Causal association between aspirin use and risk of endometrioid carcinoma: a Mendelian randomization study.

OBJECTIVE: The aim of the study was to investigate the causal relationship between aspirin use and the risk of endometrial endometrioid cancer (EEC) using two-sample Mendelian randomization (TSMR) and multivariable Mendelian randomization (MVMR) study. MATERIALS AND METHODS: A TSMR analysis was conducted to estimate the potential causal relationship between aspirin use and the risk of EEC using genome-wide data from Genome-wide association study (GWAS). The causal association between aspirin use and EEC was further analyzed by MVMR analysis after adjusting for various factors such as obesity, hypertension, diabetes, and infertility. The single nucleotide polymorphism (SNP) data associated with aspirin use and EEC was obtained from the GWAS catalog database. RESULTS: A total of six SNPs were included as instrumental variables in TSMR, which showed that taking aspirin reduced the risk of EEC [OR = 0.02, 95% CI = 0-0.28, p = 0.005, inverse variance weighted (IVW) method]. Besides, the results of the weighted median (WME) method, weighted mode, and simple mode were consistent with the results shown by the IVW method. After further using the MVMR method, the causal association of aspirin use and prevention of EEC onset remained significant after adjusting for the effects of obesity, hypertension, and diabetes (OR = 0.076, 95% CI = 0.007-0.793, p = 0.031). Sensitivity analyses, including heterogeneity, horizontal multiplicity, and leave-one-out tests, showed the reliability of the instrumental variables, proving that the results were reliable and not significantly biased. CONCLUSIONS: Taking aspirin can reduce the risk of EEC morbidity, and it is expected to be of great significance for the early prevention and treatment of endometrial cancer by exploring the biological mechanism of aspirin on endometrioid cancer at a deeper level.

Latin America and the Caribbean Code Against Cancer 1st Edition: Medical interventions including hormone replacement therapy and cancer screening.

Prostate, breast, colorectal, cervical, and lung cancers are the leading cause of cancer in Latin America and the Caribbean (LAC) accounting for nearly 50% of cancer cases and cancer deaths in the region. Following the IARC Code Against Cancer methodology, a group of Latin American experts evaluated the evidence on several medical interventions to reduce cancer incidence and mortality considering the cancer burden in the region. A recommendation to limit the use of HRT was issued based on the risk associated to develop breast, endometrial, and ovarian cancer and on growing concerns related to the over-the-counter and without prescription sales, which in turn bias estimations on current use in LAC. In alignment with WHO breast and cervical cancer initiatives, biennial screening by clinical breast examination (performed by trained health professionals) from the age of 40 years and biennial screening by mammography from the age of 50 years to 74, as well as cervical screening by HPV testing (either self-sampling or provider-sampling) every 5-10 years for women aged 30-64 years, were recommended. The steadily increasing rates of colorectal cancer in LAC also led to recommend colorectal screening by occult blood testing every two years or by endoscopic examination of the colorectum every 10 years for both men and women aged 50-74 years. After evaluating the evidence, the experts decided not to issue recommendations for prostate and lung cancer screening; while there was insufficient evidence on prostate cancer mortality reduction by prostate-specific antigen (PSA) testing, there was evidence of mortality reduction by low-dose computed tomography (LDCT) targeting high-risk individuals (mainly heavy and/or long-term smokers) but not individuals with average risk to whom recommendations of this Code are directed. Finally, the group of experts adapted the gathered evidence to develop a competency-based online microlearning program for building cancer prevention capacity of primary care health professionals.

Reproductive Events and Risk of Women's Cancers: From Parturition to Prevention.

Reproductive events beginning with pregnancy and ending with remodeling of the breast after cessation of breastfeeding alter breast structure and function and produce dramatic changes in systemic biology. In aggregate, these processes lower overall risk for breast, tubo-ovarian and endometrial cancers, albeit differentially by molecular subtypes of these tumors. Herein, we explore opportunities for research on protective mechanisms operative during this period of the life course, with the goal of encouraging studies to advance cancer prevention. See related article by Getz et al., p. 353.

The Role of Statins in the Prevention of Ovarian and Endometrial Cancers.

Ovarian and endometrial cancers are the most common gynecologic malignancies and emerging evidence suggests that lipid metabolism and subsequent inflammation are important etiologic factors for both tumors. Statins (HMG-CoA reductase inhibitors) are the most widely prescribed lipid-lowering drugs in the United States and are used by 25% of adults aged 40+ years. In addition to their cardio-protective actions, statins have anti-inflammatory effects and have demonstrated antiproliferative and apoptotic properties in cancer cell lines, supporting a potential role in cancer prevention. To appropriately quantify potential public health impact of statin use for cancer prevention, there is a great need to understand the potential risk reduction among individuals at a higher risk of gynecologic cancers, the group that will likely need to be targeted to effectively balance risk/benefit of medications repurposed for cancer prevention. In this commentary, we focus on summarizing emerging evidence suggesting that the anti-inflammatory and lipid-lowering mechanisms of statins may provide important cancer-preventive benefits for gynecologic cancers as well as outline important unanswered questions and future research directions.

Dietary omega-3 fatty acids and endometrial cancer risk in the Epidemiology of Endometrial Cancer Consortium: An individual-participant meta-analysis.

BACKGROUND: Limited data from prospective studies suggest that higher dietary intake of long-chain omega-3 polyunsaturated fatty acids (LCn3PUFA), which hold anti-inflammatory properties, may reduce endometrial cancer risk; particularly among certain subgroups characterized by body mass and tumor pathology. MATERIALS AND METHODS: Data from 12 prospective cohort studies participating in the Epidemiology of Endometrial Cancer Consortium were harmonized as nested case-control studies, including 7268 endometrial cancer cases and 26,133 controls. Habitual diet was assessed by food frequency questionnaire, from which fatty acid intakes were estimated. Two-stage individual-participant data mixed effects meta-analysis estimated adjusted odds ratios (OR) and 95% confidence intervals (CI) through logistic regression for associations between study-specific energy-adjusted quartiles of LCn3PUFA and endometrial cancer risk. RESULTS: Women with the highest versus lowest estimated dietary intakes of docosahexaenoic acid, the most abundant LCn3PUFA in diet, had a 9% increased endometrial cancer risk (Quartile 4 vs. Quartile 1: OR 1.09, 95% CI: 1.01-1.19; P trend = 0.04). Similar elevated risks were observed for the summary measure of total LCn3PUFA (OR 1.07, 95% CI: 0.99-1.16; P trend = 0.06). Stratified by body mass index, higher intakes of LCn3PUFA were associated with 12-19% increased endometrial cancer risk among overweight/obese women and no increased risk among normal-weight women. Higher associations appeared restricted to White women. The results did not differ by cancer grade. CONCLUSION: Higher dietary intakes of LCn3PUFA are unlikely to reduce endometrial cancer incidence; rather, they may be associated with small to moderate increases in risk in some subgroups of women, particularly overweight/obese women.

Germline Mutations Landscape in a Cohort of the State of Minas Gerais, Brazil, in Patients Who Underwent Genetic Counseling for Gynecological and Breast Cancer / Cenário de mutações germinativas em uma coorte do estado de Minas Gerais, Brasil, em pacientes submetidas ao aconselhamento genético para câncer ginecológico e de mama

Abstract Objective The present study evaluated the profile of germline mutations present in patients who underwent genetic counseling for risk assessment for breast cancer (BC), ovarian cancer (OC), and endometrial cancer (EC) with a possible hereditary pattern. Methods Medical records of 382 patients who underwent genetic counseling after signing an informed consent form were analyzed. A total of 55.76% of patients (213/382) were symptomatic (personal history of cancer), and 44.24% (169/382) were asymptomatic (absence of the disease). The variables analyzed were age, sex, place of birth, personal or family history of BC, OC, EC, as well as other types of cancer associated with hereditary syndromes. The Human Genome Variation Society (HGVS) nomenclature guidelines were used to name the variants, and their biological significance was determined by comparing 11 databases. Results We identified 53 distinct mutations: 29 pathogenic variants, 13 variants of undetermined significance (VUS), and 11 benign. The most frequent mutations were BRCA1 c.470_471delCT, BRCA1 c.4675 + 1G > T, and BRCA2 c.2T> G. Furthermore, 21 variants appear to have been described for the first time in Brazil. In addition to BRCA1/2 mutations, variants in other genes related to hereditary syndromes that predispose to gynecological cancers were found. Conclusion This study allowed a deeper understanding of the main mutations identified in families in the state of Minas Gerais and demonstrates the need to assess the family history of non-gynecological cancer for risk assessment of BC, OC, and EC. Moreover, it is an effort that contributes to population studies to evaluate the cancer risk mutation profile in Brazil.

Resumo Objetivo O presente estudo avaliou o perfil de mutações germinativas presentes em pacientes submetidas a aconselhamento genético para avaliação de risco para câncer de mama (CM), câncer de ovário (OC) e câncer de endométrio (CE) com possível padrão hereditário. Métodos Foram analisados os prontuários de 382 pacientes que realizaram aconselhamento genético após consentimento informado. Um total de 55,76% dos pacientes (213/382) eram sintomáticos (história pessoal de câncer), e 44,24% (169/382) eram assintomáticos (ausência da doença). As variáveis analisadas foram idade, sexo, naturalidade, história pessoal ou familiar de CM, OC, CE bem como outros tipos de câncer associados a síndromes hereditárias. As diretrizes de nomenclatura da Human Genome Variation Society (HGVS) foram usadas para nomear as variantes e seu significado biológico foi determinado pela comparação de 11 bancos de dados. Resultados Identificamos 53 mutações distintas: 29 variantes patogênicas, 13 variantes de significado indeterminado e 11 benignas. As mutações mais frequentes foram BRCA1 c.470_471delCT, BRCA1 c.4675 + 1G > T e BRCA2 c.2T > G. Além disso, 21 variantes parecem ter sido descritas pela primeira vez no Brasil. Além das mutações BRCA1/2, foram encontradas variantes em outros genes relacionados a síndromes hereditárias que predispõem a cânceres ginecológicos. Conclusão Este estudo permitiu conhecer melhor as principais mutações identificadas nas famílias do estado de Minas Gerais e demonstra a necessidade de avaliar a história familiar de câncer não ginecológico para avaliação do risco de CM, OC e CE. Além disso, é um esforço que contribui com estudos populacionais para avaliar o perfil de mutações de risco para câncer no Brasil.

Unilateral hydroureteronephrosis after introduction of a levonorgestrel-releasing intrauterine system: a case report and literature review.

Insertion of a LNG-Intra-uterine System (LNG-IUS) has many gynecological indications. The approved indications worldwide are contraception, treatment of abnormal uterine bleeding depending on not organic disease, and endometrial protection in case of an estrogenic therapy. Instead adenomyosis, fibroids, and fertility-sparing management of endometrial hyperplasia or early endometrial cancer in patients with desire of pregnancy are off label indications. Hydroureteronephrosis is an uncommon complication during LNG-IUS insertion. There are few cases described in the literature. The first diagnostic approach for this complication is an abdominal-pelvic ultrasound scan to identify the abnormal position of the device. Diagnostic management includes computed tomography (CT) or magnetic resonance imaging (MRI), which are necessary to confirm hydroureteronephrosis and to assess the exact location of the LNG-IUS in the abdomen. A minimally invasive approach is the standard of care with the removal of the device, while the therapeutic management of the hydroureteronephrosis depends on ureteral and kidney involvement. We report the history of a dislocated LNG-IUS in the left paracervical space with subsequent ipsilateral hydroureteronephrosis. In our case we removed the device through hysteroscopy and later inserted a J-J stent. Follow-up at three months revealed the persistence of left hydroureteronephrosis, so we performed ureter reimplantation. We also performed a review of the literature to analyze common diagnostic and therapeutic pathways for this rare complication.

The influence of dietary vegetables and fruits on endometrial cancer risk: a meta-analysis of observational studies.

Fruits and vegetables store many bioactive compounds and micronutrients, making their consumption ideal for maintaining good health. A previous meta-analysis in 2007 provided evidence that high vegetable and cruciferous vegetable intake might help prevent endometrial cancer (EC) development. The current study purposely explored the favorable effects of vegetables, fruits, and their other specific types using a review of the most recent papers. We conducted a systematic search through August 2021 in the PubMed and EMBASE databases on this topic, through which twenty-seven studies, consisting of 21 case-control and 6 cohort studies, were obtained. The results showed that vegetables (pooled odds ratio [OR], relative risk [RR], hazard ratio [HR] = 0.76, 95% confidence interval [CI] 0.63-0.91), cruciferous vegetables (pooled OR = 0.81, 95% CI 0.70-0.94), dark green and yellow/orange combined vegetables (pooled OR = 0.64, 95% CI 0.42-0.97), and fruits (pooled OR = 0.81, 95% CI 0.70-0.92) were strongly associated with a reduced risk of EC. These results were primarily based on studies of high quality and exhibited either by case-control only or a combination of case-control and cohort studies. Additionally, the results varied by geographic location, such as Western areas, the US, and Italy. This meta-analysis suggested that the consumption of fruits and vegetables has beneficial effects on EC risk and that specific kinds of fruits and vegetables should be recommended differently due to their outstanding bioactive components.

Understanding How Pregnancy Protects Against Ovarian and Endometrial Cancer Development: Fetal Antigens May Be Involved.

It is well known that many factors, including infertility, obesity, type 2 diabetes, and family history of cancer, increase the risk of developing endometrial and ovarian cancer. However, multiparous women are known to have a lower risk of developing either ovarian or endometrial cancer than nonparous women. The lack of ovulation and shifting of sex hormonal balance, with decreased estrogen levels and increased progesterone levels during pregnancy, has traditionally been thought to be the major contributor to this decreased risk. However, in reality, the mechanisms underlying this phenomenon are relatively unknown. Increasing evidence suggests that endocrine factors are unlikely to completely explain the protective effect of pregnancies, and that multiple other nonendocrine mechanisms including fetal antigens and the newly proposed dormant cells hypothesis may also be involved. In this review, we summarize recent evidence and describe the potential underlying mechanisms that may explain how pregnancy protects against the development of ovarian and endometrial cancers in women's later life.

Coffee consumption and risk of endometrial cancer: a pooled analysis of individual participant data in the Epidemiology of Endometrial Cancer Consortium (E2C2).

BACKGROUND: Epidemiologic studies suggest that coffee consumption may be inversely associated with risk of endometrial cancer (EC), the most common gynecological malignancy in developed countries. Furthermore, coffee consumption may lower circulating concentrations of estrogen and insulin, hormones implicated in endometrial carcinogenesis. Antioxidants and other chemopreventive compounds in coffee may have anticarcinogenic effects. Based on available meta-analyses, the World Cancer Research Fund (WCRF) concluded that consumption of coffee probably protects against EC. OBJECTIVES: Our main aim was to examine the association between coffee consumption and EC risk by combining individual-level data in a pooled analysis. We also sought to evaluate potential effect modification by other risk factors for EC. METHODS: We combined individual-level data from 19 epidemiologic studies (6 cohort, 13 case-control) of 12,159 EC cases and 27,479 controls from the Epidemiology of Endometrial Cancer Consortium (E2C2). Logistic regression was used to calculate ORs and their corresponding 95% CIs. All models were adjusted for potential confounders including age, race, BMI, smoking status, diabetes status, study design, and study site. RESULTS: Coffee drinkers had a lower risk of EC than non-coffee drinkers (multiadjusted OR: 0.87; 95% CI: 0.79, 0.95). There was a dose-response relation between higher coffee consumption and lower risk of EC: compared with non-coffee drinkers, the adjusted pooled ORs for those who drank 1, 2-3, and >4 cups/d were 0.90 (95% CI: 0.82, 1.00), 0.86 (95% CI: 0.78, 0.95), and 0.76 (95% CI: 0.66, 0.87), respectively (P-trend < 0.001). The inverse association between coffee consumption and EC risk was stronger in participants with BMI > 25 kg/m2. CONCLUSIONS: The results of the largest analysis to date pooling individual-level data further support the potentially beneficial health effects of coffee consumption in relation to EC, especially among females with higher BMI.

Antioxidative, Anti-Inflammatory, Anti-Obesogenic, and Antidiabetic Properties of Tea Polyphenols-The Positive Impact of Regular Tea Consumption as an Element of Prophylaxis and Pharmacotherapy Support in Endometrial Cancer.

Endometrial cancer (EC) is second only to cervical carcinoma among the most commonly diagnosed malignant tumours of the female reproductive system. The available literature provides evidence for the involvement of 32 genes in the hereditary incidence of EC. The physiological markers of EC and coexisting diet-dependent maladies include antioxidative system disorders but also progressing inflammation; hence, the main forms of prophylaxis and pharmacotherapy ought to include a diet rich in substances aiding the organism's response to this type of disorder, with a particular focus on ones suitable for lifelong consumption. Tea polyphenols satisfy those requirements due to their proven antioxidative, anti-inflammatory, anti-obesogenic, and antidiabetic properties. Practitioners ought to consider promoting tea consumption among individuals genetically predisposed for EC, particularly given its low cost, accessibility, confirmed health benefits, and above all, suitability for long-term consumption regardless of the patient's age. The aim of this paper is to analyse the potential usability of tea as an element of prophylaxis and pharmacotherapy support in EC patients. The analysis is based on information available from worldwide literature published in the last 15 years.

Quantifying the Effect of Physical Activity on Endometrial Cancer Risk.

Endometrial cancer incidence is rising, with 435,000 global cases in 2019. An effective, low-cost primary prevention strategy is required to reduce disease burden. Obesity, insulin resistance, and inflammation contribute to endometrial carcinogenesis and physical activity targets these pathways. This study sought to quantify the amount of physical activity required to impact upon endometrial cancer risk. Physical activity data from 222,031 female participants with an intact uterus in the UK Biobank study were analyzed using a multivariable Cox proportional hazards model. A systematic review of the literature was performed, searching CENTRAL, Embase, and MEDLINE databases up to April 19, 2021. Studies including participants with and without endometrial cancer investigating the effect of physical activity measured in MET-hours/week (MET-h/week) on disease risk were included. Two reviewers independently selected studies, extracted data, and evaluated the risk of bias. Within the UK Biobank, each 1 MET-h/week increase in total physical activity was associated with a 0.2% [95% confidence interval (CI), 0.1-0.4; P = 0.020] reduction in endometrial cancer risk, equating to a 10.4% reduction if performing 50 MET-h/week or 7 hours of jogging per week. Eleven cohort and 12 case-control studies were identified in the systematic review, including 821,599 participants. One study reported a nonsignificant effect of 1 MET-h/week increases in physical activity on endometrial cancer risk (OR, 1.00; 95% CI, 0.99-1.00). Eight studies found significant reductions in disease risk of 15%-53%, but only in the most physically active individuals. Physical activity reduces endometrial cancer risk, but the effect size appears small. Regular vigorous activity should be encouraged to maximize the health benefit observed. PREVENTION RELEVANCE: Effective, low-cost primary prevention strategies are urgently needed to tackle the rapid global increase in endometrial cancer. We sought to quantify the effect of physical activity on endometrial cancer risk, noting a linear inverse relationship influenced by body mass index. The most beneficial type and amount of activity remain unclear.

Impact of metabolic syndrome on the risk of endometrial cancer and the role of lifestyle in prevention.

Endometrial cancer is the second gynecological cancer with the highest global incidence. Among many associated risk factors, metabolic syndrome is an important and preventable one. It comprises a group of conditions that often occur together: central adiposity, hyperglycemia, arterial hypertension, and atherogenic dyslipidemia. This review aimed to describe the epidemiological and biological relationship between metabolic syndrome and endometrial cancer, focusing on the role of lifestyle in prevention. A literature search was carried out in the PubMed database. 4824 publications were screened, and 123 were included for this review. The association between metabolic syndrome and endometrial cancer has been described. Chronic adipose tissue inflammation and insulin resistance are involved in the development of obesity, particularly visceral adiposity. These changes promote the ideal environment for the development of endometrial cancer. Strategies based on lifestyle modifications may be effective for the prevention of metabolic syndrome and consequently endometrial cancer. Some of these modifications include adopting a diet rich in fruits, vegetables, whole grains, and legumes, depending to the accessibility of these foods for each region. Avoiding ultra-processed foods and increasing daily physical activity were also some suggested modifications. We propose that women be screened for metabolic syndrome to establish early treatment and to possibly prevent endometrial cancer. Clinical trials designed to prove the effect of lifestyle modifications on the prevention of endometrial cancer are needed.

Oral Contraceptive Use in BRCA1 and BRCA2 Mutation Carriers: Absolute Cancer Risks and Benefits.

BACKGROUND: To help BRCA1 and 2 mutation carriers make informed decisions regarding use of combined-type oral contraceptive preparation (COCP), absolute risk-benefit estimates are needed for COCP-associated cancer. METHODS: For a hypothetical cohort of 10 000 women, we calculated the increased or decreased cumulative incidence of COCP-associated (breast, ovarian, endometrial) cancer, examining 18 scenarios with differences in duration and timing of COCP use, uptake of prophylactic surgeries, and menopausal hormone therapy. RESULTS: COCP use initially increased breast cancer risk and decreased ovarian and endometrial cancer risk long term. For 10 000 BRCA1 mutation carriers, 10 years of COCP use from age 20 to 30 years resulted in 66 additional COCP-associated cancer cases by the age of 35 years, in addition to 625 cases expected for never users. By the age of 70 years such COCP use resulted in 907 fewer cancer cases than the expected 9093 cases in never users. Triple-negative breast cancer estimates resulted in 196 additional COCP-associated cases by age 40 years, in addition to the 1454 expected. For 10 000 BRCA2 mutation carriers using COCP from age 20 to 30 years, 80 excess cancer cases were estimated by age 40 years in addition to 651 expected cases; by the age of 70 years, we calculated 382 fewer cases compared with the 6156 cases expected. The long-term benefit of COCP use diminished after risk-reducing bilateral salpingo-oophorectomy followed by menopausal hormone therapy use. CONCLUSION: Although COCP use in BRCA1 and BRCA2 mutation carriers initially increases breast, ovarian, and endometrial cancer risk, it strongly decreases lifetime cancer risk. Risk-reducing bilateral salpingo-oophorectomy and menopausal hormone therapy use appear to counteract the long-term COCP-benefit.

Weight Loss During Intrauterine Progestin Treatment for Obesity-associated Atypical Hyperplasia and Early-Stage Cancer of The Endometrium.

Intrauterine progestin is a treatment option for women with atypical hyperplasia or low-risk endometrial cancer who wish to preserve their fertility, or whose poor surgical fitness precludes safe hysterectomy. We hypothesized that in such women with obesity, weight loss during progestin treatment may improve oncological outcomes. We conducted a prospective nonrandomized study of women with obesity and atypical hyperplasia or low-grade stage 1a endometrial cancer undergoing progestin treatment. Women with a body mass index (BMI) ≥ 35 kg/m2 were offered bariatric surgery; those who declined and those with a BMI of 30 to 34.9 kg/m2 were encouraged to lose weight by low-calorie diet. We assessed uptake of bariatric surgery; weight lost during progestin treatment; and the impact of more than 10% total body weight loss on progestin treatment response at 12 months. 71 women [median age 58 years (interquartile range; IQR 35-65); mean BMI 48 kg/m2 (SD 9.3)] completed the study. Twenty-three women (32%) had bariatric surgery, on average 5 months (IQR 3-8) after progestin treatment commenced. Weight change during progestin treatment was -33.4 kg [95% confidence interval (CI) -42.1, -24.7] and -4.6 kg (95% CI -7.8, -1.4) in women receiving bariatric surgery and low-calorie diet, respectively (P < 0.001). Forty-three women (61%) responded to progestin, while 23 (32%) showed stabilized and 5 (7%) progressive disease. Response at 12 months was not predicted by age or baseline BMI, but women who lost more than 10% of their total body weight were more likely to respond to progestin than those who did not (adjusted odds ratio 3.95; 95% CI 1.3, 12.5; P = 0.02). Thus weight loss may improve oncological outcomes in women with obesity-associated endometrial neoplastic abnormalities treated with progestin. PREVENTION RELEVANCE: This study found that weight loss improves response rates in women with obesity and atypical hyperplasia or low-risk endometrial cancer undergoing conservative management with intrauterine progestin. Given the additional benefits of weight loss for fertility, cardiovascular health and quality of life, future research should focus on how best to accomplish it.

Diabetes Risk Reduction Diet and Endometrial Cancer Risk.

Diabetes increases endometrial cancer risk. We investigated the role of a diabetes risk reduction diet (DRRD) on the risk of endometrial cancer using data from a multicentric, Italian hospital-based case-control study (1992-2006) enrolling 454 histologically confirmed cases of endometrial cancer and 908 controls matched by age and center. We derived a DRRD score assigning higher scores for higher intakes of cereal fiber, fruit, coffee, polyunsaturated:saturated fatty acid ratio, and nuts and for lower glycemic load and lower intakes of red/processed meat and sugar-sweetened beverages/fruit juices. The odds ratios (OR) of endometrial cancer according to the DRRD score were derived by multiple conditional logistic regression models. The OR for high (DRRD score >24, i.e., third tertile) versus medium-low adherence to the DRRD was 0.73 (95% confidence interval, CI, 0.55-0.97). Similar results were observed after the exclusion of diabetic women (OR 0.75; 95% CI, 0.56-1.00) and allowance for total vegetable consumption (OR 0.80; 95% CI, 0.60-1.07). Inverse associations were observed in most of the analyzed subgroups. The OR for high DRRD combined with high vegetable consumption was 0.45 (95% CI, 0.28-0.73). Our results suggest that diets able to reduce diabetes risk may also reduce endometrial cancer risk. High vegetable consumption combined with high adherence to the DRRD may provide additional benefit in endometrial cancer prevention.

The evolving role of targeted metformin administration for the prevention and treatment of endometrial cancer: A systematic review and meta-analysis of randomized controlled trials.

AIM: The aim of the present study was to evaluate the role of metformin in endometrial cancer (EC), focusing on its potential preventive effect in breast cancer and obese patients and its safety and efficacy when added to progesterone monotherapy in EC patients who wish to preserve their fertility. METHODS: We reviewed the literature and then conducted a meta-analysis of the relevant parameters. RESULTS: A total of 6 studies was included in the meta-analysis. Regarding the pre-surgical treatment with metformin versus placebo, meta-analysis of mean difference in Ki-67 after treatment among two groups, revealed no difference (MD -7.10, 95% CI -23.31 to 9.11, p = 0.39). Meta-analysis of fertility sparing EC management with a combination of megestrol acetate (MA) and metformin (500 mg three times a day) in comparison with monotherapy with 160 mg daily MA revealed no difference in either complete response or partial response rates (166 patients OR 2.94, 95% CI 0.85 to 10.15, p = 0.09 and 166 patients OR 0.76, 95% CI 0.34 to 1.66, p = 0.49, respectively). As far as breast cancer survivors under tamoxifen are concerned, metformin was associated with significantly reduced median endometrial thickness after 52 weeks of evaluation compared to women in placebo group (2.3 mm vs 3.0 mm, p = 0.05). CONCLUSIONS: Metformin neither was found to be an anti-proliferative agent against the development of endometrial cancer nor beneficial in addition to the progesterone monotherapy for EC fertility sparing candidates. However, a protective effect of metformin was demonstrated in breast cancer survivors under tamoxifen. Clinical outcomes of the ongoing trials are warranted to evaluate the therapeutic use of metformin in EC.

Should we perform subtotal hysterectomy associated with sacral colpopexy for genital prolapse to prevent the risk of endometrial cancer?

OBJECTIVE: In a menopausal woman scheduled for curative surgery for pelvic organ prolapse (POP) by sacral colpopexy (SC), the question of concomitant hysterectomy is frequently considered by the surgeon. The risk of endometrial cancer (EC) exists in this population, and increases with age and body mass index. The French college of gynecologists and obstetricians (CNGOF) decided to issue good practice guidelines on subtotal hysterectomy (SH) for postmenopausal women scheduled for SC for POP. METHODS: The CNGOF has decided to adopt the AGREE II and GRADE systems for grading scientific evidence. Each recommendation for practice was allocated a grade, which depends on the quality of evidence (QE) (clinical practice guidelines). RESULTS: The prevalence of occult endometrial cancer (EC) found on pathological analysis after SH in this context (concomitant SH associated with SC) is low (<1%) (QE: high). Few studies have assessed the value of preoperative uterine exploration. Performing SH during SC is associated with its own risks, which may diminish the potential "carcinological prevention benefit". Uterine morcellation, performed by laparoscopy or a robot-assisted procedure, is associated with a low risk (<0.6%) of dissemination of an unknown sarcoma/EC (QE: moderate) A risk of dissemination of parasitic myomas (<0.5%) is also possible (QE: moderate). CONCLUSION: It is not recommended to perform a subtotal hysterectomy associated with sacral colpopexy for the sole purpose of reducing the occurrence of endometrial cancer (Recommendation: STRONG [GRADE 1-]; the level of evidence was considered to be low and the risk-benefit balance was considered not to be favorable).

The levonorgestrel intrauterine system for prevention of endometrial cancer in women with obesity: A cost-effectiveness study.

OBJECTIVE: To estimate the cost-effectiveness of the levonorgestrel intrauterine system (LNG-IUS) as an endometrial cancer prevention strategy in women with obesity. METHODS: A Markov decision-analytic model was used to compare 5 strategies in women with a body mass index of 30 or greater: 1) Usual care 2) LNG-IUS for 5 years 3) LNG-IUS for 7 years 4) LNG-IUS for 5 years, replaced once for a total of 10 years 5) LNG-IUS for 7 years, replaced once for a total of 14 years. Obesity was presumed to be associated with a 3-fold relative risk of endometrial cancer incidence and a 2.65-fold disease-specific mortality. The LNG-IUS was assumed to confer a 50% reduction in cancer incidence over the period of the LNG-IUS insertion. Outcomes were incremental cost-effectiveness ratios, calculated in 2019 Canadian dollars (CAD) per year of life saved. One-way and two-way sensitivity analyses were performed. RESULTS: The LNG-IUS strategy was considered cost-effective if the cost of the intervention is less than $66,400 CAD ($50,000 US dollars) per year of life saved. The strategy becomes cost-effective if the LNG-IUS is inserted at age 57 (strategy #2), at age 52 for strategy #3, at age 51 for strategy #4 and at age 45 for strategy #5, when compared to usual care. The results are stable to variations in cost but sensitive to the estimated risk reduction of the LNG-IUS and the impact of obesity on endometrial cancer incidence and disease-specific mortality. CONCLUSION: The LNG-IUS is a cost-effective method of endometrial cancer prevention in women with obesity.