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12 pages, 1026 KiB

Open AccessArticle

Thrombocytosis as a Biomarker in Type II, Non-Endometrioid Endometrial Cancer

by Parker Bussies, Ayi Eta, Andre Pinto, Sophia George and Matthew Schlumbrecht

Cancers 2020, 12(9), 2379; https://doi.org/10.3390/cancers12092379 - 22 Aug 2020

Cited by 3 | Viewed by 2094

Abstract

Thrombocytosis (platelets ≥ 400K) is a common hematologic finding in gynecologic malignancies and associated with worse outcomes. Limited data exist on the prognostic capability of thrombocytosis in women with high-grade endometrial cancer (EC). Our objective was to describe the associations between elevated platelets [...] Read more.

Thrombocytosis (platelets ≥ 400K) is a common hematologic finding in gynecologic malignancies and associated with worse outcomes. Limited data exist on the prognostic capability of thrombocytosis in women with high-grade endometrial cancer (EC). Our objective was to describe the associations between elevated platelets at diagnosis, clinicopathologic features, and survival outcomes among women with high-grade, non-endometrioid EC. A review of the institutional cancer registry was performed to identify these women treated between 2005 and 2017. Sociodemographic, clinical, and outcomes data were collected. Analyses were performed using chi-square tests, Cox proportional hazards models, and the Kaplan–Meier method. A total of 271 women were included in the analysis. A total of 19.3% of women had thrombocytosis at diagnosis. Thrombocytosis was associated with reduced median overall survival (OS) compared with those not displaying thrombocytosis (29.4 months vs. 60 months, p < 0.01). This finding was most pronounced in uterine serous carcinoma (16.4 months with thrombocytosis vs. 34.4 months without, p < 0.01). While non-White women had shorter median OS for the whole cohort in the setting of thrombocytosis (29.4 months vs. 39.6 months, p < 0.01), among those with uterine serous carcinoma (USC), this finding was reversed, with decreased median OS in White women (22.1 vs. 16.4 months, p = 0.01). Thrombocytosis is concluded to have negative associations with OS and patient race. Full article

(This article belongs to the Special Issue Risk Factors for Endometrial Cancer)

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Review

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41 pages, 3470 KiB

Open AccessReview

A Narrative Review of the Role of Diet and Lifestyle Factors in the Development and Prevention of Endometrial Cancer

by Hajar Ku Yasin, Anthony H. Taylor and Thangesweran Ayakannu

Cancers 2021, 13(9), 2149; https://doi.org/10.3390/cancers13092149 - 29 Apr 2021

Cited by 26 | Viewed by 6046

Abstract

Endometrial cancer is the most common cancer affecting the reproductive organs of women living in higher-income countries. Apart from hormonal influences and genetic predisposition, obesity and metabolic syndrome are increasingly recognised as major factors in endometrial cancer risk, due to changes in lifestyle [...] Read more.

Endometrial cancer is the most common cancer affecting the reproductive organs of women living in higher-income countries. Apart from hormonal influences and genetic predisposition, obesity and metabolic syndrome are increasingly recognised as major factors in endometrial cancer risk, due to changes in lifestyle and diet, whereby high glycaemic index and lipid deposition are prevalent. This is especially true in countries where micronutrients, such as vitamins and minerals are exchanged for high calorific diets and a sedentary lifestyle. In this review, we will survey the currently known lifestyle factors, dietary requirements and hormonal changes that increase an individual’s risk for endometrial cancer and discuss their relevance for clinical management. We also examine the evidence that everyday factors and clinical interventions have on reducing that risk, such that informed healthy choices can be made. In this narrative review, we thus summarise the dietary and lifestyle factors that promote and prevent the incidence of endometrial cancer. Full article

(This article belongs to the Special Issue Risk Factors for Endometrial Cancer)

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11 pages, 223 KiB

Open AccessReview

Tamoxifen and Endometrial Cancer: A Janus-Headed Drug

by Günter Emons, Alexander Mustea and Clemens Tempfer

Cancers 2020, 12(9), 2535; https://doi.org/10.3390/cancers12092535 - 07 Sep 2020

Cited by 39 | Viewed by 8623

Abstract

Tamoxifen is a selective estrogen receptor modulator used for the treatment and prevention of estrogen receptor (ER)—positive breast cancer. However, tamoxifen increases the risk of endometrial cancer (EC) by about 2–7 fold, and more aggressive types of EC with poor prognoses are observed [...] Read more.

Tamoxifen is a selective estrogen receptor modulator used for the treatment and prevention of estrogen receptor (ER)—positive breast cancer. However, tamoxifen increases the risk of endometrial cancer (EC) by about 2–7 fold, and more aggressive types of EC with poor prognoses are observed in tamoxifen users. On the other hand, tamoxifen is an efficacious treatment for advanced or recurrent EC with low toxicity. The differential agonistic or antagonistic effects of tamoxifen on ERα are explained by the tissue-specific expression profiles of co-activators and co-repressors of the receptor. The estrogen-agonistic effect of tamoxifen in endometrial cancers can also be explained by the expression of G-protein coupled estrogen receptor 1 (GPER-1), a membrane-bound estrogen receptor for which tamoxifen and other “antiestrogens” are pure agonists. Full article

(This article belongs to the Special Issue Risk Factors for Endometrial Cancer)

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23 pages, 1093 KiB

Open AccessReview

Genetic Susceptibility to Endometrial Cancer: Risk Factors and Clinical Management

by Thilo Dörk, Peter Hillemanns, Clemens Tempfer, Julius Breu and Markus C. Fleisch

Cancers 2020, 12(9), 2407; https://doi.org/10.3390/cancers12092407 - 25 Aug 2020

Cited by 31 | Viewed by 5604

Abstract

Endometrial cancer (EC) is the most common cancer affecting the female reproductive organs in higher-income states. Apart from reproductive factors and excess weight, genetic predisposition is increasingly recognized as a major factor in endometrial cancer risk. Endometrial cancer is genetically heterogeneous: while a [...] Read more.

Endometrial cancer (EC) is the most common cancer affecting the female reproductive organs in higher-income states. Apart from reproductive factors and excess weight, genetic predisposition is increasingly recognized as a major factor in endometrial cancer risk. Endometrial cancer is genetically heterogeneous: while a subgroup of patients belongs to cancer predisposition syndromes (most notably the Lynch Syndrome) with high to intermediate lifetime risks, there are also several common genomic polymorphisms contributing to the spectrum of germline predispositions. Germline variants and somatic events may act in concert to modulate the molecular evolution of the tumor, where mismatch-repair deficiency is common in endometrioid endometrial tumors whereas homologous recombinational repair deficiency has been described for non-endometrioid endometrial tumors. In this review, we will survey the currently known genomic predispositions for endometrial cancer and discuss their relevance for clinical management in terms of counseling, screening and novel treatments. Full article

(This article belongs to the Special Issue Risk Factors for Endometrial Cancer)

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18 pages, 410 KiB

Open AccessReview

Menopausal Hormone Therapy and Risk of Endometrial Cancer: A Systematic Review

by Clemens B. Tempfer, Ziad Hilal, Peter Kern, Ingolf Juhasz-Boess and Günther A. Rezniczek

Cancers 2020, 12(8), 2195; https://doi.org/10.3390/cancers12082195 - 06 Aug 2020

Cited by 36 | Viewed by 4543

Abstract

Background: Menopausal hormone therapy (MHT) is an appropriate treatment for women with the climacteric syndrome. The estrogen component of MHT effectively alleviates climacteric symptoms but also stimulates the endometrium and thus may increase the risk of endometrial cancer (EC). Materials and Methods: We [...] Read more.

Background: Menopausal hormone therapy (MHT) is an appropriate treatment for women with the climacteric syndrome. The estrogen component of MHT effectively alleviates climacteric symptoms but also stimulates the endometrium and thus may increase the risk of endometrial cancer (EC). Materials and Methods: We performed a systematic literature search of the databases PubMed and Cochrane Central Register of Controlled Trials to identify controlled and uncontrolled clinical trials reporting on the prevalence and/or incidence of EC among women using MHT. Results: 31 publications reporting on 21,306 women with EC diagnosed during or after MHT were identified. A significantly reduced risk of EC among continuous-combined (cc)MHT users with synthetic progestins (SPs) was demonstrated in 10/19 studies with odds ratios (ORs)/hazard ratios (HRs) between 0.24 and 0.71. Only one study documented an increased risk of EC among long-term users (≥10 years), not confirmed in three other sub-group analyses of women with ≥6, ≥5, and >10 years of ccMHT use. A significantly increased risk of EC among users of sequential-combined (sc)MHT with SPs was demonstrated in 6/12 studies with ORs/HRs between 1.38 and 4.35. Number of days of progestin per month was a significant modulator of EC risk. A decreased risk of EC was seen in obese women. Two studies documented an increased risk of EC among users of cc/scMHT with micronized progesterone. A significantly increased risk of EC among estrogen-only MHT users was demonstrated in 9/12 studies with ORs/HRs between 1.45 and 4.46. The adverse effect of estrogen-only MHT was greatest among obese women. Conclusion: ccMHT with SPs reduces the risk of EC, whereas estrogen-only MHT increases the risk. scMHT with SPs and cc/scMHT with micronized progesterone increase the risk of EC depending on type of progestin, progestin dosage, and duration of MHT use. Full article

(This article belongs to the Special Issue Risk Factors for Endometrial Cancer)

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10 pages, 218 KiB

Open AccessReview

Endocrine Risk Factors of Endometrial Cancer: Polycystic Ovary Syndrome, Oral Contraceptives, Infertility, Tamoxifen

by Atanas Ignatov and Olaf Ortmann

Cancers 2020, 12(7), 1766; https://doi.org/10.3390/cancers12071766 - 02 Jul 2020

Cited by 39 | Viewed by 6082

Abstract

Endometrial cancer is the most common gynecologic cancer and is predominantly endocrine-related. The role of unopposed estrogen in the development of endometrial cancer has been investigated in numerous studies. Different reproductive factors such as younger age at menarche, late age at menopause, infertility, [...] Read more.

Endometrial cancer is the most common gynecologic cancer and is predominantly endocrine-related. The role of unopposed estrogen in the development of endometrial cancer has been investigated in numerous studies. Different reproductive factors such as younger age at menarche, late age at menopause, infertility, nulliparity, age of birth of the first child, and long-term use of unopposed estrogens during hormone replacement therapy have been associated with an increased risk of endometrial cancer. In contrast, there is a growing body of evidence for a protective role of oral contraceptives. Most of the published data on the association between infertility and polycystic ovary syndrome are inconclusive, whereas the effect of tamoxifen on the risk of endometrial cancer has been well established. With this review, we aim to summarize the evidence on the association between infertility, polycystic ovary syndrome, oral contraceptives, and tamoxifen and the development of endometrial cancer. Full article

(This article belongs to the Special Issue Risk Factors for Endometrial Cancer)

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11 pages, 797 KiB

Open AccessCommentary

Obesity Epidemic—The Underestimated Risk of Endometrial Cancer

by Ludwig Kiesel, Christine Eichbaum, Ariane Baumeier and Michael Eichbaum

Cancers 2020, 12(12), 3860; https://doi.org/10.3390/cancers12123860 - 21 Dec 2020

Cited by 10 | Viewed by 2856

Abstract

Endometrial cancer (EC) is the most frequently observed malignant gynecologic disease in developed countries. There is a strong association between the established risk factor obesity and the incidence of EC. Furthermore, the rate of women with a body mass index (BMI) > 30 [...] Read more.

Endometrial cancer (EC) is the most frequently observed malignant gynecologic disease in developed countries. There is a strong association between the established risk factor obesity and the incidence of EC. Furthermore, the rate of women with a body mass index (BMI) > 30 kg/m² is increasing worldwide, correspondingly leading to a higher prevalence of EC. Understanding the adipose tissue as an endocrine organ, elementary pathophysiological pathways of tumorigenesis have been revealed. This includes the fundamental role of hyperglycemia, insulin resistance, and hyperestrogenemia, as well as interactions with a chronic proinflammatory microenvironment. Therapeutic options potentially include metformin or bariatric surgery. Moreover, changes in individual lifestyle such as weight reduction, physical activity, and an awareness of healthy nutrition are effective in preventing the disease. Full article

(This article belongs to the Special Issue Risk Factors for Endometrial Cancer)

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12 pages, 403 KiB

Open AccessPerspective

A Modern Approach to Endometrial Carcinoma: Will Molecular Classification Improve Precision Medicine in the Future?

by Simone Marnitz, Till Walter, Birgid Schömig-Markiefka, Tobias Engler, Stefan Kommoss and Sara Yvonne Brucker

Cancers 2020, 12(9), 2577; https://doi.org/10.3390/cancers12092577 - 10 Sep 2020

Cited by 19 | Viewed by 5171

Abstract

Endometrial cancer has been histologically classified as either an estrogen-dependent cancer with a favorable outcome or an estrogen-independent cancer with a worse prognosis. These parameters, along with the clinical attributions, have been the basis for risk stratification. Recent molecular and histopathological findings have [...] Read more.

Endometrial cancer has been histologically classified as either an estrogen-dependent cancer with a favorable outcome or an estrogen-independent cancer with a worse prognosis. These parameters, along with the clinical attributions, have been the basis for risk stratification. Recent molecular and histopathological findings have suggested a more complex approach to risk stratification. Findings from the Cancer Genome Atlas Research Network established four distinctive genomic groups: ultramutated, hypermutated, copy-number low and copy-number high prognostic subtypes. Subsequently, more molecular and histopathologic classifiers were evaluated for their prognostic and predictive value. The impact of molecular classification is evident and will be recognized by the upcoming WHO classification. Further research is needed to give rise to a new era of molecular-based endometrial carcinoma patient care. Full article

(This article belongs to the Special Issue Risk Factors for Endometrial Cancer)

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