detroit, Michigan, and records were retrospectively reviewed to obtain clinicopathological, demographic, and surgical information. Analysis was limited to those with a body mass index of 40kg/m(2) or greater. Differences in the distribution of variables by race were assessed by chi-squared tests and t-tests. Kaplan-Meier and Cox regression analyses were performed to examine factors associated with mortality. RESULTS: 97 white and 89 black morbidly obese women were included in this analysis. Black women were more likely to have type II tumors (33.7% versus 15.5% of white women, p-value=0.003). Hypertension was more prevalent in black women (76.4% versus 58.8%, p-value=0.009), and they had longer hospital stays after surgery despite similar rates of open vs minimally invasive procedures and lymph node dissection (mean days=5.4) compared to whites (mean days=3.5, p-value=0.036). Wound infection was the most common complication (16.5% in whites and 14.4% in blacks, p-value=0.888). Blacks were more likely to suffer other complications, but overall the proportions did not differ by race. In univariate analyses, black women had higher risk of endometrial cancer-related death (p-value=0.090). No racial differences were noted in adjusted survival analyses. CONCLUSION: A more complete investigation, incorporating socio-demographic factors, is warranted to understand the effects of morbid obesity and race on endometrial cancer.