Identifying High-Risk Women for Endometrial Cancer Prevention Strategies: Proposal of an Endometrial Cancer Risk Prediction Model

Kitson, Sarah; Evans, D. Gareth; Crosbie, Emma J.

doi:10.1158/1940-6207.capr-16-0224

Cited by 72 publications

(92 citation statements)

References 91 publications

(68 reference statements)

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“…The risk models further included variables related to the reproductive history of women, hormone use, and smoking. All these predictors are known for the relation with developing endometrial cancer (Smith et al, 2003;Beral et al, 2005;Lesko et al, 1985;Hinkula et al, 2002;Kitson et al, 2017). The relation between age and the development of several types of cancer has been most extensively described (DePinho, 2000;Balducci and Ershler, 2005;Anisimov, 2003).…”

Section: Discussionmentioning

confidence: 99%

Prediction models for endometrial cancer for the general population or symptomatic women: A systematic review

Alblas

Velt

Pashayan

et al. 2018

Critical Reviews in Oncology/Hematology

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Objective: To provide an overview of prediction models for the risk of developing endometrial cancer in women of the general population or for the presence of endometrial cancer in symptomatic women. Methods: We systematically searched the Embase and Pubmed database until September 2017 for relevant publications. We included studies describing the development, the external validation, or the updating of a multivariable model for predicting endometrial cancer in the general population or symptomatic women. Results: Out of 2756 references screened, 14 studies were included. We found two prediction models for developing endometrial cancer in the general population (risk models) and one extension. Eight studies described the development of models for symptomatic women (diagnostic models), one comparison of the performance of two diagnostic models and two external validation. Sample size varied from 60 (10 with cancer) to 201,811 (855 with cancer) women. The age of the women was included as a predictor in almost all models. The risk models included epidemiological variables related to the reproductive history of women, hormone use, BMI, and smoking history. The diagnostic models also included clinical predictors, such as endometrial thickness and recurrent bleeding. The concordance statistic (c), assessing the discriminative ability, varied from 0.68 to 0.77 in the risk models and from 0.73 to 0.957 in the diagnostic models. Methodological information was often limited, especially on the handling of missing data, and the selection of predictors. One risk model and four diagnostic models were externally validated. Conclusions: Only a few models have been developed to predict endometrial cancer in asymptomatic or symptomatic women. The usefulness of most models is unclear considering methodological shortcomings and lack of external validation. Future research should focus on external validation and extension with new predictors or biomarkers, such as genetic and epigenetic markers.

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Section: Discussionmentioning

confidence: 99%

Prediction models for endometrial cancer for the general population or symptomatic women: A systematic review

Alblas

Velt

Pashayan

et al. 2018

Critical Reviews in Oncology/Hematology

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“…Well‐designed primary endometrial cancer prevention trials are needed to provide robust evidence for risk‐reducing interventions, but these will be very expensive and time consuming. Risk prediction models that refine the population most likely to benefit from targeted prevention strategies are needed to ensure trials are adequately powered and have sufficient follow up to generate clear answers …”

Section: Preventing Obesity‐driven Endometrial Cancermentioning

confidence: 99%

“…Risk prediction models that refine the population most likely to benefit from targeted prevention strategies are needed to ensure trials are adequately powered and have sufficient follow up to generate clear answers. 26…”

Section: Preventing Obesity-driven Endometrial Cancermentioning

confidence: 99%

Endometrial cancer and obesity

Kitson

Crosbie

2019

The Obstetric & Gynaecologis

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Key content Of the 20 most common tumour types, endometrial cancer has the strongest association with obesity. Endometrial cancer should be considered in young, obese women with irregular or heavy menstrual bleeding. To reduce the risk of postoperative complications, surgery for endometrial cancer should be performed using minimal access techniques whenever possible. For women who are unfit for, or who decline, surgery, alternative treatments include progestins or radiotherapy, but these have lower efficacy and are associated with a higher risk of disease relapse. Obesity is associated with reduced overall survival following endometrial cancer because of increased cardiovascular mortality; it may also affect disease‐specific survival. Learning objectives To further understanding of the mechanisms through which obesity drives endometrial carcinogenesis. To improve understanding of the potential difficulties associated with the management of endometrial cancer in obese women. To increase knowledge of alternative treatment options for women who are unfit for, or who decline, standard endometrial cancer management. Ethical issues The number of young, premenopausal women with endometrial cancer is increasing – how should these women be managed? Should super‐obese women with endometrial cancer only be treated in cancer centres? After treating a woman's endometrial cancer, how should she be counselled her about her weight and cardiovascular disease risk?

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“…Already the fourth most common cancer in women, the incidence of endometrial cancer is rising globally as a consequence of the escalating rates of obesity, to which up to 41% of endometrial cancers can be directly attributed (1)(2)(3). Whilst the majority of women present early with postmenopausal bleeding and disease confined to the uterus, there is a marked discrepancy in fiveyear survival between those with stage I disease (95%) and those with stage IV disease (14%) (4).The presence of obesity may also further adversely impact upon prognosis (5).…”

Section: Introductionmentioning

confidence: 99%

Targeting endometrial cancer stem cell activity with metformin is inhibited by patient-derived adipocyte-secreted factors

Kitson

Rosser

Fischer

et al. 2019

Preprint

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PurposeAdvanced endometrial cancer continues to have a poor prognosis due to limited treatment options, which may be further adversely impacted by obesity. Endometrial cancer stem cells have been reported to drive metastasis, chemotherapy resistance and disease relapse, but have yet to be fully characterised and no specific targeted therapies have been identified. Here, we describe the phenotype and genotype of aldehyde dehydrogenase high (ALDH high ) and CD133 +ve endometrial cancer stem cells and how adipocyte secreted mediators block the inhibitory effect of metformin on endometrial cancer stem cell activity. Experimental designIshikawa and Hec-1a cell lines were used to characterise ALDH high and CD133 +ve endometrial cancer cells using flow cytometry, functional sphere assays and quantitative-Polymerase Chain Reaction. The comparative effect of metformin on endometrial cancer stem cell activity and bulk tumour cell proliferation was determined using an Aldefluor and cytotoxicity assay. The impact of adipocyte secreted mediators on metformin response was established using patient-derived conditioned media. ResultsALDH high cells demonstrated greater endometrial cancer stem cell activity than CD133 +ve cells and had increased expression of stem cell and epithelial-mesenchymal transition genes. Treatment with 0.5-1mM metformin reduced the proportion and activity of both endometrial cancer stem cell populations (p≤0.05), without affecting cell viability. This effect was, however, inhibited by exposure to patient-derived adipocyte conditioned media. ConclusionsThese results indicate a selective and specific effect of metformin on endometrial cancer stem cell activity, which is blocked by adipocyte secreted mediators. Future studies of metformin as an adjuvant therapy in endometrial cancer should be adequately powered to investigate the influence of body mass on treatment response.

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Identifying High-Risk Women for Endometrial Cancer Prevention Strategies: Proposal of an Endometrial Cancer Risk Prediction Model

Cited by 72 publications

References 91 publications

Prediction models for endometrial cancer for the general population or symptomatic women: A systematic review

Prediction models for endometrial cancer for the general population or symptomatic women: A systematic review

Endometrial cancer and obesity

Targeting endometrial cancer stem cell activity with metformin is inhibited by patient-derived adipocyte-secreted factors

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