endometrial cancer thesis

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• Published: 09 December 2021
• Endometrial cancer
• Vicky Makker   ORCID: orcid.org/0000-0001-9793-7614 1 , 2 ,
• Helen MacKay 3 ,
• Isabelle Ray-Coquard   ORCID: orcid.org/0000-0003-2472-8306 4 ,
• Douglas A. Levine 5 , 6 ,
• Shannon N. Westin   ORCID: orcid.org/0000-0002-1922-0156 7 ,
• Daisuke Aoki 8 &
• Ana Oaknin   ORCID: orcid.org/0000-0002-3592-7194 9  

Nature Reviews Disease Primers volume  7 , Article number:  88 ( 2021 ) Cite this article

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• Cancer microenvironment

Although endometrial cancer management remains challenging, a deeper understanding of the genetic diversity as well as the drivers of the various pathogenic states of this disease has led to development of divergent management approaches in an effort to improve therapeutic precision in this complex malignancy. This comprehensive review provides an update on the epidemiology, pathophysiology, diagnosis and molecular classification, recent advancements in disease management, as well as important patient quality-of-life considerations and emerging developments in the rapidly evolving therapeutic landscape of endometrial cancers.

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Acknowledgements

V.M. is supported in part through the NIH/NCI Cancer Center Support Grant P30 CA008748. S.N.W. is supported in part through the NIH/NCI Cancer Center Support Grant (NIH CA016672) and the NIH SPORE in Uterine Cancer (NIH 5P50CA098258-13).

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Vicky Makker

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Helen MacKay

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Introduction (V.M.); Epidemiology (V.M.); Mechanisms/pathophysiology (I.R.-C. and D.A.L.); Diagnosis, screening and prevention (A.O.); Management (H.M.); Quality of life (D.A.); Outlook (S.N.W.); Overview of Primer (V.M.).

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Outside the submitted work, V.M. reports research (all funding to institution)/consultant/advisory board member support from Merck, Eisai, Karyopharm, AstraZeneca, Clovis, Moreo, Takeda, Zymeworks, Genentech, GSK, Dicephera and Faeth. D.A.L. has held consulting/advisory role for Tesaro/GSK, Merck, receives research funding to his institution from Merck, Tesaro, Clovis Oncology, Regeneron, Agenus, Takeda, Immunogen, VBL Therapeutics, Genentech, Celsion, Ambry and Splash Pharmaceuticals. D.A.L. is a founder of Nirova BioSense, Inc. D.A.L. is currently a full-time employee of Merck. I.R.-C. reports honoraria (self) from AbbVie, Agenus, Advaxis, BMS, PharmaMar, Genmab, Pfizer, AstraZeneca, Roche, GSK, MSD, Deciphera, Mersena, Merck Sereno, Novartis, Amgen, Tesaro and Clovis; honoraria (institution) from GSK, MSD, Roche and BMS; advisory/consulting fees from AbbVie, Agenus, Advaxis, BMS, PharmaMar, Genmab, Pfizer, AstraZeneca, Roche/Genentech, GSK, MSD, Deciphera, Mersena, Merck Sereno, Novartis, Amgen, Tesaro and Clovis; research grant/funding (self) from MSD, Roche and BMS; research grant/funding (institution) from MSD, Roche, BMS, Novartis, AstraZeneca and Merck Sereno; and travel support from Roche, AstraZeneca and GSK. A.O. has served on advisory boards for Roche, AstraZeneca, PharmaMar, Clovis Oncology, Tesaro, Inmunogen, Genmab, Mersana Therapeutic, GSK and Deciphera Pharmaceutical and has received support for travel or accommodation from Roche, AstraZeneca and PharmaMar. H.M. has served on the advisory boards of Merck, Essai, GSK and AstraZeneca. D.A. has research grant support from Aska Pharmaceutical, Takeda and Tsumura; has served as consultant for AstraZeneca, Takeda, MSD, Myriad Genetics, AbbVie, Chugai and Ono; and has received honoraria from AbbVie, MSD, Aska Pharmaceutical, AstraZeneca, Takeda, Chugai, Ono, Taiho and Bayer. S.N.W. reports research support from ArQule, AstraZeneca, Bayer, Bio-Path, Clovis Oncology, Cotinga Pharmaceuticals, GSK/Tesaro, Mereo, Novartis, Roche/Genentech and Zentalis; and has served as consultant for Agenus, AstraZeneca, Circulogene, Clovis Oncology, Eisai, EQRX, GSK/Tesaro, Lilly, Merck, Novartis, Pfizer, Roche/Genentech and Zentalis.

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Makker, V., MacKay, H., Ray-Coquard, I. et al. Endometrial cancer. Nat Rev Dis Primers 7 , 88 (2021). https://doi.org/10.1038/s41572-021-00324-8

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• Introduction
• Conclusions
• Article Information

The pooled prevalence of PMB is indicated by the dotted line. ES indicates effect size; LR, likelihood ratio; and diamond, pooled risk.

The pooled risk of endometrial cancer in all 92 studies is indicated by the dotted line. ES indicates effect size.

Figure 3 is a continuation of Figure 2. The pooled risk of endometrial cancer in all 92 studies is indicated by the dotted line. ES indicates effect size; LR, likelihood ratio; and diamond, pooled risk.

The pooled risk of endometrial cancer in all 92 studies is indicated by the dotted line. ES indicates effect size; HT, hormone therapy; LR, likelihood ratio; and diamond, pooled risk.

eFigure 1. PRISMA Flow Diagram

eFigure 2. Prevalence of PMB in Women With Stage I vs Stages II-IV Endometrial Cancers

eFigure 3. Prevalence of PMB in Women With Endometrial Cancer, Stratified by Geographic Region

eFigure 4. Prevalence of PMB in Women With Endometrial Cancer by Study Enrollment Period

eFigure 5. Risk of Endometrial Cancer in Women With PMB by Geographic Region

eFigure 6. Risk of Endometrial Cancer in Women With PMB, Stratified by Study Enrollment Period

eFigure 7. Risk of Endometrial Cancer in Women With PMB by Potential for Study Verification Bias

eFigure 8. Risk of Endometrial Cancer in Women With Postmenopausal Bleeding (PMB) by Hormone Therapy Selection Criteria

eMethods. Study Retrieval and Evaluation and Data Analysis

eTable 1. Results of Quality Assessment of the 92 Studies Included in the Analysis of Risk of Endometrial Cancer in Women With PMB

eTable 2. Results of Sensitivity Analyses Based on Quality Assessment

• Opportunities for Early Detection of Endometrial Cancer in Women With Postmenopausal Bleeding JAMA Internal Medicine Invited Commentary September 1, 2018 Kristen A. Matteson, MD, MPH; Katina Robison, MD; Vanessa L. Jacoby, MD, MAS

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Although only 10% of post-menopausal bleeding is associated with endometrial cancer, the remainder of the cases that are benign or hyperplasia allow for education around the future risks for endometrial cancer and can contribute to lifestyle change when  weight, centripetal obesity, hypertension and diabetes are addressed. When patients are concerned about "cancer" they tend to be more motivated.

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Clarke MA , Long BJ , Del Mar Morillo A , Arbyn M , Bakkum-Gamez JN , Wentzensen N. Association of Endometrial Cancer Risk With Postmenopausal Bleeding in Women : A Systematic Review and Meta-analysis . JAMA Intern Med. 2018;178(9):1210–1222. doi:10.1001/jamainternmed.2018.2820

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Association of Endometrial Cancer Risk With Postmenopausal Bleeding in Women : A Systematic Review and Meta-analysis

• 1 Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, Maryland
• 2 Department of Obstetrics and Gynecology, Mayo Clinic, Rochester, Minnesota
• 3 Unit of Cancer Epidemiology, Belgian Cancer Centre, Sciensano, Brussels, Belgium
• Invited Commentary Opportunities for Early Detection of Endometrial Cancer in Women With Postmenopausal Bleeding Kristen A. Matteson, MD, MPH; Katina Robison, MD; Vanessa L. Jacoby, MD, MAS JAMA Internal Medicine

Question   What is the prevalence of postmenopausal bleeding in women with endometrial cancer and the risk of endometrial cancer in women with postmenopausal bleeding?

Findings   This systematic review and meta-analysis of 40 790 unique patients in 129 unique studies suggests that postmenopausal bleeding occurs in approximately 90% of women with endometrial cancer; however, only 9% of women with postmenopausal bleeding were diagnosed with endometrial cancer. These estimates varied by geographic region, hormone use, and calendar time.

Meaning   These findings provide a foundation for evaluating early detection strategies for endometrial cancer and can support risk-informed decision making in clinical management of postmenopausal bleeding.

Importance   As the worldwide burden of endometrial cancer continues to rise, interest is growing in the evaluation of early detection and prevention strategies among women at increased risk. Focusing efforts on women with postmenopausal bleeding (PMB), a common symptom of endometrial cancer, may be a useful strategy; however, PMB is not specific for endometrial cancer and is often caused by benign conditions.

Objective   To provide a reference of the prevalence of PMB in endometrial cancers and the risk of endometrial cancer in women with PMB.

Data Sources   For this systematic review and meta-analysis, PubMed and Embase were searched for English-language studies published January 1, 1977, through January 31, 2017.

Study Selection   Observational studies reporting the prevalence of PMB in women with endometrial cancer and the risk of endometrial cancer in women with PMB in unselected populations were selected.

Data Extraction and Synthesis   Two independent reviewers evaluated study quality and risk of bias using items from the Newcastle-Ottawa Quality Assessment Scale and the Quality Assessment of Diagnostic Accuracy Studies tool. Studies that included highly selected populations, lacked detailed inclusion criteria, and/or included 25 or fewer women were excluded.

Main Outcomes and Measures   The pooled prevalence of PMB in women with endometrial cancer and the risk of endometrial cancer in women with PMB.

Results   A total of 129 unique studies, including 34 432 unique patients with PMB and 6358 with endometrial cancer (40 790 women), were analyzed. The pooled prevalence of PMB among women with endometrial cancer was 91% (95% CI, 87%-93%), irrespective of tumor stage. The pooled risk of endometrial cancer among women with PMB was 9% (95% CI, 8%-11%), with estimates varying by use of hormone therapy (range, 7% [95% CI, 6%-9%] to 12% [95% CI, 9%-15%]; P  < .001 for heterogeneity) and geographic region (range, 5% [95% CI, 3%-11%] in North America to 13% [95% CI, 9%-19%] in Western Europe; P  = .09 for heterogeneity).

Conclusions and Relevance   Early detection strategies focused on women with PMB have the potential to capture as many as 90% of endometrial cancers; however, most women with PMB will not be diagnosed with endometrial cancer. These results can aid in the assessment of the potential clinical value of new early detection markers and clinical management strategies for endometrial cancer and will help to inform clinical and epidemiologic risk prediction models to support decision making.

Endometrial cancer is the most common gynecologic cancer in developed countries and accounts for nearly 5% of cancer cases and more than 2% of deaths due to cancer in women worldwide. 1 In regions such as North America and parts of Europe, the incidence of endometrial cancer is disproportionately higher than in other developed countries, which may be attributed to higher rates of obesity, as well as other important risk factors such as aging, early menarche, late menopause, nulliparity, and postmenopausal estrogen therapy use. 2 Unlike most cancers, the incidence of endometrial cancer and associated mortality rates have increased in recent years 3 - 7 and are projected to rise during the next 10 years. 8 - 11

Most endometrial cancers are diagnosed at a localized stage and are often curable with surgery, with a 5-year survival of approximately 95%. In contrast, 5-year survival for late-stage (stage IV) endometrial cancer ranges from 16% to 45%. 12 - 14 However, studies evaluating early detection strategies for endometrial cancer are lacking, and at present no recommendation for population-based screening exists. In the era of precision prevention, emphasis on identifying individuals at high risk to maximize the positive outcomes of clinical interventions while avoiding unnecessary harms is growing. 15 - 17 Rather than targeting the whole population, early detection strategies for endometrial cancer could focus on women at high risk of developing endometrial cancer, while excluding most women at low risk. Postmenopausal bleeding (PMB) is a common symptom of endometrial cancer and accounts for approximately two-thirds of all gynecologic visits among perimenopausal and postmenopausal women. 18 Women presenting with PMB undergo additional clinical testing using a combination of transvaginal ultrasonography (TVUS), hysteroscopy, endometrial biopsy, and/or dilation and curettage, and workup varies widely among different settings. 18 - 20 However, PMB is often associated with benign conditions such as endometrial polyps or may result from unscheduled bleeding in women using hormone therapy (HT). 18 , 21 The risk of endometrial cancer in women with PMB varies widely in individual studies from 3% to 25%. 22 - 27

Accurate estimates of the prevalence of PMB in endometrial cancers (equal to the sensitivity of PMB for detecting endometrial cancer) and the risk of endometrial cancer in women with PMB (equal to the positive predictive value [PPV] of PMB for detecting endometrial cancer) are needed to evaluate whether targeting women with PMB for early detection is a useful strategy, particularly because endometrial cancer rates are increasing in the population. A high sensitivity of PMB would ensure that most cases of endometrial cancer are being captured by targeting this population. A high PPV of PMB, which translates into a low number needed to diagnose (1/PPV) to find 1 case of endometrial cancer, would support diagnostic workup of women with PMB, whereas a low PPV would signify the need for additional triage to improve performance of early detection. Furthermore, these estimates would provide the foundation for evaluating clinical and epidemiologic risk prediction models 28 and are necessary for evaluating novel molecular markers that are currently under development against established methods. 29 - 33

We conducted a systematic review and meta-analysis to evaluate the prevalence of PMB in women with endometrial cancer and the risk of endometrial cancer among women with PMB. Our estimates could inform the evaluation of clinical scenarios to assess the utility of early detection strategies for endometrial cancer.

We conducted this systematic review and meta-analysis following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines (eFigure 1 in the Supplement ). 34 We included original studies with primary data reporting the prevalence of PMB in women with endometrial cancer and the risk of endometrial cancer among women with PMB. We searched English-language, peer-reviewed studies published before February 1, 2017, in the MEDLINE database via PubMed and Embase using search terms described in eMethods in the Supplement . We also reviewed the reference lists of articles identified in the primary search for additional relevant studies. Titles and abstracts were independently screened for inclusion by 3 investigators (M.A.C., A.D.M., and B.J.L.). Full-text versions of eligible articles were reviewed by 2 investigators (M.A.C. and B.J.L.) to determine eligibility; any questions regarding the inclusion of studies were resolved by the senior author (N.W.). We evaluated data on patient selection criteria, sample size, and exposure and outcome ascertainment to determine study quality and generalizability; we excluded studies that included special populations (eg, defined by comorbid conditions or specific histologic findings), lacked detailed inclusion criteria, and/or included 25 or fewer women.

We extracted information on aggregate study-level participant characteristics (age, body mass index, years since menopause, parity, frequency of bleeding, HT use, tamoxifen use, and other comorbidities) and endometrial biopsy results, including stage and histologic data when available. Geographic regions were defined by the World Health Organization for those with 2 or more countries represented. 1 Study designs were classified as retrospective or prospective if follow-up time was specified or as cross-sectional (or case series). We assessed study quality using items from the Newcastle-Ottawa Quality Assessment Scale 35 and the Quality Assessment of Diagnostic Accuracy Studies tool 36 (eMethods in the Supplement ). We provide the detailed algorithms of how PMB was evaluated for each study in eTable 1 in the Supplement . Studies were classified as having potential verification bias if receipt or interpretation of the diagnostic test (eg, endometrial biopsy) depended on the results of a prior clinical test (eg, TVUS) (eMethods in the Supplement ).

We estimated pooled prevalence and 95% CIs using multilevel logistic-normal random-effects models to account for interstudy heterogeneity. Between-study variance was quantified using the τ 2 statistic. 37 , 38 We visualized variation in study-specific estimates using forest plots and performed subgroup analyses (described in eMethods in the Supplement ) to evaluate the influence of (1) study exclusion criteria for HT use (analysis of risk of endometrial cancer in women with PMB only); (2) geographical region; and (3) study enrollment period, using the last year of study enrollment or publication date as a proxy, grouped as before 1990, 1990 to 1999, 2000 to 2009, and 2010 to 2017. We use the P value for heterogeneity to compare subgroup estimates, with significance at P  < .05. The influence of continuous study-level (mean) characteristics, including age, years since menopause, and percentage using HT, was explored using multilevel logistic random-effects models for studies with available data. We conducted sensitivity analyses to assess the influence of clinical setting (tertiary center vs other), study design, and the potential for publication bias using Egger regression analyses. 29 For the analysis of the prevalence of PMB in women with endometrial cancer, we excluded 2 studies 39 , 40 that selected cases based on stage at diagnosis; however, these studies were included in the stage-specific analysis. For the analysis of the risk of endometrial cancer among women with PMB, we conducted a secondary analysis in a subset of 10 studies 41 - 50 that excluded women with measurements below a minimum endometrial thickness determined by TVUS (range, 4-5 mm) and a separate subset of 7 studies 51 - 57 that evaluated the risk of endometrial cancer in women with polyps.

As an ancillary analysis, we simulated the performance of 2 approaches for early detection of endometrial cancer in a hypothetical population of 10 000 women with PMB to demonstrate how our results can be used to evaluate current testing strategies and the potential clinical value of early-stage biomarkers for endometrial cancer detection: TVUS (cutoff of ≤3 mm), which is a well-established, clinically validated test, 18 and an experimental methylation marker assay 31 , 32 (eMethods in the Supplement ). All analyses were performed in Stata, version 13 (StataCorp). For pooling of proportions, we used the program metaprop_one. 38

We identified 2398 studies, of which 129 were eligible for our analysis, 22 - 27 , 39 - 162 with 40 790 unique patients, including 1 study 58 that was eligible for both analyses (overlap of 45 women with endometrial cancers and 45 women with PMB) (eFigure 1 in the Supplement ). Studies were published from January 1, 1977, through January 1, 2017, and most were cross-sectional and conducted in Northern (26 [20.2%]) and Southern Europe (24 [18.6%]). Among eligible studies, 21 39 , 40 , 58 - 72 , 74 - 77 were included for analysis of the prevalence of PMB in women with endometrial cancer (3792 cases of endometrial cancer, of which 3257 were in women with PMB, including the 2 studies restricted to stages III-IV cancers 39 , 40 ) and 92 22 - 27 , 58 , 78 - 162 were included for analysis of the risk of endometrial cancer in women with PMB (31 220 women with PMB and 2611 cases of endometrial cancer).

Study-specific and pooled estimates of the prevalence of PMB in women with endometrial cancer are shown in Figure 1 . The prevalence of PMB was 90% (95% CI, 84%-94%), with substantial between-study variance (τ 2  = 1.14). Removal of a potential outlier 74 resulted in a similar pooled prevalence of 91% (95% CI, 87%-93%), but strong reduction of variance between studies (τ 2  = 0.47); therefore we excluded the outlier study from the remaining analyses. Among 5 studies 66 , 70 , 72 , 75 , 76 with information on stage I tumors, the proportion of PMB was 94% (95% CI, 72%-99%; τ 2  = 4.03). Among the 7 studies 39 , 40 , 66 , 70 , 72 , 75 , 76 with information on stages II to IV tumors, the proportion of PMB was 84% (95% CI, 71%-92%; τ 2  = 0.93). We found no significant difference in prevalence of PMB by stage ( P  = .20 for heterogeneity) (eFigure 2 in the Supplement ).

In an analysis stratified by geographic region, the prevalence of PMB ranged from 94% (95% CI, 84%-97%) in North America to 90% in Western Asia (95% CI, 85%-94%) and Eastern Asia (95% CI, 83%-94%) ( P  = .55 for heterogeneity) (eFigure 3 in the Supplement ). The pooled prevalence of PMB among women with endometrial cancer varied significantly by study enrollment period ( P  < .001 for heterogeneity). The prevalence of PMB in women with endometrial cancer was higher in studies that enrolled women before 1990 (94%; 95% CI, 92%-95%) and in 1990 to 1999 (96%; 95% CI, 87%-99%) compared with studies that enrolled women in 2000 to 2009 (85%; 95% CI, 78%-90%) and in 2010 to 2017 (86%; 95% CI, 82%-90%) (eFigure 4 in the Supplement ).

In a sensitivity analysis restricted to 11 studies 59 , 62 , 64 , 66 - 68 , 70 - 72 , 75 , 76 (67%) that ascertained PMB through retrospective medical record review, the pooled prevalence of PMB was 91% (95% CI, 85%-94%), similar to our overall findings. The prevalence of PMB did not vary significantly by clinical setting. No evidence of publication bias was found among studies reporting the prevalence of PMB in women with endometrial cancer (Egger regression intercept, 0.15; P  = .90).

Study-specific and pooled estimates of the risk of endometrial cancer in women with PMB are shown in Figures 2 and 3 . In 92 studies, 22 - 27 , 58 , 78 - 162 the risk of endometrial cancer ranged from 0% to 48%, yielding an overall pooled estimate of 9% (95% CI, 8%-11%), with moderate variability observed between studies (τ 2  = 0.56).

The pooled risk of endometrial cancer was significantly higher among the 41 studies 22 , 24 , 58 , 82 , 89 , 92 - 94 , 98 , 99 , 101 - 106 , 112 , 115 , 116 , 118 , 120 , 121 , 127 , 133 , 136 - 138 , 140 , 141 , 143 - 147 , 149 , 150 , 152 , 158 , 160 - 162 that excluded women using HT (12%; 95% CI, 9%-15%; τ 2  = 0.64) ( Figure 4 ) compared with the 51 studies that included women using HT 21 , 23 , 25 - 27 , 78 - 81 , 83 - 88 , 90 , 91 , 95 - 97 , 100 , 107 - 111 , 113 , 114 , 117 , 119 , 122 - 126 , 128 - 131 , 134 , 135 , 139 , 142 , 148 , 151 , 153 - 157 , 159 (7%; 95% CI, 6%-9%; τ 2  = 0.38; P  < .001 for heterogeneity) (eFigure 8 in the Supplement ).

The risk of endometrial cancer in women with PMB was lowest in North America (5%; 95% CI, 3%-11%; τ 2  = 0.78) and Northern Europe (7%; 95% CI, 5%-8%; τ 2  = 0.24) and highest in Western Europe (13%; 95% CI, 9%-19%; τ 2  = 0.61) ( P  = .09 for heterogeneity) (eFigure 5 in the Supplement ). In an analysis restricted to European countries only, the risk of endometrial cancer was significantly higher in Western Europe compared with Northern and Southern Europe ( P  = .03 for heterogeneity). After stratifying by exclusion of women who used HT, significant regional differences persisted in both strata ( P  = .02 for heterogeneity in studies that included women using HT; P  < .001 for heterogeneity in studies that excluded women using HT).

The risk of endometrial cancer was significantly higher in studies with enrollment periods before 1990 (13%; 95% CI, 10%-17%; τ 2  = 0.18) and in 1990 to 1999 (11%; 95% CI, 8%-13%; τ 2  = 0.57) compared with 2000 to 2009 (7%; 95% CI, 5%-9%; τ 2  = 0.47) and 2010 to 2017 (8%; 95% CI, 5%-12%; τ 2  = 0.59) ( P  < .001 for heterogeneity) (eFigure 6 in the Supplement ). The risk of endometrial cancer was not significantly associated with mean age, number of years since menopause, and percentage of women using HT.

The risk of endometrial cancer was significantly lower in prospective 22 , 26 , 27 , 58 , 88 , 105 , 122 - 124 , 135 , 138 - 140 , 150 (6%; τ 2  = 0.34) and retrospective 23 , 25 , 83 , 94 , 97 , 113 , 125 , 131 , 134 , 147 , 148 , 151 , 153 , 155 , 158 , 161 (6%; τ 2  = 0.37) studies compared with cross-sectional studies 78 - 82 , 84 - 87 , 90 - 93 , 95 , 96 , 98 - 104 , 106 - 112 , 114 - 121 , 126 - 130 , 132 , 133 , 136 , 137 , 141 - 146 , 149 , 152 , 154 , 156 , 157 , 159 , 160 , 162 (11%; τ 2  = 0.49; P  < .001 for heterogeneity) and was significantly higher in 6 studies 24 , 110 , 121 , 130 , 152 , 157 conducted in tertiary centers (23%; 95% CI, 17%-31%; τ 2  = 0.18; P  < .001 for heterogeneity), compared with studies conducted in other settings. Evidence of publication bias suggested that small studies may overestimate the risk of endometrial cancer in women with PMB (Egger regression intercept, 0.75; P  = .001). In an analysis based on the assessment of study quality, verification bias could be excluded in 71 studies 24 - 26 , 58 , 78 , 79 , 81 - 96 , 98 - 106 , 108 , 110 - 115 , 117 - 122 , 125 , 126 , 128 , 130 - 133 , 135 - 137 , 139 - 141 , 143 - 147 , 149 , 150 , 152 , 154 , 156 - 158 , 161 , 162 and was potentially present in 13 studies 22 , 27 , 107 , 109 , 123 , 124 , 127 , 129 , 138 , 142 , 148 , 155 , 159 (8 were unclear). The risk of endometrial cancer was significantly lower in studies with potential verification bias (6%; 95% CI, 4%-9%) compared with those with no verification bias (10%; 95% CI, 8%-12%) (eTable 2 and eFigure 7 in the Supplement ).

In the 10 studies 41 - 50 that included women with PMB and a minimum endometrial thickness (n = 2087), the pooled risk of endometrial cancer was 19% (95% CI, 14%-25%; τ 2  = 0.28). In 7 studies 51 - 57 restricted to women with PMB and polyps (n = 2801), the pooled risk of endometrial cancer was 3% (95% CI, 3%-4%; τ 2  = 0).

To demonstrate how the estimates from this meta-analysis can be used to evaluate strategies for endometrial cancer detection in women with PMB, we evaluated the performance of TVUS, a well-established clinical test for evaluating PMB 18 and an experimental methylation assay for endometrial cancer detection 31 , 32 in a hypothetical population of 10 000 women with PMB. We evaluated endometrial cancer risk estimates of 5%, 10%, and 15%, representing the range of risks observed in different geographic regions ( Table ). We show the magnitude of the increase in PPV of both tests with increasing risk of endometrial cancer in women with PMB, supporting the evaluation of early-detection strategies in various populations.

The projected rise in endometrial cancer incidence and mortality underscores the importance of strategies for early detection and prevention. Focusing on women at highest risk of endometrial cancer can greatly improve the performance of a diagnostic test and avoid unnecessary testing and associated harms among women at low risk. Our systematic review and meta-analysis demonstrates that PMB is very sensitive for endometrial cancer detection, occurring in approximately 90% of cases. However, our findings indicate that among women with PMB, only approximately 9% will be diagnosed with endometrial cancer, with estimates varying substantially by HT use, geographic region, and the presence of endometrial polyps. Current practice guidelines recommend workup to rule out endometrial cancer among all women with PMB. Our findings support this recommendation by providing reassurance that targeting this high-risk group of women for early detection and prevention strategies will capture most endometrial cancers. However, the low PPV of PMB emphasizes the need for additional triage tests with high specificity to improve management of PMB and avoid unnecessary biopsies in low-risk women.

The prevalence of PMB in endometrial cancer and the risk of endometrial cancer in women with PMB were higher before 2000 compared with after 2000. When interpreting these results, it is important to distinguish population risk, which has generally increased over time, from the risk in women with PMB. The number of endometrial cancers without PMB and the number of women with PMB with benign conditions may both have increased over time. This increase could be influenced by factors such as changes in HT use, changes in prevalence of obesity, or changes in clinical management thresholds for abnormal bleeding.

The risk of endometrial cancer among women with PMB was notably lower in studies that included HT users compared with those that excluded these women. Use of HT may affect this association at multiple levels. Certain combined formulations of estrogen plus progestin therapy are established to have a protective effect on the endometrium. 163 Furthermore, irregular uterine bleeding is a common adverse effect of HT, particularly within the first 6 months of use. 164 The underlying causes of HT-induced bleeding is thought to involve changes in the size of endometrial blood vessels and regulation of vascular growth and integrity. 165 Because this type of bleeding is generally not associated with abnormal endometrial histologic findings, most guidelines recommend against clinical workup of women using HT who experience irregular uterine bleeding within the first 6 months. However, little consensus exists about how to best treat these women if bleeding persists, and a considerable number of women with HT-associated bleeding will undergo procedures to rule out endometrial cancer. 165 Our data emphasize the importance of considering a woman’s HT status to inform clinical decision making, potentially supporting a less aggressive management approach in HT users.

We noted striking geographic differences in endometrial cancer risk among women with PMB, ranging from 13% in Western Europe to 5% in North America and 7% in Northern Europe. At present, consensus regarding the optimal approach for evaluating PMB is lacking. Practice may vary depending on resources, clinical expertise and judgment, and patient preferences. The threshold for evaluating PMB may be lower in North American countries compared with other countries in Europe and elsewhere. In many European countries, guidelines recommend TVUS as the first-line test, with histologic assessment indicated for women with a thickened endometrium based on cutoffs ranging from 3 to 5 mm. 18 , 166 , 167 In the United States, guidelines recommend TVUS or endometrial biopsy as the first step in evaluating PMB. 19 In sensitivity analyses, we observed a lower risk of endometrial cancer in studies with partial disease verification (ie, not all women received a biopsy) compared with studies with complete diagnostic verification, suggesting that disease may have been missed in women with negative findings for the first-line test (eg, TVUS). However, we cannot exclude that in some settings, women only received a first-line test such as TVUS if they had a lower risk of endometrial cancer. In the subset of studies included in our meta-analysis that included women with PMB and a minimum endometrial thickness, the pooled risk of endometrial cancer was 19%, more than double the risk observed in our main analysis.

Our findings also suggest substantial variation in the risk of endometrial cancer depending on the underlying cause of PMB. Endometrial polyps are one of the most common causes of PMB. Although polyps have been associated with risk of endometrial cancer in women with PMB, 168 other studies have suggested that this association is more likely attributed to detection bias, resulting from incidental findings during the diagnostic workup of PMB caused by endometrial polyps. 169 Our meta-analysis confirms a lower risk of endometrial cancer among women with PMB and polyps.

To our knowledge, this systematic review and meta-analysis is the first to evaluate the prevalence of PMB in endometrial cancer and the risk of endometrial cancer in women with PMB, 2 important variables for evaluating the role of PMB in early detection of endometrial cancer. Our findings can support risk-informed decision making in clinical management of women with PMB. As an example, we simulated the performance of TVUS, an established diagnostic tool, and methylation markers, an early-phase biomarker, for early detection of endometrial cancer. We provided estimates of how many women would be referred for endometrial biopsy for combinations of endometrial cancer risk in women with PMB, and we showed how many women would need to undergo endometrial biopsy to identify 1 case.

However, a few study limitations are worth noting. In general, data on study-level variables such as years since menopause and body mass index were inconsistently reported, limiting our ability to evaluate them. In addition, insufficient data were available to explore differences by histologic findings, stage, and grade. Whether cancers with more favorable histologic findings (eg, endometrioid type I tumors) are more likely to present with PMB compared with more aggressive histologic subtypes (eg, serous type II tumors) remains unknown. Our results suggest that approximately 10% of women diagnosed with endometrial cancer do not present with PMB. Given the cross-sectional nature of most studies included in this meta-analysis, additional studies linking clinical records with cancer registry data may be warranted to validate our findings. With respect to the analysis of the risk of endometrial cancer in women with PMB, most studies were cross-sectional, and few included prospective follow-up; thus, we were unable to evaluate long-term risk of endometrial cancer in these studies. Finally, our results suggested a lower prevalence of endometrial cancer in retrospective and prospective cohort studies compared with cross-sectional studies. Cross-sectional studies may have been more likely to include women with recurrent bleeding; however, few studies distinguished between incident vs recurrent PMB.

The widespread practice of referring all women with PMB for TVUS and/or endometrial biopsy carries a considerable burden and cost. Given the rise in endometrial cancer incidence and mortality, our findings raise the important question of how to best manage PMB to optimize the benefit of early detection approaches while avoiding unnecessary harms. Interest has increased in the use of biomarkers, such as DNA methylation, to improve early detection of endometrial cancer. 31 , 32 , 170 , 171 To obtain reliable estimates of the clinical performance of molecular assays, diagnostic tests, and management algorithms, we must know the prior risk of endometrial cancer in the population. 29 , 172

Our study represents an important and timely evaluation of the risk of endometrial cancer in women with PMB and can serve as a reliable reference for the prevalence of PMB in women with endometrial cancer and the risk of endometrial cancer in women with PMB, 2 requisite prior probabilities for prediction of endometrial cancer risk and secondary and tertiary prevention. As new markers are discovered or new clinical management strategies are evaluated, our results can aid in the assessment of their potential clinical value and will help to inform clinical and epidemiologic risk prediction models to support clinical decision making.

Accepted for Publication: May 3, 2018.

Corresponding Author: Megan A. Clarke, PhD, MHS, Division of Cancer Epidemiology and Genetics, National Cancer Institute, 9609 Medical Center Dr, Room 6E552, Rockville, MD 20850 ( [email protected] ).

Published Online: August 6, 2018. doi:10.1001/jamainternmed.2018.2820

Author Contributions: Dr Clarke had full access to the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Concept and design: Long, Bakkum-Gamez, Wentzensen.

Acquisition, analysis, or interpretation of data: All authors.

Drafting of the manuscript: Clarke, Bakkum-Gamez, Wentzensen.

Critical revision of the manuscript for important intellectual content: Long, Del Mar Morillo, Arbyn, Bakkum-Gamez, Wentzensen.

Statistical analysis: Clarke, Wentzensen.

Administrative, technical, or material support: Wentzensen.

Supervision: Bakkum-Gamez, Wentzensen.

Conflict of Interest Disclosures: None reported.

Funding/Support: This study was supported by grant 603019 via the COHEAHR Network, 7th Framework Programme of DG Research and Innovation, European Commission (Dr Arbyn).

Role of the Funder/Sponsor: The funding source had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

Additional Contributions: Barbara Brandys, BASc, Office of Research Services, National Institutes of Health Library, assisted with the literature search. She was not compensated for this work.

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A serum lipidomics study for the identification of specific biomarkers for endometrial polyps to distinguish them from endometrial cancer or hyperplasia

Affiliations.

• 1 School of Chinese Materia Medica, Tianjin University of Traditional Chinese Medicine, Tianjin, China.
• 2 Department of Gynaecology and Obstetrics, People's Hospital of Guangrao County, Dongying, Shandong, China.
• 3 Department of Kidney Disease and Blood Purification, The Second Hospital of Tianjin Medical University, Tianjin, China.
• 4 Department of Oncology, Tianjin Institute of Urology, The Second Hospital of Tianjin Medical University, Tianjin, China.
• 5 Hysteroscopic Center, FuXing Hospital, Capital Medical University, Beijing, China.
• PMID: 35076938
• DOI: 10.1002/ijc.33943

Endometrial diseases, including endometrial polyps (EP), endometrial cancer (EC) and endometrial hyperplasia (EH), are common gynecological diseases that affect women of childbearing and perimenopausal age. Clinically, biopsy or imaging methods are usually used to screen and diagnose these diseases; however, due to the invasiveness and heterogeneity of these tests, a noninvasive, convenient, objective and accurate biomarker is needed for the differential diagnosis of EP, EC or EH. In the present study, serum samples from 326 patients with endometrial diseases and 225 healthy volunteers were analyzed using nontargeted lipidomics. A combination of multivariate and univariate analyses was used to identify and qualify six, eight and seven potential biomarkers in the sera from patients with EP, EC and EH, respectively. Using a logistic regression algorithm and receiver operating characteristic (ROC) curve analysis, a biomarker panel including four specific EP biomarkers, 6-keto-PGF1α, PA(37:4), LysoPC(20:1) and PS(36:0), showed good classification and diagnostic ability in distinguishing EP from EC or EH. The biomarker panel for distinguishing EP from EC yielded an area under the curve (AUC) of 0.915, sensitivity of 100% and specificity of 72.41%, while that for distinguishing EP from EH yielded an AUC of 1.000, sensitivity of 100% and specificity of 100%. The two diagnostic models also showed good diagnostic abilities in the validation set. Therefore, this biomarker panel can be used as a rapid diagnostic method to assist in imaging examinations and provide a reference for clinicians in the identification and diagnosis of endometrial diseases.

Keywords: diagnostic biomarkers; endometrial cancer; endometrial diseases; lipidomics; serum metabolites.

© 2022 UICC.

Publication types

• Research Support, Non-U.S. Gov't
• Biomarkers, Tumor
• Endometrial Hyperplasia* / diagnosis
• Endometrial Hyperplasia* / pathology
• Endometrial Neoplasms* / diagnosis
• Endometrial Neoplasms* / pathology
• Hyperplasia
• Uterine Diseases*

RSC Medicinal Chemistry

Small molecule targeted therapies for endometrial cancer: progress, challenges, and opportunities.

* Corresponding authors

a Yixing People's Hospital, Yixing, Jiangsu, China

b School of Life Sciences and Health Engineering, Jiangnan University, Wuxi, China E-mail: [email protected]

c Xishan People's Hospital of Wuxi City, Wuxi, Jiangsu, China E-mail: [email protected]

d Department of Pharmaceutical and Chemical Industries, Higher Institute of Applied Science and Technology, Damascus, Syria

Endometrial cancer (EC) is a common malignancy among women worldwide, and its recurrence makes it a common cause of cancer-related death. Surgery and external radiation, chemotherapy, or a combination of strategies are the cornerstone of therapy for EC patients. However, adjuvant treatment strategies face certain drawbacks, such as resistance to chemotherapeutic drugs; therefore, it is imperative to explore innovative therapeutic strategies to improve the prognosis of EC. With the development of pathology and pathophysiology, several biological targets associated with EC have been identified, including PI3K/Akt/mTOR, PARP, GSK-3β, STAT-3, and VEGF. In this review, we summarize the progress of small molecule targeted therapies in terms of both basic research and clinical trials and provide cases of small molecules combined with fluorescence properties in the clinical applications of integrated diagnosis and treatment. We hope that this review will facilitate the further understanding of the regulatory mechanism governing the dysregulation of oncogenic signaling in EC and provide insights into the possible future directions of targeted therapeutic regimens for EC treatment by developing new agents with fluorescence properties for the clinical applications of integrated diagnosis and treatment.

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Dissertations / Theses on the topic 'Endometrial cancer'

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Wang, Yiying, Yue Wang, Jie Li, Janiel Cragun, Kenneth Hatch, Setsuko Chambers, and Wenxin Zheng. "Lynch syndrome related endometrial cancer: clinical significance beyond the endometrium." BioMed Central, 2013. http://hdl.handle.net/10150/610184.

Cheng, Timothy. "Genetic susceptibility to endometrial cancer." Thesis, University of Oxford, 2015. http://ora.ox.ac.uk/objects/uuid:3a559ae0-156f-48a2-a64e-b03a13c562df.

Kho, Pik Fang. "Genetic epidemiology of endometrial cancer." Thesis, Queensland University of Technology, 2021. https://eprints.qut.edu.au/211383/1/Pik%20Fang_Kho_Thesis.pdf.

Chen, Maxine M. "Genetics and Genomics of Endometrial Cancer." Thesis, Harvard University, 2016. http://nrs.harvard.edu/urn-3:HUL.InstRepos:27201719.

Falck, Eva. "Genomic Alterations in Experimental Endometrial Adenocarcinoma." Licentiate thesis, Högskolan i Skövde, Institutionen för vård och natur, 2012. http://urn.kb.se/resolve?urn=urn:nbn:se:his:diva-7419.

魏燕萍 and Yin-ping Ngai. "p21-activated kinases in endometrial carcinoma." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2008. http://hub.hku.hk/bib/B40738528.

Wedrén, Sara. "Genetic susceptibility to breast and endometrial cancer /." Stockholm, 2004. http://diss.kib.ki.se/2004/91-7140-053-2/.

鄧國全 and Kwok-tsuen Dang. "Methylation status of endometrial cancer related genes." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2002. http://hub.hku.hk/bib/B31970497.

Nickkho-Amiry, Mahshid. "Peroxisome proliferator-activated receptors in endometrial cancer." Thesis, University of Manchester, 2011. https://www.research.manchester.ac.uk/portal/en/theses/peroxisome-proliferatoractivated-receptors-in-endometrial-cancer(2388ac43-ecd4-402f-a9c7-853be4902ec8).html.

Dang, Kwok-tsuen. "Methylation status of endometrial cancer related genes." Hong Kong : University of Hong Kong, 2002. http://sunzi.lib.hku.hk/hkuto/record.jsp?B25549583.

Dowdy, Janet A. "Effects of acetaminophen on estrogen-responsive alkaline phosphatase in Ishikawa endometrial cancer cells." Morgantown, W. Va. : [West Virginia University Libraries], 2000. http://etd.wvu.edu/templates/showETD.cfm?recnum=1565.

陳君怡 and Kwan-yi Queeny Chan. "Molecular studies on endometrial and ovarian carcinogenesis." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2007. http://hub.hku.hk/bib/B39634474.

Tonon, Ângela Favorito Santarém [UNESP]. "Claudina-3 e Claudina- 4, potenciais marcadores de agressividade no carcinoma endometrial Tipo I." Universidade Estadual Paulista (UNESP), 2013. http://hdl.handle.net/11449/108608.

Einarsdóttir, Kristjana. "Genetic determinants of postmenopausal breast and endometrial cancer /." Stockholm : Karolinska institutet, 2007. http://diss.kib.ki.se/2007/978-91-7357-037-4/.

Holland, C. M. "Genomic and post-genomic studies in endometrial cancer." Thesis, University of Cambridge, 2004. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.604158.

Naftalin, J. G. "Ultrasound studies of the endometrial-myometrial junction for the diagnosis of adenomyosis and endometrial cancer." Thesis, University College London (University of London), 2014. http://discovery.ucl.ac.uk/1432603/.

Koutoukidis, D. "Diet, nutrition and physical activity in endometrial cancer survivors." Thesis, University College London (University of London), 2017. http://discovery.ucl.ac.uk/1539075/.

Chedumbarum, Pillay O. D. "The association between polycystic ovary syndrome and endometrial cancer." Thesis, University College London (University of London), 2010. http://discovery.ucl.ac.uk/19981/.

Kalogera, Eleftheria. "Quinacrine in endometrial cancer| Repurposing an old antimalarial drug." Thesis, College of Medicine - Mayo Clinic, 2016. http://pqdtopen.proquest.com/#viewpdf?dispub=10111530.

Background and Rationale: Although the majority of patients with endometrial cancer (EC) are diagnosed early when disease is confined in the uterus and prognosis is excellent, there is a subset of patients with dismal prognosis. Carboplatin and paclitaxel is the standard chemotherapeutic regimen for EC. Given that response to chemotherapy impacts disease prognosis, especially in advanced, recurrent and metastatic disease, novel chemotherapeutic agents with improved safety profile are necessary to improve response rates and outcomes in these patients. Quinacrine (QC) is an inexpensive antimalarial drug with a predictable safety profile which recently surfaced as a promising anticancer agent thought to be associated with decreased risk of developing chemo-resistance through targeting multiple pathways simultaneously.

Objective: To generate preclinical data on the effect of QC in inhibiting tumorigenesis in EC both in vitro and in vivo as well as explore its role as an adjunct to standard chemotherapy in vivo in an EC mouse xenograft model.

Methods: Five different EC cell lines (Ishikawa, Hec-1B, KLE, ARK-2, and SPEC-2) representing different histologies, grades of EC, sensitivity to cisplatin and p53 status were used for the in vitro studies. MTT and colony formation assays were used to examine QC’s ability to inhibit cell viability in vitro. Drug combination studies were performed and the Chou-Talalay methodology was employed in order to examine synergism between QC and cisplatin, carboplatin or paclitaxel. A cisplatin-resistant EC subcutaneous mouse xenograft model was used in order to explore QC’s anticancer activity in vivo and assess its role as maintenance therapy.

Results: QC exhibited strong synergism in vitro when combined with cisplatin, carboplatin or paclitaxel with the highest level of the synergism being observed in the most chemo-resistant EC cell line. Neither QC monotherapy nor standard chemotherapy significantly delayed tumor growth in the mouse xenografts. Co-administration of QC with standard chemotherapy significantly augmented the antiproliferative ability of these chemotherapeutic agents as evidenced by the significant decrease in tumor burden. Combination treatment was associated with a 14-week prolongation of median survival compared to standard chemotherapy alone. Maintenance therapy with QC following standard chemotherapy was proven superior to standard chemotherapy as it resulted in long-term stabilization of disease evidenced by lack of significant tumor progression and further prolongation of overall survival. QC treatment alone, in combination with standard chemotherapy or as maintenance therapy was well-tolerated and was not associated with weight loss compared to control mice. A yellow skin discoloration was noted during active treatment with QC which was entirely reversible within a few days upon discontinuation of treatment.

Conclusions: QC exhibited significant antitumor activity against EC cell lines in vitro and was successful as maintenance therapy in chemo-resistant EC mouse xenografts. This preclinical data suggest that QC may be an important adjunct to standard platinum-based chemotherapeutic regimens for patients with recurrent EC.

Crosland, Rachel. "Studies of the PTEN tumour suppressor in endometrial cancer." Thesis, Sheffield Hallam University, 2004. http://shura.shu.ac.uk/19515/.

Ziou, Arisa. "Gene expression of MYPT1 and ROCK1 in endometrial cancer." Thesis, Högskolan i Skövde, Institutionen för hälsovetenskaper, 2015. http://urn.kb.se/resolve?urn=urn:nbn:se:his:diva-19249.

Haughian, James M. "Defining protein kinase C function in endometrial cancer cells /." Connect to full text via ProQuest. Limited to UCD Anschutz Medical Campus, 2008. http://proquest.umi.com/pqdweb?did=1545964851&sid=2&Fmt=6&clientId=18952&RQT=309&VName=PQD.

Hill, Deirdre A. "Hormone use patterns, intrauterine device use, and endometrial cancer /." Thesis, Connect to this title online; UW restricted, 1997. http://hdl.handle.net/1773/10899.

Kamal, A. M. "Endometrial cancer : involvement of androgens and metastasis inducing proteins." Thesis, University of Liverpool, 2016. http://livrepository.liverpool.ac.uk/3004396/.

Sivalingam, Vanitha. "The role of metformin in obesity-driven endometrial cancer." Thesis, University of Manchester, 2016. https://www.research.manchester.ac.uk/portal/en/theses/the-role-of-metformin-in-obesitydriven-endometrial-cancer(5a4418b9-5dab-4e6a-be05-9180996073c1).html.

Juraskova, Ilona. "Psycho-sexual adjustment following treatment for early stage cervical and endometrial cancer." Phd thesis, School of Psychology, 2003. http://hdl.handle.net/2123/3928.

Wang, Yue, and 王悦. "Molecular analysis of mitochondrial DNA alterations in endometrial carcinomas." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2005. http://hub.hku.hk/bib/B32059127.

Davis, Warren. "Bioactivation of tamoxifen : its metabolites and metabolites to genotoxic species." Thesis, University of London, 1999. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.314343.

Jurcevic, Sanja. "MicroRNA expression profiling in endometrial adenocarcinoma." Doctoral thesis, Örebro universitet, Institutionen för hälsovetenskap och medicin, 2015. http://urn.kb.se/resolve?urn=urn:nbn:se:oru:diva-41640.

Fearon, Abbie Elizabeth. "Dissection of drug resistance mechanisms in FGFR2 mutant endometrial cancer." Thesis, Queen Mary, University of London, 2015. http://qmro.qmul.ac.uk/xmlui/handle/123456789/9027.

Sahbai, Samine [Verfasser]. "Scintigraphic detection of sentinel nodes in endometrial cancer / Samine Sahbai." Tübingen : Universitätsbibliothek Tübingen, 2019. http://d-nb.info/1227963939/34.

Denu, Stefanie. "Impact of Acceptance and Body Compassion in Endometrial Cancer Patients." Xavier University / OhioLINK, 2018. http://rave.ohiolink.edu/etdc/view?acc_num=xavier1531398277520261.

Hovey, Adriann Marie. "Characterization of miR-888 expression and regulation in endometrial cancer." Diss., University of Iowa, 2014. https://ir.uiowa.edu/etd/4649.

Geng, Xinyan. "Investigations into how best to target FGFR2 mutant endometrial cancer." Thesis, Queensland University of Technology, 2017. https://eprints.qut.edu.au/123437/1/Xinyan%20Geng%20Thesis.pdf.

Wallace, Alison E. "F-prostanoid receptor regulation of inflammation in endometrial adenocarcinoma." Thesis, University of Edinburgh, 2010. http://hdl.handle.net/1842/4447.

Devis, Jauregui Laura. "The role of activated leukocyte cell adhesion molecule (ALCAM) in endometrial cancer progression and dissemination." Doctoral thesis, Universitat Autònoma de Barcelona, 2017. http://hdl.handle.net/10803/403809.

Doherty, Jennifer Anne. "Genetic influences on estrogen biosynthesis, catabolism, and response in relation to the incidence of endometrial cancer /." Thesis, Connect to this title online; UW restricted, 2002. http://hdl.handle.net/1773/10869.

Chan, Kwan-yi Queeny, and 陳君怡. "Molecular study of pi-class glutathione-S-transferase in endometrial carcinoma." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2003. http://hub.hku.hk/bib/B29157717.

Campoy, Moncayo Irene. "Exosomes in uterine aspirates: characterization and identification of diagnostic and prognostic biomarkers in endometrial cancer." Doctoral thesis, Universitat Autònoma de Barcelona, 2017. http://hdl.handle.net/10803/458138.

Eskiocak, Ugur. "Investigation Of Telomerase Activity In Diagnosis Of Endometrial And Cervical Cancer." Master's thesis, METU, 2007. http://etd.lib.metu.edu.tr/upload/12608507/index.pdf.

Hughes, Cathy. "Women's experience of laparoscopic surgery in endometrial cancer : a phenomenological study." Thesis, University of Surrey, 2009. http://epubs.surrey.ac.uk/843057/.

Voigt, Lynda F. "Exogenous hormone use and other risk factors associated with endometrial cancer /." Thesis, Connect to this title online; UW restricted, 1990. http://hdl.handle.net/1773/10888.

Kularatne, B. Y. "The identification of novel biomarkers to guide treatment in endometrial cancer." Thesis, University College London (University of London), 2017. http://discovery.ucl.ac.uk/1558772/.

Chadwick, Robert B. "Characterization and analysis of genes involved in colorectal and endometrial cancer /." The Ohio State University, 2000. http://rave.ohiolink.edu/etdc/view?acc_num=osu1488199501402734.

Kang, Hyun Sook. "GPR54 is a target for suppression of metastasis in endometrial cancer." Kyoto University, 2011. http://hdl.handle.net/2433/142549.

Tse, Ka-yu, and 謝嘉瑜. "Identification of novel methylated genes in patients with endometrial cancers." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2007. http://hub.hku.hk/bib/B45011473.

Martínez, García Elena. "Protein signatures in uterine aspirates to improve diagnosis of endometrial cancer "The CEMARK project"." Doctoral thesis, Universitat Autònoma de Barcelona, 2017. http://hdl.handle.net/10803/458514.

Liao, Xiaoyun, and 廖晓耘. "Hedgehog signaling pathway and epigenetic studies in ovarian carcinomas and endometrial carcinomas." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2008. http://hub.hku.hk/bib/B41290367.

Hernández, Adrian V., Vinay Pasupuleti, Zapata Vicente A. Benites, Priyaleela Thota, Abhishek Deshpande, and Lopez Faustino R. Perez. "Insulin resistance and endometrial cancer risk: A systematic review and meta-analysis." Elsevier B.V, 2015. http://hdl.handle.net/10757/582697.

Hernandez, Adrian V., Vinay Pasupuleti, Vicente A. Benítes-Zapata, Priyaleela Thota, Abhishek Deshpande, and Lopez Faustino R. Perez. "Insulin resistance and endometrial cancer risk: A systematic review and meta-analysis." Elsevier B.V, 2015. http://hdl.handle.net/10757/621216.

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Theses & Dissertations: Cancer Research

Theses/dissertations from 2024 2024.

Novel Spirocyclic Dimer (SpiD3) Displays Potent Preclinical Effects in Hematological Malignancies , Alexandria Eiken

Therapeutic Effects of BET Protein Inhibition in B-cell Malignancies and Beyond , Audrey L. Smith

Identifying the Molecular Determinants of Lung Metastatic Adaptation in Prostate Cancer , Grace M. Waldron

Identification of Mitotic Phosphatases and Cyclin K as Novel Molecular Targets in Pancreatic Cancer , Yi Xiao

Theses/Dissertations from 2023 2023

Development of Combination Therapy Strategies to Treat Cancer Using Dihydroorotate Dehydrogenase Inhibitors , Nicholas Mullen

Overcoming Resistance Mechanisms to CDK4/6 Inhibitor Treatment Using CDK6-Selective PROTAC , Sarah Truong

Theses/Dissertations from 2022 2022

Omics Analysis in Cancer and Development , Emalie J. Clement

Investigating the Role of Splenic Macrophages in Pancreatic Cancer , Daisy V. Gonzalez

Polymeric Chloroquine in Metastatic Pancreatic Cancer Therapy , Rubayat Islam Khan

Evaluating Targets and Therapeutics for the Treatment of Pancreatic Cancer , Shelby M. Knoche

Characterization of 1,1-Diarylethylene FOXM1 Inhibitors Against High-Grade Serous Ovarian Carcinoma Cells , Cassie Liu

Novel Mechanisms of Protein Kinase C α Regulation and Function , Xinyue Li

SOX2 Dosage Governs Tumor Cell Identity and Proliferation , Ethan P. Metz

Post-Transcriptional Control of the Epithelial-to-Mesenchymal Transition (EMT) in Ras-Driven Colorectal Cancers , Chaitra Rao

Use of Machine Learning Algorithms and Highly Multiplexed Immunohistochemistry to Perform In-Depth Characterization of Primary Pancreatic Tumors and Metastatic Sites , Krysten Vance

Characterization of Metastatic Cutaneous Squamous Cell Carcinoma in the Immunosuppressed Patient , Megan E. Wackel

Visceral adipose tissue remodeling in pancreatic ductal adenocarcinoma cachexia: the role of activin A signaling , Pauline Xu

Phos-Tag-Based Screens Identify Novel Therapeutic Targets in Ovarian Cancer and Pancreatic Cancer , Renya Zeng

Theses/Dissertations from 2021 2021

Functional Characterization of Cancer-Associated DNA Polymerase ε Variants , Stephanie R. Barbari

Pancreatic Cancer: Novel Therapy, Research Tools, and Educational Outreach , Ayrianne J. Crawford

Apixaban to Prevent Thrombosis in Adult Patients Treated With Asparaginase , Krishna Gundabolu

Molecular Investigation into the Biologic and Prognostic Elements of Peripheral T-cell Lymphoma with Regulators of Tumor Microenvironment Signaling Explored in Model Systems , Tyler Herek

Utilizing Proteolysis-Targeting Chimeras to Target the Transcriptional Cyclin-Dependent Kinases 9 and 12 , Hannah King

Insights into Cutaneous Squamous Cell Carcinoma Pathogenesis and Metastasis Using a Bedside-to-Bench Approach , Marissa Lobl

Development of a MUC16-Targeted Near-Infrared Antibody Probe for Fluorescence-Guided Surgery of Pancreatic Cancer , Madeline T. Olson

FGFR4 glycosylation and processing in cholangiocarcinoma promote cancer signaling , Andrew J. Phillips

Theses/Dissertations from 2020 2020

Cooperativity of CCNE1 and FOXM1 in High-Grade Serous Ovarian Cancer , Lucy Elge

Characterizing the critical role of metabolic and redox homeostasis in colorectal cancer , Danielle Frodyma

Genomic and Transcriptomic Alterations in Metabolic Regulators and Implications for Anti-tumoral Immune Response , Ryan J. King

Dimers of Isatin Derived Spirocyclic NF-κB Inhibitor Exhibit Potent Anticancer Activity by Inducing UPR Mediated Apoptosis , Smit Kour

From Development to Therapy: A Panoramic Approach to Further Our Understanding of Cancer , Brittany Poelaert

The Cellular Origin and Molecular Drivers of Claudin-Low Mammary Cancer , Patrick D. Raedler

Mitochondrial Metabolism as a Therapeutic Target for Pancreatic Cancer , Simon Shin

Development of Fluorescent Hyaluronic Acid Nanoparticles for Intraoperative Tumor Detection , Nicholas E. Wojtynek

Theses/Dissertations from 2019 2019

The role of E3 ubiquitin ligase FBXO9 in normal and malignant hematopoiesis , R. Willow Hynes-Smith

BRCA1 & CTDP1 BRCT Domainomics in the DNA Damage Response , Kimiko L. Krieger

Targeted Inhibition of Histone Deacetyltransferases for Pancreatic Cancer Therapy , Richard Laschanzky

Human Leukocyte Antigen (HLA) Class I Molecule Components and Amyloid Precursor-Like Protein 2 (APLP2): Roles in Pancreatic Cancer Cell Migration , Bailee Sliker

Theses/Dissertations from 2018 2018

FOXM1 Expression and Contribution to Genomic Instability and Chemoresistance in High-Grade Serous Ovarian Cancer , Carter J. Barger

Overcoming TCF4-Driven BCR Signaling in Diffuse Large B-Cell Lymphoma , Keenan Hartert

Functional Role of Protein Kinase C Alpha in Endometrial Carcinogenesis , Alice Hsu

Functional Signature Ontology-Based Identification and Validation of Novel Therapeutic Targets and Natural Products for the Treatment of Cancer , Beth Neilsen

Elucidating the Roles of Lunatic Fringe in Pancreatic Ductal Adenocarcinoma , Prathamesh Patil

Theses/Dissertations from 2017 2017

Metabolic Reprogramming of Pancreatic Ductal Adenocarcinoma Cells in Response to Chronic Low pH Stress , Jaime Abrego

Understanding the Relationship between TGF-Beta and IGF-1R Signaling in Colorectal Cancer , Katie L. Bailey

The Role of EHD2 in Triple-Negative Breast Cancer Tumorigenesis and Progression , Timothy A. Bielecki

Perturbing anti-apoptotic proteins to develop novel cancer therapies , Jacob Contreras

Role of Ezrin in Colorectal Cancer Cell Survival Regulation , Premila Leiphrakpam

Evaluation of Aminopyrazole Analogs as Cyclin-Dependent Kinase Inhibitors for Colorectal Cancer Therapy , Caroline Robb

Identifying the Role of Janus Kinase 1 in Mammary Gland Development and Breast Cancer , Barbara Swenson

DNMT3A Haploinsufficiency Provokes Hematologic Malignancy of B-Lymphoid, T-Lymphoid, and Myeloid Lineage in Mice , Garland Michael Upchurch

Theses/Dissertations from 2016 2016

EHD1 As a Positive Regulator of Macrophage Colony-Stimulating Factor-1 Receptor , Luke R. Cypher

Inflammation- and Cancer-Associated Neurolymphatic Remodeling and Cachexia in Pancreatic Ductal Adenocarcinoma , Darci M. Fink

Role of CBL-family Ubiquitin Ligases as Critical Negative Regulators of T Cell Activation and Functions , Benjamin Goetz

Exploration into the Functional Impact of MUC1 on the Formation and Regulation of Transcriptional Complexes Containing AP-1 and p53 , Ryan L. Hanson

DNA Polymerase Zeta-Dependent Mutagenesis: Molecular Specificity, Extent of Error-Prone Synthesis, and the Role of dNTP Pools , Olga V. Kochenova

Defining the Role of Phosphorylation and Dephosphorylation in the Regulation of Gap Junction Proteins , Hanjun Li

Molecular Mechanisms Regulating MYC and PGC1β Expression in Colon Cancer , Jamie L. McCall

Pancreatic Cancer Invasion of the Lymphatic Vasculature and Contributions of the Tumor Microenvironment: Roles for E-selectin and CXCR4 , Maria M. Steele

Altered Levels of SOX2, and Its Associated Protein Musashi2, Disrupt Critical Cell Functions in Cancer and Embryonic Stem Cells , Erin L. Wuebben

Theses/Dissertations from 2015 2015

Characterization and target identification of non-toxic IKKβ inhibitors for anticancer therapy , Elizabeth Blowers

Effectors of Ras and KSR1 dependent colon tumorigenesis , Binita Das

Characterization of cancer-associated DNA polymerase delta variants , Tony M. Mertz

A Role for EHD Family Endocytic Regulators in Endothelial Biology , Alexandra E. J. Moffitt

Biochemical pathways regulating mammary epithelial cell homeostasis and differentiation , Chandrani Mukhopadhyay

EPACs: epigenetic regulators that affect cell survival in cancer. , Catherine Murari

Role of the C-terminus of the Catalytic Subunit of Translesion Synthesis Polymerase ζ (Zeta) in UV-induced Mutagensis , Hollie M. Siebler

LGR5 Activates TGFbeta Signaling and Suppresses Metastasis in Colon Cancer , Xiaolin Zhou

LGR5 Activates TGFβ Signaling and Suppresses Metastasis in Colon Cancer , Xiaolin Zhou

Theses/Dissertations from 2014 2014

Genetic dissection of the role of CBL-family ubiquitin ligases and their associated adapters in epidermal growth factor receptor endocytosis , Gulzar Ahmad

Strategies for the identification of chemical probes to study signaling pathways , Jamie Leigh Arnst

Defining the mechanism of signaling through the C-terminus of MUC1 , Roger B. Brown

Targeting telomerase in human pancreatic cancer cells , Katrina Burchett

The identification of KSR1-like molecules in ras-addicted colorectal cancer cells , Drew Gehring

Mechanisms of regulation of AID APOBEC deaminases activity and protection of the genome from promiscuous deamination , Artem Georgievich Lada

Characterization of the DNA-biding properties of human telomeric proteins , Amanda Lakamp-Hawley

Studies on MUC1, p120-catenin, Kaiso: coordinate role of mucins, cell adhesion molecules and cell cycle players in pancreatic cancer , Xiang Liu

Epac interaction with the TGFbeta PKA pathway to regulate cell survival in colon cancer , Meghan Lynn Mendick

Theses/Dissertations from 2013 2013

Deconvolution of the phosphorylation patterns of replication protein A by the DNA damage response to breaks , Kerry D. Brader

Modeling malignant breast cancer occurrence and survival in black and white women , Michael Gleason

The role of dna methyltransferases in myc-induced lymphomagenesis , Ryan A. Hlady

Design and development of inhibitors of CBL (TKB)-protein interactions , Eric A. Kumar

Pancreatic cancer-associated miRNAs : expression, regulation and function , Ashley M. Mohr

Mechanistic studies of mitochondrial outer membrane permeabilization (MOMP) , Xiaming Pang

Novel roles for JAK2/STAT5 signaling in mammary gland development, cancer, and immune dysregulation , Jeffrey Wayne Schmidt

Optimization of therapeutics against lethal pancreatic cancer , Joshua J. Souchek

Theses/Dissertations from 2012 2012

Immune-based novel diagnostic mechanisms for pancreatic cancer , Michael J. Baine

Sox2 associated proteins are essential for cell fate , Jesse Lee Cox

KSR2 regulates cellular proliferation, transformation, and metabolism , Mario R. Fernandez

Discovery of a novel signaling cross-talk between TPX2 and the aurora kinases during mitosis , Jyoti Iyer

Regulation of metabolism by KSR proteins , Paula Jean Klutho

The role of ERK 1/2 signaling in the dna damage-induced G2 , Ryan Kolb

Regulation of the Bcl-2 family network during apoptosis induced by different stimuli , Hernando Lopez

Studies on the role of cullin3 in mitosis , Saili Moghe

Characteristics of amyloid precursor-like protein 2 (APLP2) in pancreatic cancer and Ewing's sarcoma , Haley Louise Capek Peters

Structural and biophysical analysis of a human inosine triphosphate pyrophosphatase polymorphism , Peter David Simone

Functions and regulation of Ron receptor tyrosine kinase in human pancreatic cancer and its therapeutic applications , Yi Zou

Theses/Dissertations from 2011 2011

Coordinate detection of new targets and small molecules for cancer therapy , Kurt Fisher

The role of c-Myc in pancreatic cancer initiation and progression , Wan-Chi Lin

The role of inosine triphosphate pyrophosphatase (ITPA) in maintanence [sic] of genomic stability in human cells , Miriam-Rose Menezes

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