Endometrioid Endometrial Cancer Research Articles

Ascorbate exhibits anti-tumorigenic effects in pre-clinical models of endometrioid endometrial cancer (043)

Ascorbate exhibits anti-tumorigenic effects in pre-clinical models of endometrioid endometrial cancer (043)

Disparities in oncofertility referral, treatment utilization, and fertility outcomes among women with atypical hyperplasia or early endometrioid endometrial cancer treated with the levonorgestrel intrauterine device (2228)

Disparities in oncofertility referral, treatment utilization, and fertility outcomes among women with atypical hyperplasia or early endometrioid endometrial cancer treated with the levonorgestrel intrauterine device (2228)

The oncologic and pregnancy outcomes of fertility-sparing hormonal treatment in patients with early endometrioid endometrial cancer of all grade: A Korean multicenter retrospective study of the GORILLA group (GORILLA-2001) (1294)

The oncologic and pregnancy outcomes of fertility-sparing hormonal treatment in patients with early endometrioid endometrial cancer of all grade: A Korean multicenter retrospective study of the GORILLA group (GORILLA-2001) (1294)

Tumor location as a risk factor for lymph node metastasis in presumed early-stage endometrioid endometrial cancer patients (1225)

Tumor location as a risk factor for lymph node metastasis in presumed early-stage endometrioid endometrial cancer patients (1225)

Multiple differences in signaling pathways and single gene expression patterns exist in high grade endometrioid endometrial cancer in Black and White patients after accounting for BMI: A single-site pilot study (2258)

Multiple differences in signaling pathways and single gene expression patterns exist in high grade endometrioid endometrial cancer in Black and White patients after accounting for BMI: A single-site pilot study (2258)

Clinical and mutational profile of AT-rich interaction domain 1A-mutated cancers.

AT-rich interaction domain 1A (ARID1A) encodes a key component of the SWItch/Sucrose Non-Fermentable (SWI/SNF) chromatin remodeling complex that participates in gene expression. ARID1A alterations are quite common among cancer patients, although their role remains debated. The aim of this article was to study ARID1A-mutated cancer patients. Molecular and clinical data of cancer patients evaluated at Phase 1 Unit of Fondazione Policlinico Universitario A. Gemelli IRCCS were collected. Molecular analyses were performed using FoundationOne® CDx (Foundation Medicine Inc., Cambridge, MA, United States). Cancer patients with at least one molecular alteration in ARID1A gene were identified as ARID1A+. Among the 270 patients undergoing molecular analysis, we found 25 (9%) with at least one pathogenic alteration in ARID1A. The vast majority of these patients were female (84%). The median age at diagnosis was 59; most of the cancers (15, 60%) were gynecological (especially endometrioid endometrial cancers and clear cell ovarian cancers), diagnosed at an early stage. Frameshift alterations in ARID1A were the most common (19/31, 61%) alterations. The median number of mutations in ARID1A+ population was higher compared to ARID1A- population (6 vs. 4), as well as tumor mutational burden (TMB) [20 mutations/megabase (mut/Mb) vs. 1.26 mut/Mb]. Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA), phosphatase and tensin homolog (PTEN), catenin beta 1 (CTNNB1), and lysine methyltransferase 2D (MLL2) mutations were enriched in ARID1A+ population. In this cohort, ARID1A did not display any relation with response to platinum chemotherapy. Cancers with double alterations in ARID1A (ARID1A2+) were all gynecological cancers (83% endometrioid endometrial cancers). This analysis provides clinical and molecular details about the phenotypes of ARID1A+ cancers, in particular the subgroup of gynecologic cancers. The high frequency of concurrent mutations in the phosphoinositide 3-kinase (PI3K) pathway among endometrioid endometrial cancers may support the proposal of a new treatment strategy based on the combination of ataxia telangiectasia and Rad3-related (ATR) inhibitor and PIK3CA inhibitor.

Comparison of Mirena and Liletta levonorgestrel intrauterine devices for the treatment of endometrial intraepithelial neoplasia and grade 1 endometrioid endometrial cancer

ObjectiveCurrent standard nonsurgical management of endometrial intraepithelial neoplasia (EIN) and grade 1 endometrioid endometrial cancer (g1EEC) is the Mirena levonorgestrel intrauterine device (M−IUD). This retrospective study was designed primarily to determine noninferiority of the Liletta IUD (L-IUD) for pathologic regression of EIN and g1EEC compared to the M−IUD at 6 months of continuous use. Secondary objectives include to determine noninferiority as above at 3, 9, and 12 months of continuous use and to identify factors including DNA mismatch repair (MMR) status associated with pathologic regression after LNG-IUD use. MethodsA retrospective observational study was performed with patients treated for EIN or g1EEC and managed continuously with M- or L-IUD. Patients with recent (within 6 months) or concurrent progesterone use were excluded. For the EIN group, the noninferiority margin of odds ratio was predetermined to be 0.58, and for the g1EEC group it was 0.64. Results62 patients from an academic center and a safety-net hospital were identified with continuous M−IUD (n = 44) or L-IUD (n = 18) use for EIN or g1EEC. 85% of patients treated with L-IUD were from a safety-net hospital, which had 63% with public insurance. At 3/6/9 months, 54/71/73% of patients with M−IUD and 80/83/100% with L-IUD had pathologic regression of EIN (95% confidence interval of estimated odds ratio 1.00–2.07/0.84–2.03/0.69–2.10). Lifetime smoking status, not MMR status, was significantly associated with pathologic regression. ConclusionsL-IUD is an effective fertility-sparing treatment for EIN. L-IUD is noninferior to M−IUD for pathologic regression of EIN after 3,6, and 9 months. Further larger studies are warranted to validate findings in EIN and g1EEC.

Orlistat exerts anti-obesity and anti-tumorigenic effects in a transgenic mouse model of endometrial cancer.

Among all cancers, endometrial cancer is most strongly associated with obesity, with more than 65% of endometrial cancers attributable to obesity and being overweight. Fatty acid synthase (FAS), a key lipogenic enzyme, is expressed in endometrial cancer tumors and is associated with a worse prognosis for this disease. Orlistat, an FAS inhibitor, is an FDA-approved weight loss medication that has demonstrated anti-tumor activity in a variety of preclinical cancer models. In this study, the Lkb1fl/flp53fl/fl mouse model of endometroid endometrial cancer was exposed to three diet interventions, including a high fat diet (obese), a low fat diet (lean) and switch from a high fat to a low fat diet, and then exposed to orlistat or placebo. The mice fed a high-fat diet had significantly increased body weight and tumor weight compared to mice fed a low-fat diet. Switching from a high-fat diet to a low fat diet led to a reduction in mouse weight and suppressed tumor growth, as compared to both the high fat diet and low fat diet groups. Orlistat effectively decreased body weight in obese mice and inhibited tumor growth in obese, lean, and the high fat diet switch to low fat diet mouse groups through induction of apoptosis. Orlistat also showed anti-proliferative activity in nine of 11 primary cultures of human endometrial cancer. Our findings provide strong evidence that dietary intervention and orlistat have anti-tumor activity in vivo and supports further investigation of orlistat in combination with dietary interventions for the prevention and treatment of endometrial cancer.

Independent Tissue-Based Biomarkers in Endometrioid Endometrial Cancer: Tumor Budding in Microsatellite Instability and WHO Grading in Copy-Number-Low Patients.

The molecular characterization of endometrial endometrioid adenocarcinomas has provided major advances in its prognostic stratification. However, risk assessment of microsatellite instability (MSI) and copy-number (CN)-low cases remains a challenge. Thus, we aimed to identify tissue-based morphologic biomarkers that might help in the prognostic stratification of these cases. Histomorphologic parameters (WHO grading, tumor budding (TB), tumor-stroma ratio (as a quantitative description of stromal desmoplasia), tumor-infiltrating lymphocytes (TIL), "microcystic, elongated, fragmented" (MELF) pattern) were analyzed in resection specimens of the TCGA-UCEC cohort (n = 228). For each quantitative parameter, a two-tiered system was developed utilizing systematically determined cutoffs. Associations with survival outcomes were calculated in univariate and multivariate analysis and validated in two independent cohorts. In MSI tumors, only TB remained an independent prognostic factor. TB (≥3 buds/high-power field) was associated with inferior outcomes and with lymph node metastases. The prognostic significance of TB was confirmed in two validation cohorts. For CN-low tumors, established grading defined by the WHO was independently prognostic with inferior outcomes for high-grade tumors. The evaluation of TB might help in identifying MSI-patients with unfavorable prognosis who, e.g., could benefit from lymphadenectomy. WHO-based grading facilitates independent prognostic stratification of CN-low endometrioid adenocarcinomas. Therefore, we propose the utilization of TB and WHO-based grading, two tissue-based and easy-to-assess biomarkers, in MSI/CN-low endometrial carcinomas for improved clinical management.

Ipatasertib exhibits anti‑tumorigenic effects and enhances sensitivity to paclitaxel in endometrial cancer invitro and invivo.

Endometrial cancer is the most common gynecologic cancer and one of the only cancers for which incidence and mortality is steadily increasing. Although curable with surgery in the early stages, endometrial cancer presents a significant clinical challenge in the metastatic and recurrent setting with few novel treatment strategies emerging in the past fifty years. Ipatasertib (IPAT) is an orally bioavailable pan‑AKT inhibitor, which targets all three AKT isoforms and has demonstrated anti‑tumor activity in pre‑clinical models, with clinical trials emerging for many cancer types. In the present study, the MTT assay was employed to evaluate the therapeutic efficacy of IPAT or IPAT in combination with paclitaxel (PTX) in endometrial cancer cell lines and primary cultures of endometrial cancer. The effect of IPAT and PTX on the growth of endometrial tumors was evaluated in a transgenic mouse model of endometrial cancer. Apoptosis was assessed using cleaved caspase assays and cellular stress was assessed using ROS, JC1 and tetramethylrhodamine ethyl ester assays. The protein expression levels of markers of apoptosis and cellular stress, and DNA damage were evaluated using western blotting and immunohistochemistry. IPAT significantly inhibited cell proliferation, caused cell cycle G1 phase arrest, and induced cellular stress and mitochondrial apoptosis in a dose dependent manner in human endometrial cancer cell lines. Combined treatment with low doses of IPAT and PTX led to synergistic inhibition of cell proliferation and induction of cleaved caspase 3 activity in the human endometrial cancer cell lines and the primary cultures. Furthermore, IPAT effectively reduced tumor growth, accompanied by decreased protein expression levels of Ki67 and phosphorylation of S6 in the Lkb1fl/flp53fl/fl mouse model of endometrioid endometrial cancer. The combination of IPAT and PTX resulted in increased expression of phosphorylated‑H2AX and KIF14, markers of DNA damage and microtubule dysfunction respectively, as compared with IPAT alone, PTX alone or placebo‑treated mice. The results of the present study provide a biological rationale to evaluate IPAT and the combination of IPAT and PTX in future clinical trials for endometrial cancer.

The prognostic value of P53 index in predicting the recurrence of early low-risk endometrial cancer.

We aimed to clarify the clinical value of P53 index in patients with early low-risk endometrial cancer (EC) and find an optimal cut-off value of P53 index for predicting the recurrence of these patients. The clinicopathological data of 157 patients with early low-risk EC (stage 1A with grade 1 or 2 endometrioid EC) were analyzed. The optimal cut-off value of the P53 index was calculated by the receiver operating characteristic curve analysis and Youden index. Cox regression model was used to evaluate the independent prognostic predictors of recurrence of EC. Then all patients were divided into two groups according to the optimal cut-off value of the P53 index. Differences of the clinicopathological parameters between the two groups were compared. Multivariate analysis showed age PR (p = 0.020) and P53 (p = 0.001) were independent prognostic factors for the recurrence of EC. The value of P53 index was found to be the optimal cut-off point of 17.5% in estimating the recurrence of EC. The 5-year recurrence-free survival rates of patients in the low P53 index group (<17.5%) and the high P53 index group (≥17.5%) were 94.6% and 65.4% (p < 0.001). It has been revealed that the P53 index is a prognostic factor for recurrence in early low-risk EC. The optimal cut-off value of P53 index may contribute to the postoperative individualized treatment options for early low-risk EC patients.

Molecular Classification Predicts Response to Radiotherapy in the Randomized PORTEC-1 and PORTEC-2 Trials for Early-Stage Endometrioid Endometrial Cancer.

The molecular classification of endometrial cancer (EC) has proven to have prognostic value and is predictive of response to adjuvant chemotherapy. Here, we investigate its predictive value for response to external beam radiotherapy (EBRT) and vaginal brachytherapy (VBT) in early-stage endometrioid EC (EEC). Data of the randomized PORTEC-1 trial (n = 714) comparing pelvic EBRT with no adjuvant therapy in early-stage intermediate-risk EC and the PORTEC-2 trial (n = 427) comparing VBT with EBRT in early-stage high-intermediate-risk EC were used. Locoregional (including vaginal and pelvic) recurrence-free survival was compared between treatment groups across the four molecular classes using Kaplan-Meier's methodology and log-rank tests. A total of 880 molecularly classified ECs, 484 from PORTEC-1 and 396 from PORTEC-2, were included. The majority were FIGO-2009 stage I EEC (97.2%). The median follow-up was 11.3 years. No locoregional recurrences were observed in EC with a pathogenic mutation of DNA polymerase-ε (POLEmut EC). In mismatch repair-deficient (MMRd) EC, locoregional recurrence-free survival was similar after EBRT (94.2%), VBT (94.2%), and no adjuvant therapy (90.3%; P = .74). In EC with a p53 abnormality (p53abn EC), EBRT (96.9%) had a substantial benefit over VBT (64.3%) and no adjuvant therapy (72.2%; P = .048). In EC with no specific molecular profile (NSMP EC), both EBRT (98.3%) and VBT (96.2%) yielded better locoregional control than no adjuvant therapy (87.7%; P < .0001). The molecular classification of EC predicts response to radiotherapy in stage I EEC and may guide adjuvant treatment decisions. Omitting radiotherapy seems to be safe in POLEmut EC. The benefit of radiotherapy seems to be limited in MMRd EC. EBRT yields a significantly better locoregional recurrence-free survival than VBT or no adjuvant therapy in p53abn EC. VBT is the treatment of choice for NSMP EC as it is as effective as EBRT and significantly better than no adjuvant therapy for locoregional tumor control.

Intra-racial disaggregation reveals associations between nativity and overall survival in women with endometrial cancer

ObjectivePrior studies have demonstrated survival differences between Black women with endometrial cancer (EC) born in the US and Caribbean. Our objective was to determine if country of birth influences EC overall survival (OS) in disaggregated subpopulations of Black women. MethodsUsing the Florida Cancer Data System, women with EC diagnosed from 1981 to 2017 were identified. Demographic and clinical information were abstracted. Women who self-identified as Black and born in the US (USB), Jamaica (JBB), or Haiti (HBB) were included. Statistical analyses were performed using chi-square, Cox proportional hazards models, and Kaplan-Meier methods with significance set at p < 0.05. Results3817 women met the inclusion criteria. Compared to USB, JBB and HBB had more high-grade histologies, more advanced stage disease, had a greater proportion of uninsured or Medicaid insured, and had a higher proportion of women who received chemotherapy (all p < 0.05). In multivariate analyses, age (HR 1.03 [1.02–1.05]), regional stage (HR 1.52 [1.22–1.89]), distant stage (HR 3.73 [2.84–4.89]), lymphovascular space invasion (HR 1.96 [1.61–2.39]), receipt of surgery (HR 0.47 [0.29–0.75]), and receipt of chemotherapy (HR 0.77 [0.62–0.95]) were independently associated with OS. Compared to USB, Haitian nativity was an independent negative predictor of OS when evaluating all histologies together (HR 1.54 [1.18–2.00]) and for endometrioid EC specifically (HR 1.77 [1.10–2.83]). Among women with serous EC, HBB had markedly worse median OS (18.5 months [13.4–46.5]) relative to USB (29.9 months [26.3–35.9]) and JBB (41.0 months, [34.1–82.6], p = 0.013). ConclusionCountry of birth is associated with endometrial cancer survival in Black women, with HBB demonstrating worse outcomes.

Retrospective Analysis of the Correlation of MSI-h/dMMR Status and Response to Therapy for Endometrial Cancer: RAME Study, a Multicenter Experience.

There is poor evidence regarding sensitivity to chemotherapy in endometrial cancer (EC) based on microsatellite instability (MSI)/mismatch repair (MMR) status. The RAME study is a retrospective analysis aiming to assess response to chemotherapy in MSI-high (h)/deficient (d) MMR and MSI-low (l)/proficient (p) MMR EC patients. Primary endpoints were recurrence-free survival (RFS) for patients with localized disease and progression-free survival (PFS) and overall survival (OS) in patients with advanced/recurrent disease. A total of 312 patients treated between 2010 and 2022 in four high-volume Multicenter Italian Trial in Ovarian cancer and gynecological malignancies (MITO) centers were selected. In total, 239 patients had endometrioid EC (76.6%), 151 had FIGO stage I at diagnosis (48.9%) and 71 were MSI-h/dMMR (22.8%). Median age was 65 (range 31-91) years. Among patients with localized disease, median RFS was 100.0 months (95% CI 59.4-140.7) for MSI-l/pMMR and 120.9 months (60.0-181.8) for MSI-h/dMMR (p = 0.39). Seventy-seven patients received first-line chemotherapy for advanced/recurrent disease. Patients with MSI-h/dMMR ECs had a significantly worse OS (p = 0.039). In patients receiving platinum-based chemotherapy, no statistically significant differences in PFS (p = 0.21) or OS (p = 0.057) were detected, although PFS and OS were numerically longer in the MSI-l/pMMR population. Patients with metastatic MSI-h/dMMR EC receiving first-line chemotherapy had a significantly worse OS.

Ovarian preservation in gynecologic oncology: current indications and techniques.

Early menopause represents a relevant clinical issue for women. Nevertheless, this issue should be balanced with the risks of ovarian metastasis, ovarian recurrence, and the risk of recurrence in hormone-sensitive gynecological cancers. The purpose of this review was to provide an overview on current indications and techniques of ovarian preservation in patients with gynecological cancers. The potential discussion about ovarian conservation could be proposed to patients with FIGO-stage IA grade 1-2 endometrioid endometrial cancer aged 40 years or less, FIGO-stage IB1-IB2 node-negative cervical cancer with squamous cell carcinoma and HPV-associated adenocarcinoma, FIGO-stage IA-IC grade 1-2 serous, endometrioid, mucinous expansile pattern ovarian cancer, any stage germ cell ovarian tumors, and FIGO-stage IA sex cord-stromal tumors. Technique to perform ovarian transposition in cervix cancer is also reported. Ovarian conservation is a surgical approach that involves preserving one or both ovaries during the treatment of gynecologic cancers. This approach has gained popularity in recent years, as it offers several benefits to the patient, including the preservation of hormonal function and fertility. The decision to perform ovarian conservation depends on several factors, such as the stage and type of cancer, the patient's age, fertility desire, and should be carefully discussed with patients.

Surgical and oncologic outcomes in surgically treated women 80 years and older with endometrioid endometrial cancer as a function of their comorbidities

ObjectiveTo describe the surgical and oncologic outcomes in surgically treated oldest old women (≥80 years) with endometrioid endometrial cancer as a function of their comorbidities. MethodsIn this retrospective cohort study, patients aged 80–99 years who underwent surgical management of stage I endometrioid endometrial cancer between 2006 and 2018 were included. Low- and high-intermediate risk disease was defined using the Gynecologic Oncology Group-99 criteria. The validated, Combined Age-Charlson Comorbidity Index (CA-CCI) was used to quantify comorbidity burden. Logistic regression was used to identify the independent predictors of various surgical and oncologic outcomes. Kaplan-Meier survival analysis was performed to compare survival distributions based on mortality cause and comorbidity status. ResultsWe identified 64 women who met the eligibility criteria. Median age was 84 years (IQR 80, 94 years). Among oldest old women undergoing a hysterectomy with or without lymph node dissection, women with a CA-CCI score of ≥7 had an 8 times higher risk of postoperative infections compared with oldest old women with a <7 score (95% CI 1.53–48.91, P = 0.015). Women with a CA-CCI score of ≥8 were 45% less likely to survive at 3 years (aRR 0.55, 95% CI 0.004–0.87; P = 0.039) than those with a lower CA-CCI score (three-year overall survival 73% vs 96%). ConclusionSurgical and oncologic outcomes in oldest old women with early stage endometrioid endometrial cancer are largely determined by comorbidity status. Less comorbid women (CA-CCI score < 8) had a significantly higher five-year survival at 87% than their more comorbid counterparts. Use of age-comorbidity risk scoring such as CA-CCI, preoperative optimization, and careful selection for and counseling of patients about surgical treatment are paramount in providing optimal recovery and survival advantages in the oldest old.

Rapid identification of endometrial hyperplasia and endometrial endometrioid cancer in young women

PurposeWe investigated endometrial hyperplasia (EH) and endometrial endometrioid cancer (EEC) and developed a nomogram model to predict the EH/EEC risk and improve patients’ clinical prognosis.MethodsData were collected from young females (age: ≤ 40 years) who complained of abnormal uterine bleeding (AUB) or abnormal ultrasound endometrial echoes. The patients were randomly divided into training and validation cohorts at a 7:3 ratio. The risk factors for EH/EEC were determined through the optimal subset regression analysis and a prediction model was developed. We used the concordance-index (C-index), and calibration plots in the training and validation sets to assess the prediction model. We drew the ROC curve in the validation set and calculated the area under the curve (AUC), as well as its accuracy, sensitivity, specificity, negative predictive value, and positive predictive value, and finally, converted the nomogram into a web page dynamic nomogram.ResultsPredictors included in the nomogram model were body mass index (BMI), polycystic ovary syndrome (PCOS), anemia, infertility, menostaxis, AUB type, and endometrial thickness. The C-index of the model in the training and validation sets were 0.863 and 0.858. The nomogram model had good discriminatory power and was well-calibrated. According to the prediction model, the AUC of EH/EC, EH without atypia, and AH/EC were 0.889, 0.867, and 0.956, respectively.ConclusionsThe nomogram of EH/EC is significantly associated with risk factors, namely BMI, PCOS, anemia, infertility, menostaxis, AUB type, and endometrial thickness. The nomogram model can be used to predict the EH/EC risk and rapidly screen risk factors in a women population with high risk.

P7 Is mismatch repair status prognostic of clinical outcomes in patients with early stage endometrioid endometrial cancer?

P7 Is mismatch repair status prognostic of clinical outcomes in patients with early stage endometrioid endometrial cancer?

A novel epithelial-mesenchymal transition-related lncRNA signature predicts prognosis and immune status in endometrioid endometrial cancer.

The pathogenesis and progression of endometrial cancer (EC) are associated with epithelial-mesenchymal transition (EMT) and long noncoding RNAs (lncRNAs). In the present study, we aimed to identify an EMT-related lncRNA signature and evaluate its prognostic value in EC. We obtained the expression profile of lncRNAs and clinical information of patients with endometrioid EC from The Cancer Genome Atlas database (N = 401). We identified a signature of 5 EMT-related lncRNAs and calculated the risk score of each patient. Next, we validated the independence of the prognostic value of the EMT-related lncRNA signature. Furthermore, we performed Gene Set Enrichment Analysis to identify potential molecular function and Kyoto Encyclopedia of Genes and Genomes pathways related to the EMT-related lncRNA signature. Tumor microenvironment analysis and immune checkpoint blockade (ICB) response prediction were also assessed. Survival analysis revealed that the high-risk group, based on the EMT-related lncRNA signature, had a poorer prognosis than the low-risk group in the training, testing, and entire sets. The predictive value of the EMT-related lncRNA signature was independent of age, The International Federation of Gynecology and Obstetrics stage, tumor grade, and body mass index. Time-dependent receiver operating characteristic curves also demonstrate the prognostic accuracy of this risk model. Gene Set Enrichment Analysis showed that cytokine-cytokine receptor interaction, glycolysis/gluconeogenesis, and IL-17 signaling pathway were significantly enriched. Furthermore, tumor microenvironment analysis indicated a significant negative correlation between the immune score and EMT-related lncRNA signature risks core, while the low-risk group was more likely to respond to ICB therapy than the high-risk group. A reliable EMT-related lncRNA signature of endometrioid EC was identified that could be utilized as an independent prognostic biomarker to predict patient survival outcomes and provide references for the option of ICB therapy.

Endometrial cancer risk and trends among distinct African descent populations.

Endometrial cancer (EC) is the fourth most common cancer among Black women in the United States, a population disproportionately affected by aggressive nonendometrioid subtypes (e.g., serous, carcinosarcoma). To examine EC vulnerability among a wider spectrum of African descent populations, a comparison between Black women residing in different countries, rather than in the United States alone, is needed. The authors analyzed 34,789 EC cases from Florida (FL) (2005-2018), Martinique (2005-2018), and Guadeloupe (2008-2018) based on cancer registry data. Age-adjusted incidence rates, incidence rate ratios (IRRs), and annual percent changes (APC) in trends were estimated for Black populations residing in the United States (non-Hispanic Blacks [NHB]) and Caribbean. The US non-Hispanic White (NHW) population was used as a reference. Caribbean Black women had the lowest rates for endometrioid and nonendometrioid subtypes. Nonendometrioid types were most common among US (FL) NHBs (9.2 per 100,000), 2.6 times greater than NHWs (IRR, 2.60; 95% confidence interval [CI], 2.44-2.76). For endometrioid EC, rates increased 1.8% (95% CI, 0.1-3.5) yearly from 2005 to 2018 for US (FL) NHBs and 1.2% (95% CI, 0.9-1.6) for US (FL) NHWs whereas no change was observed for Caribbean Blacks. For nonendometroid carcinomas, rates increased 5.6% (95% CI, 4.0-7.2) among US (FL) NHB, 4.4% (95% CI, 0.3-8.6) for Caribbean Black, and 3.9% for US (FL) NHW women (95% CI, 2.4-5.5). Lower rates of nonendometrioid EC among Caribbean Black women suggest that vulnerability for these aggressive tumor subtypes may not currently be an overarching African ancestry disparity. Most importantly, there is an alarmingly increasing trend in nonendometrioid across all populations studied, which warrants further surveillance and etiological research for this particular subtype. We analyze population-based incidence rates and trends of endometrial cancer (EC) for African descent populations residing in different countries (i.e., United States, Martinique, Guadeloupe) to examine whether EC vulnerability among Black women is socio-environmental or more ancestry-specific in nature. The increased EC risk was not uniform across all Black women since the Caribbean had the lowest rates (for endometrioid and nonendometrioid histology subtypes). Regardless, from 2005 to 2018, there was an increasing trajectory of nonendometrioid EC for all groups, regardless of race.