Incidence Of Endometrial Cancer Research Articles

Trends in incidence and hormonal management of endometrial cancer during potentially reproductive age in Japan: a population-based study.

We aimed to investigate the trends in the incidence and treatment of endometrial cancer (EC) during potentially reproductive age in Japan, with a special focus on the relative oncologic safety of hormonal therapy (HT) over surgery. This population-based retrospective cohort study was conducted using data from the Osaka Cancer Registry from 2004 to 2018. Women with EC were first identified and then distributions of age, stage, histology, and initial treatment were examined. Then, the relative oncologic safety of HT over surgery in patients under the age of 50years was evaluated. Among the 9417 patients with EC, 1937 were diagnosed during their potentially reproductive age (< 50years). The incidence of EC during potentially reproductive age has increased from 18.5% in 2004-2011 to 21.9% in 2012-2018. ECs during potentially reproductive age more frequently displayed favorable characteristics, such as endometrioid histology, and lower histological grade than those in non-potentially reproductive age. Among the 1223 patients diagnosed with localized endometrioid EC, 74 cases (6.0%) received HT as an initial treatment, while 1100 cases (90.0%) underwent surgery as their initial treatment. When the two treatment groups were compared, there was no significant difference in overall survival (p = 0.3713). The estimated 5-year survival rates were 100 and 98.8% in the HT and surgery groups, respectively. EC is increasingly diagnosed during potentially reproductive age in Japan. The use of HT as an initial treatment is increasing, and achieved comparable survival outcomes to urgery against localized endometrioid EC during the potentially reproductive age.

Occult endometrial cancer in women undergoing hysterectomy for benign indications: a retrospective cohort study in a tertiary hospital in China.

To evaluate the feasibility of further reducing the incidence of occult endometrial cancer in women undergoing hysterectomy for benign gynecological indications. Patients who underwent hysterectomies for presumed benign gynecologic conditions at Peking Union Medical College Hospital were retrospectively identified. Patients with occult endometrial cancer, which was defined as endometrial cancer diagnosed on postoperative histopathology with no preoperative confirmed malignancy, were selected. 24/7558 (0.32%; 95% CI 0.20-0.47%) patients undergoing hysterectomy for benign indications had occult endometrial cancer. Asymptomatic patients with normal endometrial imaging all tended to have favorable pathology. Heavy menstrual bleeding was the most overlooked AUB pattern in the premenopausal group. In the postmenopausal group, all the patients with serous adenocarcinoma or G3 endometrioid adenocarcinoma histology/stage T1b disease/LVSI space invasion had a history of persistent or recurrent PMB ≥ 6months and/or an intracavitary lesion > 20mm in diameter. 3/4 of the samples of the postmenopausal patients did not have adequate endometrium for evaluation. To further reduce the incidence of occult endometrial cancer, physicians should focus on the patient's bleeding pattern and actively implement endometrial sampling whenever indicated. Transvaginal ultrasonography is a valuable preoperative evaluation. Hysteroscopy with directed biopsy is the preferred procedure in postmenopausal patients.

Development and Potential Implementation of Endometrial Cancer Screening in a Poor-Prognosis Endemic Cancer Community [ID 2683642

INTRODUCTION: Endometrial cancer incidence and mortality both are increasing in the United States. Certain patient populations are disproportionately affected by this disease. Currently, there is no recommendation from any professional society to screen high-risk patients for premalignancy or cancer. Our patient population is composed of predominantly Black women, a group that experiences worse endometrial cancer outcomes than other demographics. A risk assessment nomogram may be able to be developed using data from this unique patient population that can identify women at high risk of developing endometrial disease. METHODS: Endometrial pathology specimens collected at a large safety-net hospital between the years of 2013 and 2022 were analyzed. A retrospective chart review was performed on this data, looking for the patient characteristics of race, age, body mass index (BMI), parity, hemoglobin A1C level, and tamoxifen use history at the time of specimen collection. Odds ratios were calculated for those variables individually as well as collectively to determine whether they could be used to predict risk of endometrial disease in a woman with some of all those characteristics. RESULTS: The odds ratios for age, BMI, and parity were statistically significant between benign and abnormal pathologic specimens. The area under the receiver operating characteristic curve was 0.76 when combining age, BMI, and parity. CONCLUSION: Our data suggest that at-risk patients can be reliably identified using simple characteristics. Strengths of our study include a unique patient population and large database. Future directions include refinement of the model and prospective application in the clinical setting.

Impact of hormonal contraception on endometrial histology in patients with Lynch syndrome, a retrospective pilot study.

Hormonal contraception (HC) is a well-recognized protection against endometrial cancer (EC) in the general population. It has not been established if this is also applicable to women with Lynch syndrome (LS), a condition associated with a up to 50% lifetime risk of developing EC. The objective of this study was to evaluate if the use of HC influences the incidence of endometrial hyperplasia and EC in women with LS by comparing the histology of annual endometrial biopsies obtained in patients with LS who are using HC versus non-users. This is a retrospective cohort study conducted with endometrial biopsies obtained in women 30 to 50 years of age with LS. The Pearson Chi-square test was performed to compare the prevalence of cancer and hyperplasia in the HC users and in the non-HC users groups. A total of 164 endometrial biopsies obtained among 75 women were suitable for analysis. Among the 86 biopsies obtained in the non-HC group, 81.4% (70/86) were normal. Two cases of endometrial carcinoma (2.3%) and 6 endometrial hyperplasia without atypia were found (7.0%). Among the 78 biopsies performed in patients using HC, 78.2% (61/78) were normal. Three endometrial hyperplasia without atypia (3.8%) and three cases of EC were diagnosed (3.8%). This study suggests that, in women of 30 to 50 years of age with LS, the use of hormonal contraception does not seem to decrease the occurrence of endometrial hyperplasia/carcinoma on annual endometrial histology.

Abstract 2168: Intermittent fasting in combination with carboplatin in a pre-clinical model of obesity-driven endometrial cancer

Abstract Objectives: Endometrial cancer (EC) incidence and mortality continue to rise, with obesity a well-known driver of this disease. Obesity is associated with excess estrogen, hyperinsulinemia, activation of the Akt/mTOR pathway, chronic inflammation, and a heightened capacity to harvest dietary energy, all of which contribute to the development and progression of EC. Intermittent energy restriction (IER) is thought to have anti-tumorigenic benefits and has been shown to have synergistic effects with chemotherapy and hormonal therapy in various cancer types. Thus, we evaluated the anti-tumorigenic effects of a switch from high fat diet (HFD) to either IER or low fat diet (LFD) with carboplatin treatment in a mouse model of obesity-driven endometrioid EC. Methods: Lkb1fl/flp53fl/fl mice were fed either HFD or LFD starting at 4 weeks of age. At 12 weeks of age, the HFD-fed mice were randomized to three treatment groups: continuous HFD, HFD-LFD switch, and HFD-IER switch. The LFD-fed mice were continuously maintained on LFD. At 16 weeks of age, all mice were injected with AdCre into the left uterine horn to induce EC development. At 26 weeks of age, mice were treated with placebo or carboplatin (50 mg/kg intraperitoneally weekly) for 4 weeks (n=8-10 mice per group). EC incidence, tumor weight, and body weight were evaluated. EC gene expression was assessed by microarray analysis. Results: EC incidence was lowest in the HFD-IER group (~60%) and highest in the HFD group (~80%); rates were similar in the other diet groups (~75%). The continuous HFD-fed mice demonstrated a 76% increase in tumor size relative to continuous LFD-fed mice (p&amp;lt;0.001). At sacrifice and after carboplatin treatment, mean body weights were significantly higher (p&amp;lt;0.05) in the HFD group (38g) than groups receiving continuous LFD (26g), HFD-LFD switch (28g), or HFD-IER switch (21g), although mean body weights were not significantly different within diet groups between placebo and carboplatin-treated mice. In placebo-treated groups, mean tumor weights were significantly lower in mice fed continuous LFD (0.62g), HFD-LFD switch (0.60g) and HFD-IER switch (0.26g) relative to continuous HFD-fed mice (1.10 g; p&amp;lt;0.001). When comparing gene expression between the HFD-LFD and the HFD-IER placebo groups, genes related to cholesterol metabolism, estrogen response, and inflammation were preferentially up-regulated in the HFD-IER group. Carboplatin treatment reduced EC tumor size 42-69% across all diet groups (p&amp;lt;0.05); tumor size was the smallest in the HFD-IER group (0.15g) relative to mice receiving continuous HFD (0.34g), HFD-LFD (0.29g) or continuous LFD (0.34g). Conclusion: IER with carboplatin treatment may be an innovative combination treatment strategy in the management of EC, a highly obesity-driven cancer. Citation Format: Jennifer Haag, Olivia Lara, Chunxiao Zhou, Stephen D. Hursting, Victoria Bae-Jump. Intermittent fasting in combination with carboplatin in a pre-clinical model of obesity-driven endometrial cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2168.

Mechanism of regulation of KIF23 on endometrial cancer cell growth and apoptosis

ObjectiveThe global incidence of endometrial cancer, a malignant tumor in females, is on the rise. It is one of the most common gynecological cancers. Early-stage endometrial cancers can often be treated successfully with uterine extirpation. However, those diagnosed at a later stage have a poor prognosis and encounter treatment challenges. Therefore, additional research is necessary to develop primary prevention strategies for high-risk women and improve survival rates among patients with endometrial cancer. Hence, gene therapy targeting KIF23 shows promise as an advanced strategy for the treatment of endometrial cancer.MethodsImmunohistochemistry, Western blotting, and PCR were used to examine the expression of KIF23 and its associated pathway factors in endometrial cancer tissue (specifically Ishikawa and SNGM cells, respectively). We investigated the functional roles of KIF23 using CCK-8, colony-forming proliferation assays, Transwell migration assays, and xenotransplantation in mice.ResultsImmunohistochemistry analysis showed variations in the expression levels of KIF23 between endometrial cancer tissue and normal endometrium tissue. KIF23 downregulated BAX and caspase-3 protein expression while upregulating BCL-2 protein expression. Additionally, knocking out KIF23 inhibits endometrial cancer cell proliferation and migration while promoting cell death. Mechanistically, our study provides evidence that KIF23 promotes endometrial cancer cell proliferation by activating the ERK and AKT/PI3K pathways, while simultaneously inhibiting programmed cell death in endometrial cancer.ConclusionOur study provides evidence to support the inhibition of endometrial cancer by KIF23 knockdown. This offers valuable insights for future research on potential therapeutic strategies for this type of cancer.Graphical

Biomarkers in the Diagnosis of Endometrial Precancers. Molecular Characteristics, Candidate Immunohistochemical Markers, and Promising Results of Three-Marker Panel: Current Status and Future Directions.

Endometrial carcinoma stands as the most prevalent gynecological cancer and the fourth most common cancer affecting women. The incidence of endometrial cancer has been steadily increasing over the past decade, posing a significant threat to public health. The early detection of its precancers remains a critical and evolving concern to reduce mortality associated with endometrial carcinoma. In the last decade, our understanding of endometrial carcinoma and its precancers has advanced through systematic investigations into the molecular genetics of endometrial carcinoma and its precancers. In this review, we focus on advances in precancers associated with the endometrioid subtype, by far the most common histologic variant of endometrial adenocarcinoma. Recent investigations have led to the identification of new biomarkers, and the proposed incorporation of these biomarkers or biomarker panels into the diagnostic framework of endometrial carcinoma precancers. Here, we review these recent advances and their relevance to the histopathologic diagnosis of endometrial carcinoma precancers.

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.

Overweight and obese women’s symptoms, knowledge, and preferences regarding endometrial biopsy for endometrial cancer detection: A threshold technique survey

BackgroundThe incidence of endometrial cancer (EC) in the United States continues to rise, driven mainly by the obesity epidemic. We sought to determine overweight and obese women’s cancer risk knowledge and preferences regarding diagnostic endometrial biopsy (EMB) for EC detection. MethodsAn online survey was administered to overweight and obese women without EC recruited through the electronic medical record’s online patient portal. Baseline questions queried gynecologic history, cancer risk knowledge, and factors potentially influencing decision-making for EMB. We used the threshold survey technique to identify the minimum acceptable risk (MAR) threshold at which each respondent would be willing to undergo an EMB to detect EC. ResultsOf 357 respondents (median age 45 years (interquartile range [IQR]: 38–54); median BMI 39 [IQR: 36.0–44.6]), fewer than half (48.7 %) were aware that obesity is a risk factor for EC, and 10 % considered their risk of EC to be high. Almost half (42 %) of respondents reported MAR thresholds characterized as very low (0–1 %), and these were more common among respondents with higher BMIs. Forty percent identified their weight as a factor influencing their MAR threshold decision, while 76 % identified their perceived personal risk as a factor. Less than half cited immediate risks of the procedure. ConclusionMany patients reported being willing to undergo an EMB at very low risk thresholds for EC. Perceived personal risk is a stronger factor in decision-making than immediate procedural risks. Providers should focus on communicating patients’ risk to motivate EMB to detect EC where appropriate.

Abstract A008: Intermittent fasting in combination with PD-inhibitor treatment as an innovative treatment strategy in a pre-clinical model of obesity-driven endometrial cancer

Abstract Objective: Endometrial cancer (EC) incidence and mortality continue to rise, with obesity a well-known driver of this disease. Obesity is associated with excess estrogen, hyperinsulinemia, activation of the Akt/mTOR pathway, chronic inflammation and a heightened capacity to harvest dietary energy, which all contribute to the development and progression of EC. Intermittent energy restriction (IER) is thought to have anti-tumorigenic benefits and has been shown to have synergistic effects with chemotherapy and hormonal therapy in various cancer types. IER may also promote anti-tumor immune responses by stimulating CD4+ and CD8+ cells, making this dietary strategy an innovative therapeutic partner with PD-1 inhibitors, which are commonly used in EC. Thus, we evaluated the anti-tumorigenic effects of a switch from high fat diet (HFD) to either IER or low-fat diet (LFD) with PD-1 inhibitor treatment in a mouse model of obesity-driven endometrioid EC. Methods: Lkb1fl/flp53fl/fl mice were fed either HFD or LFD starting at 4 weeks of age. At 12 weeks of age, the HFD-fed mice were randomized to three treatment groups: HFD, HFD-LFD switch or HFD-IER switch. The LFD-fed mice were maintained on LFD. At 16 weeks of age, all mice were injected with AdCre into the left uterine horn to induce EC development. At 26 weeks of age, mice were treated with placebo or a mouse PD-1 inhibitor (BioXCell) (10mg/kg, 2 times/wk, intraperitoneal) for 4 wks (N=8-10 mice per group). RNAseq was performed to determine differences in immune pathways between ECs of obese and lean mice. CD4+ and CD8+ T cells in tumors of obese and lean mice were evaluated by flow cytometry. Results: Obesity resulted in a 52% increase in tumor size, comparing obese versus lean mice (p&amp;lt;0.05). Expression of genes related to T-cell/B-cell receptors, NF-kappa B and TNF pathways were upregulated in the ECs of obese versus lean mice. PD-1 inhibitor therapy increased PD-1 expression on CD4+ and CD8+ T cells in both obese and lean ECs. In addition, PD-1 inhibitor treatment led to an increase in percentage of CD4+ T cells in obese and lean ECs but increased the percentage of CD8+ T cells in only lean ECs. At sacrifice and after PD-1 inhibitor treatment, mean body weights were significantly higher (p&amp;lt;0.05) in the HFD group (42g) than groups receiving LFD (29g), HFD-LFD switch (34g) or HFD-IER switch (23g). EC incidence was lowest in the HFD-IER group (~61%) and highest in the HFD group (~80%); rates were similar in the other diet groups (~75%). In placebo-treated groups, mean tumor weights were significantly lower in mice fed LFD (0.45g), HFD-LFD switch (0.41g) and HFD-IER switch (0.29g) relative to continuous HFD-fed mice (0.94g; p=0.001-0.05). PD-1 inhibitor treatment reduced EC size 24-68% across all diet groups (p=0.05-0.001); size reduction was greatest in the HFD-IER group (0.18g) relative to mice receiving continuous HFD (0.30g), HFD-LFD (0.31g) or LFD (0.31g). Conclusion: IER with PD-1 inhibitor treatment may be an innovative strategy in the management of EC, a highly obesity-driven cancer. Citation Format: Jennifer Haag, Olivia Lara, Chunxiao Zhou, Stephen D. Hursting, Victoria Bae-Jump. Intermittent fasting in combination with PD-inhibitor treatment as an innovative treatment strategy in a pre-clinical model of obesity-driven endometrial cancer [abstract]. In: Proceedings of the AACR Special Conference on Endometrial Cancer: Transforming Care through Science; 2023 Nov 16-18; Boston, Massachusetts. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(5_Suppl):Abstract nr A008.

Abstract IA011: Understanding field carcinogenesis in obesity-related endometrial cancer

Abstract Over the last decade, endometrial cancer (EC) incidence has increased at an average rate of 0.8% each year. Although cancer death rates decreased during this time, EC showed the greatest increase in cancer death among women. Public awareness of EC remains low, and EC research remains underfunded relative to its societal burden. While most women with EC are post-menopausal, up to 30% of cases occur in pre-menopausal women under 50 years of age, with obesity being a major risk factor. More than half of all EC is associated with obesity. Obesity is also a leading risk factor for benign endometrial hyperplasia, which is considered the precursor lesion to EC. Like other cancers, the causes of EC are multifactorial, with obesity and somatic mutations playing causal roles. By 2030, half of all adult women in the U.S. are expected to be classified as obese. Therefore, EC incidence is expected to increase. If detected early, EC can be cured with surgical hysterectomy, but this solution is not ideal for all women. Intentional weight loss can lower endometrial cancer risk in obese women, but certain barriers prevent obese, at-risk women from losing weight or maintaining healthy lifestyles while living in obesogenic environments. There is a critical need to understand the biological mechanisms underlying EC pathogenesis in at-risk obese women. Although EC is thought to arise from a hyperplastic endometrial epithelium, our previous findings suggest that high-fat diet induced obesity affects other cell types within the endometrial microenvironment, including endometrial stroma and immune cells, in the absence of histopathological change. Common EC somatic mutations can also arise in the absence of histopathological change or occur in cases of benign disease. Our overarching hypothesis is that a normal appearing endometrium may accrue cell-context dependent alterations in response to obesity and somatic mutations across a pre-malignant tissue field that are predictive of malignant transformation. This presentation will highlight our recent work on the combined molecular and phenotypic effects of obesity and common EC driver mutations on the endometrial tissue field. The identification of high-value molecular targets across the endometrial pre-malignant field may inform new early detection and prevention strategies for EC. Citation Format: Ronald Chandler. Understanding field carcinogenesis in obesity-related endometrial cancer [abstract]. In: Proceedings of the AACR Special Conference on Endometrial Cancer: Transforming Care through Science; 2023 Nov 16-18; Boston, Massachusetts. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(5_Suppl):Abstract nr IA011.

Trends in the incidence and survival outcomes of endometrial cancer in Korea: a nationwide population-based cohort study.

To evaluate trends in the incidence and survival outcomes of endometrial cancer (EC) based on the year of diagnosis, stage, age, and histologic types. Women with primary EC diagnosed between 1999 and 2018, and who were followed up with until 2019, were identified from the Korea Central Cancer Registry using the International Classification of Diseases, 10th revision. The age-standardized rates (ASRs) of incidence, annual percent changes (APCs), and survival were estimated according to age, stage, histology, and year of diagnosis. The ASR for EC increased from 2.38 per 100,000 in 1999 to 7.29 per 100,000 in 2018 across all histologic types (APCs of 9.82, 15.97, and 7.73 for endometrioid, serous, and clear cell, respectively, p<0.001). There were significant differences in the 5-year survival rates based on histology (90.9%, 55.0%, and 68.5% for endometrioid, serous, and clear cell, respectively, p<0.001), stage (93.4%, 77.0%, and 31.0% for localized, regional, and distant, respectively, p<0.001), and age (93.0% for <50 years and 80.6% for ≥50 years, p<0.001). The 5-year survival was significantly better in the group diagnosed between 2000 and 2018 (85.9%) than that in the 1999-2008 group (83.3%) (p<0.001). This trend was only observed for endometrioid cancer (p<0.001). The incidence of EC increased across the all 3 subtypes. Survival of patients with endometrioid histology improved over the past two decades, but remained static for serous or clear cell histology. Healthcare strategies to prevent EC incidence in at-risk populations and apply effective treatments for high-risk histology are needed.

Development of a long term, ex vivo, patient-derived explant model of endometrial cancer.

Incidence of endometrial cancer (EC) is rising in the developed world. The current standard of care, hysterectomy, is often infeasible for younger patients and those with high body mass index. There are limited non-surgical treatment options and a lack of biologically relevant research models to investigate novel alternatives to surgery for EC. The aim of the present study was to develop a long-term, patient-derived explant (PDE) model of early-stage EC and demonstrate its use for investigating predictive biomarkers for a current non-surgical treatment option, the levonorgestrel intra-uterine system (LNG-IUS). Fresh tumour specimens were obtained from patients with early-stage endometrioid EC. Tumours were cut into explants, cultured on media-soaked gelatin sponges for up to 21 days and treated with LNG. Formalin-fixed, paraffin embedded (FFPE) blocks were generated for each explant after 21 days in culture. Tumour architecture and integrity were assessed by haematoxylin and eosin (H&E) and immunohistochemistry (IHC). IHC was additionally performed for the expression of five candidate biomarkers of LNG resistance. The developed ex vivo PDE model is capable of culturing explants from early-stage EC tumours long-term (21 Days). This model can complement existing models and may serve as a tool to validate results obtained in higher-throughput in vitro studies. Our study provides the foundation to validate the extent to which EC PDEs reflect patient response in future research.

Study of Serum Copper and Zinc Levels and Serum Cu/Zn Ratio among Polish Women with Endometrial Cancer.

Micronutrients are important components for the homeostasis of the human body. The studies available in the literature of the subject on their impact on the risk of population diseases, including malignant neoplasms, are ambiguous. In this paper, the relationship between Cu and Zn serum levels and the occurrence of endometrial cancer have been analyzed. 306 patients (153 test group and 153 control group) matched for age were analyzed for Cu and Zn levels. Microelements levels were determined for sera collected during the hospitalization of patients by means of an inductively coupled plasma mass spectrometry. In addition, the Cu/Zn ratio in the population included in the study was analyzed. Univariable and multivariable analyzes were used to examine the relationship between the factors under study and the incidence of endometrial cancer. Lower levels of elements were observed in the study group compared with the control group (Cu: 959.39 μg/L vs. 1176.42 μg/L, p < 0.001; Zn: 707.05 μg/L vs. 901.67 μg/L, p < 0.001). A statistically significant relationship with the occurrence of endometrial cancer was observed for Cu and Zn. The patients with the lowest Cu level had a significantly higher occurrence of endometrial cancer compared with reference tertile (OR 8.54; p < 0.001). Similarly, compared with the reference tertile, the patients with the lowest Zn levels had a significantly greater incidence of endometrial cancer (OR 15.0; p < 0.001). The results of the study suggest an association of endometrial cancer occurrence with lower Cu and Zn serum levels.

Risk of Breast Cancer After Diabetes in Pregnancy: A Population-based Cohort Study

ObjectivesDiabetes is associated with an increased risk of several cancers, including postmenopausal breast cancer. The evidence for higher breast cancer risk after diabetes in pregnancy is conflicting. We compared the incidence of breast and other cancers between pregnant women with and without diabetes. MethodsThis work was a propensity-matched, retrospective cohort study using population-based health-care databases from Ontario, Canada. Those deliveries with gestational diabetes mellitus (GDM) and pregestational diabetes mellitus (pregestational DM) were identified and matched to deliveries without diabetes mellitus (non-DM). Deliveries from each diabetes cohort were matched 1:2 on age, parity, year of delivery, and propensity score to non-DM deliveries. Matched subjects were followed from delivery for incidence of breast cancer as a primary outcome, and other site-specific cancers as secondary outcomes. We performed Cox proportional hazards regression to compare rates of breast cancer between matched groups. ResultsOver a median of 8 (interquartile range 4 to 13) years of follow-up, compared with non-DM deliveries, the incidence of breast cancer was significantly lower for GDM but similar for pregestational DM deliveries (hazard ratio [HR] 0.90, 95% confidence interval [CI] 0.82 to 0.98; and HR 0.92, 95% CI 0.80 to 1.07, respectively). GDM was associated with a significantly higher incidence of pancreatic and hepatocellular cancer, and pregestational DM was associated with a higher incidence of thyroid, hepatocellular, and endometrial cancers. ConclusionsDiabetes in pregnancy does not have a higher short-term risk of subsequent breast cancer, but there may be a higher incidence of other cancers.

Management of Endometrial Intraepithelial Neoplasia or Atypical Endometrial Hyperplasia

(Abstracted from Obstet Gynecol 2023;142(3)) Endometrial cancer incidence is rising in the United States and disproportionally affects patients based on race, geography, and socioeconomic status. Endometrial intraepithelial neoplasia (EIN) or atypical endometrial hyperplasia (AEH) is often precursor lesions to adenocarcinoma in the endometrium.

Abstract A061: Understanding health-seeking delays for post-menopausal bleeding among Haitian women

Abstract Introduction: Black women have the highest risk of Endometrial cancer (EC) among any racial group in the US. When disaggregated, Haitian women specifically have been shown to have a higher incidence of high-grade EC, present at more advanced stages, and have lower overall survival compared to US-born Blacks. There is no screening test for EC, and women are diagnosed when they develop symptoms. The most common symptom of EC is postmenopausal bleeding (PMB). Little data exist about understanding/perception of PMB and subsequent care-seeking delays in this population of at-risk women. Utilizing the Safer and Anderson model of total patient delay, our objective was to qualitatively evaluate perceptions of PMB and how these may guide care-seeking behaviors among a healthy population of at-risk postmenopausal Haitian women. Methods: Nineteen women were included. Participants were 1) Haitian Black women; 2) ≥ 50 years of age; 3) living in South Florida; and 4) without a personal or family history of breast or gynecologic cancer. Participants were recruited through a mix of purposive and snowball sampling strategies via multiple channels (community outreach, radio advertisements, social media). Women participated in focus group discussions, conducted in Creole, and guided by a semi-structured interview guide designed to capture perceptions about PMB. Sessions were audio recorded, transcribed, and coded by a team of 5 raters. Dedoose software was used for content analyses and identification of emerging themes. Results: Three key themes that aligned primarily within the Safer and Andersen constructs of appraisal delay and illness delays were identified: 1) There was a significant lack of knowledge about the meaning of PMB. Resumption of fertility, PMB as a normal part of aging, and interpreting the symptom as reflective of a benign disease (e.g., food poisoning) were common. Cancer was not a primary concern in the setting of PMB, and there was consistent low perceived severity of the symptom. In fact, there was a conveyed sense of invulnerability to cancer purely due to the nature of being Haitian. 2) Women would preferentially use cultural-specific coping strategies in lieu of seeking immediate medical care. Such strategies included use of home remedies such as teas, and prayer/reliance on God. 3) Appraisal of PMB and discussion of severity involves consultation with spiritual leaders and others in the community for guidance. There was a perception that community members may dissuade the pursuit of traditional medical care. The use of the Internet as a facilitator for care was not considered primary. Conclusion: This study underscores the complexity of factors impacting potential help-seeking delays among Haitian women experiencing PMB. Our findings highlight the need for culturally-tailored, comprehensive educational interventions to increase awareness of the meaning of PMB and its health relevance to improve earlier care-seeking and timely diagnosis of EC. Citation Format: Maurice J. Chery, Vanessa Morales, Lashae Rolle, Alejandra Casas, Diana Zapata, Sophia H.L. George, Matthew P. Schlumbrecht. Understanding health-seeking delays for post-menopausal bleeding among Haitian women [abstract]. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr A061.

Elevated preoperative hemoglobin A1c is associated with higher stage and grade of endometrial carcinoma

Introduction: The incidence of endometrial cancer (EC) and diabetes mellitus has been linked in many studies. EC patients had more severely impaired glucose tolerance than individuals with other malignancies. An indicator that determines glycemic index control is hemoglobin A1c (HbA1c). This study aimed to assess whether the preoperative level of HbA1c in diabetes mellitus patients is related to the stage and grade of endometrial carcinoma. Methods: This cross-sectional study uses a retrospective observational analytic design. Diabetes mellitus patients diagnosed with EC and measured for HbA1c levels in Dr. Kariadi General Hospital Semarang from January 2018 to December 2021 were involved as the subjects of this study. The data was analyzed using correlation analysis and linear regression analysis. A value of p&lt;0.05 was used to determine the statistical significance. Results: This study involved 27 EC patients who had preoperative HbA1c data. The overall average HbA1c was 7.88±1.35 in the early-stage group and 10.85±1.15 in the advanced-stage group, significantly different between groups (p&lt;0.001). There was also a significant difference between HbA1c in low-grade and high-grade tumors (p&lt;0.001). With an increase of HbA1c in one unit value, the endometrial carcinoma stage also increases by 0.323 units or 32.3%, while the grade of endometrial carcinoma also increases by 0.275 units or 27.5%. Conclusion: HbA1c level significantly correlates with both the stage and grade of EC. This study also found a linear relationship between increased HbA1c levels and higher stage and grade of EC, indicating that HbA1c levels influence the stage and grade of endometrial carcinoma.

Global and regional trends in the incidence and mortality burden of endometrial cancer, 1990-2019: Updated results from the Global Burden of Disease Study, 2019.

The disease burdens for endometrial cancer (EC) vary across different countries and geographical regions and change every year. Herein, we reported the updated results of the Global Burden of Disease Study 2019 on EC with respect to age-standardized incidence and mortality from 1990 to 2019. The annual percentage change (APC) of incidence and mortality was evaluated using joinpoint regression analysis to examine the temporal trends during the same timeframe in terms of the global landscape, different sociodemographic indices (SDI), and geographic regions. The relationship between Human Development Index (HDI) and incidence and mortality was additionally explored. The age-standardized incidence rates (ASIRs) revealed a significant average global elevation by 0.5% per year (95% confidence interval [CI], 0.3-0.7; P <0.001). The age-standardized mortality rates (ASMRs), in contrast, fell by an average of 0.8% per year (95% CI, -1.0 to -0.7; P <0.001) worldwide. The ASIRs and ASMRs for EC varied across different SDIs and geographical regions. We noted four temporal trends and a significant reduction by 0.5% per year since 2010 in the ASIR, whereas we detected six consecutively decreasing temporal trends in ASMR during the entire period. Notably, the estimated APCs were significantly positively correlated with HDIs (ρ = 0.22; 95% CI, 0.07-0.35; P = 0.003) with regard to incident cases in 2019. Incidence rates for EC reflected a significant increase overall (although we observed a decline since 2010), and the death rates declined consecutively from 1990 to 2019. We posit that more precise strategies can be tailored and then implemented based on the distinct age-standardized incidence and mortality burden in different geographical areas.

Increasing incidence of endometrial cancer in Aotearoa New Zealand: Health professionals' perspective.

The incidence of endometrial cancer is globally increasing. Aotearoa New Zealand is no exception with a 59% increase in cases over that last ten years. We report a sub-set of themes which pertain to provider reflections of rising endometrioid-type endometrial cancer incidence in individuals with high weight. Fifteen semi-structured interviews with healthcare professionals experienced in providing care to women with endometrial cancer were audio-recorded and transcribed. Interviews were analysed using reflexive thematic analysis. Two main themes emerged: (1) concerns for the future; and (2) impact on fertility and treatment options. Healthcare professionals discussed rising incidence in younger people and a need for increased awareness about the association of excess weight as a risk factor for developing the disease. The concern extended to workforce and equipment shortfalls of meeting the needs of individuals with higher weight, which subsequently influenced treatment options, health outcomes and survivorship. Rising incidence of endometrial cancer in individuals with high weight presents multiple chances for inequitable access and health outcomes over the care continuum for endometrial cancer. Action is required to address incidence, awareness, access to equitable and inclusive treatment, and survivorship.