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.

Hysterectomy Versus Hysteropexy at the Time of Native Tissue Pelvic Organ Prolapse Repair: A Cost-Effectiveness Analysis.

OBJECTIVE: The aim of the study was to determine whether a hysterectomy at the time of native tissue pelvic organ prolapse repair is cost-effective for the prevention of endometrial cancer. METHODS: We created a decision analysis model using TreeAge Pro. We modeled prolapse recurrence after total vaginal hysterectomy with uterosacral ligament suspension (TVH-USLS) versus sacrospinous ligament fixation hysteropexy (SSLF-HPXY). We modeled incidence and diagnostic evaluation of postmenopausal bleeding, including risk of endometrial pathology and diagnosis or death from endometrial cancer. Modeled costs included those associated with the index procedure, subsequent prolapse repair, endometrial biopsy, pelvic ultrasound, hysteroscopy, dilation and curettage, and treatment of endometrial cancer. RESULTS: TVH-USLS costs US $587.61 more than SSLF-HPXY per case of prolapse. TVH-USLS prevents 1.1% of women from experiencing postmenopausal bleeding and its diagnostic workup. It prevents 0.95% of women from undergoing subsequent major surgery for the treatment of either prolapse recurrence or suspected endometrial cancer. Using our model, it costs US $2,698,677 to prevent one cancer death by performing TVH-USLS. As this is lower than the value of a statistical life, it is cost-effective to perform TVH-USLS for cancer prevention. Multiple 1-way sensitivity analyses showed that changes to input variables would not significantly change outcomes. CONCLUSIONS: TVH-USLS increased costs but reduced postmenopausal bleeding and subsequent major surgery compared with SSLF-HPXY. Accounting for these differences, TVH-USLS was a cost-effective approach for the prevention of endometrial cancer. Uterine preservation/removal at the time of prolapse repair should be based on the woman's history and treatment priorities, but cancer prevention should be one aspect of this decision.

Diabetic Pharmacotherapy and Endometrial Cancer Risk Within a Publicly Funded Health Care System.

OBJECTIVE: There is conflicting evidence regarding the association between metformin and endometrial cancer risk. The objective of this study was to evaluate the association between type of diabetic pharmacotherapy and endometrial cancer risk within a population-based study. The hypothesis was that metformin was associated with the lowest risk. METHODS: This was a nested case-control study using data from the BC Cancer Registry (2000-2009) and from a province-wide prescription network (PharmaNet) since 1996. Patients were classified by drug exposure (metformin, thiazolidinediones, secretagogues, with or without insulin). The primary analysis was a conditional logistic regression to estimate the odds ratios for endometrial cancer in the drug exposure groups. Sensitivity analysis was carried out to account for uncertainty regarding various parameters. The secondary analysis evaluated the effect of dosage using a principal components analysis. RESULTS: The study cohort comprised 492 cases and 4404 controls. The primary analysis revealed no difference in endometrial cancer risk between those using metformin and those prescribed other classes of medications (OR 1.5, 95% CI 0.9 to 2.4). Women receiving all classes of medications had almost a two-fold increase in risk (OR 1.9, 95% CI 1.1 to 3.3). The secondary analysis revealed an increased risk associated with a greater duration of treatment and number of prescriptions (OR 1.3, 95% CI 1.2 to 1.4). CONCLUSION: In this population-based study, metformin was not associated with a decreased endometrial cancer risk. Women receiving multiple types of medications over a long time had the highest risk, implying that the extent of insulin resistance, rather than the effect of any specific medication, drives endometrial cancer risk.

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

Already the fourth most common cancer in women in the developed world, the incidence of endometrial cancer is increasing rapidly, in line with the increasing prevalence of obesity. Relatively few studies have been undertaken of risk-reducing interventions aimed at limiting the impact of the disease on both individuals and the health service. Those that have been performed have demonstrated only modest results due to their application in relatively unselected populations. A validated risk prediction model is therefore urgently required to identify individuals at particularly high risk of endometrial cancer who may benefit from targeted primary prevention strategies and to guide trial eligibility. On the basis of a systematic review of the literature, the evidence for inclusion of measures of obesity, reproduction, insulin resistance, and genetic risk in such a model is discussed, and the strength of association between these risk factors and endometrial cancer is used to guide the development of a pragmatic risk prediction scoring system that could be implemented in the general population. Provisional cutoff values are described pending refinement of the model and external validation in large prospective cohorts. Potential risk-reducing interventions are suggested, highlighting the need for future studies in this area if the increasing tide of endometrial cancer is to be stemmed. Cancer Prev Res; 10(1); 1-13. ©2016 AACR.

Levonorgestrel Intrauterine Device as an Endometrial Cancer Prevention Strategy in Obese Women: A Cost-Effectiveness Analysis.

OBJECTIVE: To estimate the cost-effectiveness of the levonorgestrel intrauterine device (IUD) as an endometrial cancer prevention strategy in obese women. METHODS: A modified Markov model was used to compare IUD placement at age 50 with usual care among women with a body mass index (BMI, kg/m) 40 or greater or BMI 30 or greater. The effects of obesity on incidence and survival were incorporated. The IUD was assumed to confer a 50% reduction in cancer incidence over 5 years. Costs of IUD and cancer care were included. Clinical outcomes were cancer diagnosis and deaths from cancer. Incremental cost-effectiveness ratios were calculated in 2015 U.S. dollars per year of life saved. One-way and two-way sensitivity analyses and Monte Carlo probabilistic analyses were performed. RESULTS: For a 50 year old with BMI 40 or greater, the IUD strategy is costlier and more effective than usual care with an incremental cost-effectiveness ratio of $74,707 per year of life saved. If the protective effect of the levonorgestrel IUD is assumed to be 10 years, the incremental cost-effectiveness ratio decreases to $37,858 per year of life saved. In sensitivity analysis, a levonorgestrel IUD that reduces cancer incidence by at least 68% in women with BMIs of 40 or greater or costs less than $500 is potentially cost-effective. For BMI 30 or greater, the incremental cost-effectiveness ratio of IUD strategy is $137,223 per year of life saved compared with usual care. In Monte Carlo analysis, IUD placement for BMI 40 or greater is cost-effective in 50% of simulations at a willingness-to-pay threshold of $100,000 per year of life saved. CONCLUSION: The levonorgestrel IUD is a potentially cost-effective strategy for prevention of deaths from endometrial cancer in obese women.

A Structured Assessment to Decrease the Amount of Inconclusive Endometrial Biopsies in Women with Postmenopausal Bleeding.

OBJECTIVE: To determine whether structured assessment of outpatient endometrial biopsies decreases the number of inconclusive samples. DESIGN: Retrospective cohort study. SETTING: Single hospital pathology laboratory. POPULATION: Endometrial biopsy samples of 66 women with postmenopausal bleeding, collected during the usual diagnostic work-up and assessed as insufficient for a reliable histological diagnosis. METHODS: Endometrial biopsy samples were requested from the pathology laboratories. The retrieved samples were systematically reassessed by a single pathologist specialized in gynecology. MAIN OUTCOME MEASURE: Disagreement between initial assessment and conclusion after structured reassessment. RESULTS: We retrieved 36 of 66 endometrial biopsy samples from six different pathology laboratories. Structured reassessment of the retrieved samples by a single pathologist specialized in gynecology did not change the conclusion in 35 of the 36 samples. The remaining sample contained a large amount of endometrial tissue and the diagnosis at reassessment was endometrial hyperplasia without atypia. All other samples contained insufficient material for a reliable diagnosis. CONCLUSION: A structured reassessment of endometrial biopsies samples, which were classified as inconclusive due to insufficient material, did not change the conclusion. Although it might be helpful for pathologists to have diagnostic criteria for adequacy and/or inadequacy of an endometrial biopsy sample, the gain in efficiency is likely to be small.

Genetic counseling and cascade genetic testing in Lynch syndrome.

Lynch syndrome is the most common cause of inherited colorectal and endometrial cancers. Individuals with Lynch syndrome have a 10-80 % lifetime risk for colorectal cancer and a 15-60 % lifetime risk for endometrial cancer. Both cancers are preventable through chemoprevention, intensive cancer surveillance, and risk-reducing surgery options. Efforts to identify as many individuals with Lynch syndrome as possible will prevent cancers and save lives. This includes the traditional cancer genetic counseling model whereby individuals with and without cancer are evaluated for a possible Lynch syndrome diagnosis based on their personal and family history of colon polyps and cancers. It also includes universal tumor screening for Lynch syndrome whereby all individuals with colorectal or endometrial cancer are screened for tumor features of Lynch syndrome at the time of diagnosis. Those with tumors suspicious for Lynch syndrome are referred for cancer genetic counseling regardless of their family history of cancer. This two approaches must be maximized to attain high patient reach. Finally, and perhaps most importantly, cascade testing among the at-risk relatives of those diagnosed with Lynch syndrome is critically important to maximize the diagnosis of individuals with Lynch syndrome. In fact, the cost-effectiveness of universal tumor screening for Lynch syndrome relies entirely on counseling and testing as many at-risk individuals as possible since young unaffected individuals stand to benefit the most from an early diagnosis of Lynch syndrome. This approach must be optimized to achieve high family reach. It will take a concerted effort from patients, clinicians and public health officials to improve current approaches to the diagnosis of Lynch syndrome and the prevention and treatment of Lynch syndrome-associated cancer but these lessons can be applied to other conditions as the ultimate example of personalized medicine.

Hysterectomy at the time of colpocleisis: a decision analysis.

INTRODUCTION AND HYPOTHESIS: Colpocleisis is an obliterative procedure for the treatment of pelvic organ prolapse (POP) with success rates nearing 100 %. Concomitant hysterectomy is commonly performed to avoid potential difficulty or delay in diagnosis and management of endometrial cancer (EMC). The objective was to assess the utility of vaginal hysterectomy at the time of a colpocleisis using decision analysis. METHODS: A decision analysis model was constructed to compare the outcomes of Le Fort colpocleisis (C) with those of colpocleisis and concomitant vaginal hysterectomy (CH). Probability and utility values from published data and expert opinions were utilized. As EMC risk changes with age, the total expected utility for each alternative was calculated for each decade using the rollback method. Sensitivity analysis was performed using Monte Carlo simulation. When evaluating specifically the risk of developing EMC in those patients with uterine conservation (C) and the risk of laparotomy in patients undergoing CH, one-way sensitivity analysis was used to determine a threshold for decision reversal. Two-way sensitivity analysis determined a threshold for complications common to both C and CH. RESULTS: The expected overall utility for C was higher than for CH for all ages 30-90 years. This difference was statistically significant for ages 40-90, favoring C. The Monte Carlo simulation results confirmed that the difference between the two alternatives was statistically significant. Multiple one-way sensitivity analyses confirmed model robustness. CONCLUSIONS: Colpocleisis should be preferred to CH. Concomitant hysterectomy commonly performed for cancer may be justified in patients younger than 40 years of age.

Assessment of Breast Cancer Patients' Knowledge and Decisional Conflict Regarding Tamoxifen Use.

Breast cancer is the most common type of female cancer. Tamoxifen, a selective estrogen receptor modulator, is widely used to decrease breast cancer recurrence and mortality among patients. However, it also increases the risk of endometrial cancer. This study aimed to assess knowledge and decisional conflict regarding tamoxifen use. Between June and October 2014, breast cancer patients using tamoxifen were consecutively screened and requested to complete a survey including the EQ-5D, Satisfaction with Decision Scale (SWD), Decisional Conflict Scale (DCS), and a self-developed, 15-item questionnaire measuring tamoxifen-related knowledge. The study sample comprised 299 patients. The mean total knowledge score was 63.4 of a possible 100.0 (range, 13.3-93.3). While 73.9% of the participants knew that tamoxifen reduces the risk of breast cancer recurrence, only 57.9% knew that the drug increases endometrial cancer risk. A higher education level (≥ college) was associated with a higher, total knowledge score (ß = 4.291; P = 0.017). A higher knowledge score was associated with a decreased DCS score (ß = -0.366; P < 0.001). A higher SWD score was also associated with decreased decisional conflict (ß = -0.178; P < 0.001). In conclusion, the breast cancer patients with higher levels of tamoxifen-related knowledge showed lower levels of decisional conflict regarding tamoxifen use. Clinicians should provide the exact information about tamoxifen treatment to patients, based on knowledge assessment results, so as to aid patients' decision-making with minimal conflict.

Avaliação endometrial em pacientes usuárias de tamoxifeno / Endometrial assessment in patients taking tamoxifen

O câncer de mama é a neoplasia maligna mais frequente em mulheres tanto no Brasil quanto no mundo. A doença é mais comum acima dos 50 anos, coincidindo com a faixa etária de risco para o câncer de endométrio. O tamoxifeno é um modulador seletivo de receptor de estrogênio (SERMs), usadona terapêutica das mulheres portadoras de câncer de mama. Assim como os outros SERMs (raloxifeno,toremifeno,arzoxifeno e lasoxifeno), o tamoxifeno pode atuar como antagonista ou agonista, dependendo do tecido-alvo.Nestas pacientes, o uso destes agonistas seletivos embora apresente maior benefício do que risco para o tratamento do câncer de mama, pode causar efeitos secundários no endométrio, com aumento do risco para doenças malignas. Consensos atuais, porém, não demonstram benefício de nenhum método de rastreio para câncer endometrial de rotina. O que se recomenda, nas pacientes na pré e pós-menopausa com câncer de mama, é o exame ginecológico com intervalo anual e o prosseguimento com propedêutica, através de biópsia do endométrio nas pacientes pós-menopausa que apresentam sangramento vaginal.(AU)

Breast cancer is the most common malignancy in women both in Brazil and in the world. The disease is more common over 50 years, coinciding with the age of risk for endometrial cancer. Tamoxifen is a selective modulator of estrogen receptor (SERMs) used in the treatment of women with breast cancer. Like other SERMs (raloxifene, toremifene, arzoxifeno and lasoxifeno), tamoxifen may act as antagonist or agonist depending on the target tissue. In these patients, although showing greater benefit of what risk for the treatment of the breast cancer, can cause side effects on the endometrium, with increased risk for malignant diseases. Current consensus, however, do not demonstrate any benefit from routine screening method for endometrial cancer. Women with breast cancer should undergo annual gynecologic examinations for premenopausal and postmenopausal patients and further workup by means of biopsy in patients with postmenopausal vaginal bleeding.(AU)

Assessment of transvaginal sonography combined with endometrial cytology as a mass screening method for endometrial cancer in Beijing.

This was a two-phase, large sample-group study assessing the effectiveness of combined transvaginal sonography (TVS) and endometrial cytology in endometrial cancer screening. In phase one, 3308 women without known cancer were enrolled and TVS was performed on those with symptoms or endometrial cancer risk factors. Endometrial cytology was carried out on post-menopausal women with endometrial thickness >or= 5 mm and on pre-menopausal women with endometrial thickness >or= 10 mm. Dilation and curettage (D & C) was performed if cytological findings were inconclusive, or indicated cancer or pre-cancer. The mass screening safety interval is at least 2 years and phase two was carried out 2 years after phase one, using the same procedures, on the 3305 women who were originally found to be cancer free. Combined TVS and endometrial cytology resulted in 100% sensitivity and 99.0% specificity, reducing unnecessary D & C by 91.7% and screening costs by 20.1%. Combined TVS examination and endometrial cytology decreased potentially harmful examinations, patient suffering and medical costs, and is worth considering for broad implementation.

Cost-effectiveness analysis of endometrial cancer prevention strategies for obese women.

OBJECTIVE: It is unknown whether obese women would benefit from oral contraceptives or screening as endometrial cancer prevention strategies. We estimated the net health benefits and cost-effectiveness of these strategies in a hypothetical cohort of obese women. METHODS: A Markov decision-analytic model evaluated 4 strategies: 1) no prevention (reference strategy); 2) oral contraceptive pills (OCPs) for 5 years; 3) annual screening with endometrial biopsy from age 30; 4) biennial screening from age 30. Net health benefit was life expectancy and primary outcome was the incremental cost-effectiveness ratio. Baseline and transition probabilities were obtained from published literature and the Surveillance Epidemiology and End Results database, and costs were from the U.S. Department of Health and Human Services and Agency for Healthcare Research and Quality. Sensitivity analyses were performed for uncertainty around various measures. RESULTS: Average life expectancy for all strategies ranged from 74.52 to 74.60 years. None of the strategies had an incremental cost-effectiveness ratio less than $50,000 per year of life saved relative to the next best strategy. Endometrial cancer risk in obese women had to be 13 times greater than the general population risk before OCPs were a cost-effective intervention. CONCLUSION: Oral contraceptives and current screening methods are not cost-effective endometrial cancer prevention strategies for obese women. Risk factors such as morbid obesity and longstanding anovulation may define a subgroup at highest risk of endometrial cancer for whom OCPs may be a cost-effective strategy. Interventions that reduce endometrial cancer risk further or those with additional health benefits are needed in this population. LEVEL OF EVIDENCE: III.

Should menopausal women at increased risk for breast cancer use tamoxifen, raloxifene, or hormone therapy?: a framework for personalized risk assessment and counseling.

BACKGROUND: Menopausal women with a family history of breast cancer have several treatment options, including tamoxifen, raloxifene, and hormone therapy. This complex decision should be based on each woman's risk to develop breast cancer, menopausal symptoms, preferences, and risks for other conditions. Current models in use do not include pedigree analysis, personalized risk assessment, or genetic testing in this process. METHODS: We created a personalized risk assessment and genetic counseling intervention for healthy women with a first-degree relative with breast cancer. Participants were given a personalized risk assessment for breast cancer, heart disease, osteoporosis, and uterine cancer based on family history and personal health data. COUNSELING MODEL: The effectiveness of this novel genetic counseling intervention was demonstrated in a randomized trial and these results are published elsewhere. The framework for this counseling model, with case examples from the clinical trial, is outlined in this article. CONCLUSIONS: As more menopausal therapies are developed, each with its own risks and benefits, it will become even more critical to have a personalized counseling model for use in this process. Clinicians and educators can utilize the framework presented here for counseling women with a family history of breast cancer.

Physical activity and endometrial cancer risk: a review of the current evidence, biologic mechanisms and the quality of physical activity assessment methods.

OBJECTIVES: To (1) determine the nature of the association between physical activity and endometrial cancer risk; (2) assess the contribution of variation in the quality of physical activity measurement to inconsistencies in study results; and (3) review the biologic mechanisms that might mediate possible effects of physical activity on risk. METHODS: We reviewed and summarized all published epidemiologic studies examining physical activity and endometrial cancer risk, and evidence relating to possible biologic mechanisms. We assigned each study a quality score for physical activity measurement. RESULTS: Fourteen of the 18 studies showed a convincing or possible protective effect of physical activity on endometrial cancer risk, with an average relative risk reduction of around 30%. A dose-response relation was observed in 7 of 13 studies. The quality score was not related to the observed strength of association or the presence of a dose-response relation. There was epidemiologic and biologic evidence that vigorous activity, as well as light and moderate intensity activities, such as housework, gardening or walking for transportation, may reduce risk. CONCLUSIONS: Physical activity probably has a protective role in endometrial cancer development. More epidemiologic and biologic evidence is needed to make conclusive recommendations on optimal types, characteristics or time periods of physical activity.

Dietary factors and endometrial cancer risk. Results of a case-control study in Mexico.

Daily diet factors that could potentially be related to endometrial cancer (EC) in Mexico are still unknown. This study aims to evaluate the association between EC and Mexican dietary factors. A case-control study in Mexico City was conducted during 1995-1997 in a social security hospital, using 85 incident cases of EC and 629 controls. A validated questionnaire with 116 items about the frequency and type of food intake was used. The analysis of nutrients was performed using the residual method, adjusting by predictor variables through logistic regression methods. In addition, partitional models estimated total caloric intake for other sources. We found no association between EC risk and consumption of animal or vegetable proteins, saturated, monounsaturated, or polyunsaturated fat, although high intake of nutrients such as lactose (odds ratio [OR], 0.46; 95% confidence interval [CI], 0.21-1.01, P for trend = 0.004), vitamin D (OR, 0.38; 95% CI, 0.18-0.82, P= 0.003), and calcium (OR, 0.39; 95% CI, 0.17-0.89, P= 0.02) were inversely associated with EC. Our results suggest that dietary vitamin D and calcium play an important role in the development of EC, although the mechanisms postulated should be explained with additional studies with large populations.

[Essential to discover hereditary colorectal and endometrial cancer. Mutations in "HNPCC individuals" can cause several different tumors]. / Viktigt att upptäcka ärftliga fall av kolorektal- och endometriecancer. Mutationer hos "HNPCC-individer" kan orsaka flera tumörsjukdomar.

Hereditary Nonpolyposis Colorectal Cancer (HNPCC) is one of our most common hereditary cancer syndromes and confers an increased risk for several tumor types, with the greatest lifetime risks being for colorectal cancer and endometrial cancer. Hereditary mutations in one of several mismatch-repair (MMR) genes cause the syndrome, and 39 such mutations, involving the genes MLH1, MSH2 and MSH6, have been been characterized in Sweden. Screening programs for HNPCC have been shown to be cost-effective and to prevent cancer. Identification of HNPCC individuals thus allows prevention of additional tumors in the patient as well as in the family.