Abstract In 1983 Jan V. Bokhman, M.D. published a landmark paper entitled “Two Pathogenetic Types of Endometrial Carcinoma” in which an enduring dualistic view of endometrial cancer was first ...proposed. “Type I” cancers are thought to represent estrogen driven mostly low grade endometrioid tumors strongly associated with obesity and other components of the metabolic syndrome. “Type II” cancers represent higher grade non-endometrioid tumors for which the latter associations are less significant. Basic tenets of this dichotomy including significant prognostic differences have been abundantly confirmed by later literature. The construct has in turn contributed a useful framework for decades of teaching and scientific advancement across disciplines. However, recent large epidemiologic studies indicate a more complex web of risk factors with obesity and hormones likely playing an important role across the entire endometrial cancer histologic and clinical spectrum. Moreover, high quality molecular data and refinements in pathologic classification challenge any simplistic classification of endometrial cancer. For example, the Cancer Genome Atlas (TCGA) recently defined four clinically distinct endometrial cancer types based on their overall mutational burden, specific p53, POLE and PTEN mutations, microsatellite instability and histology. Additionally, new histologic categories with clear prognostic implications have been accepted and it is becoming evident from an epidemiologic point of view that metabolic factors may play an important role in endometrial cancer overall. While Bokhman's intuitive dualistic model remains relevant when working with large registries and databases lacking granular information; most other efforts should integrate clinical, pathological and molecular specifics into more nuanced classifications.
Differences in receipt of guideline-concordant treatment might underlie well-established racial disparities in endometrial cancer mortality.
Using the National Cancer Database, we assessed the ...hypothesis that among women with endometrioid endometrial cancer, racial/ethnic minority women would have lower odds of receiving guideline-concordant treatment than white women. In addition, we hypothesized that lack of guideline-concordant treatment was linked with worse survival.
We defined receipt of guideline-concordant treatment using the National Comprehensive Cancer Network guidelines. Multivariable logistic regression models were used to compute odds ratios and 95% confidence intervals for associations between race and guideline-concordant treatment. We used multivariable Cox proportional hazards regression models to estimate hazards ratios and 95% confidence intervals for relationships between guideline-concordant treatment and overall survival in the overall study population and stratified by race/ethnicity.
This analysis was restricted to the 89,319 women diagnosed with an invasive, endometrioid endometrial cancer between 2004 and 2014. Overall, 74.7% of the cohort received guideline-concordant treatment (n = 66,699). Analyses stratified by race showed that 75.3% of non-Hispanic white (n = 57,442), 70.1% of non-Hispanic black (n = 4334), 71.0% of Hispanic (n = 3263), and 72.5% of Asian/Pacific Islander patients (n = 1660) received treatment in concordance with guidelines. In multivariable-adjusted models, non-Hispanic black (odds ratio, 0.92, 95% confidence interval, 0.86–0.98) and Hispanic women (odds ratio, 0.90, 95% confidence internal, 0.83–0.97) had lower odds of receiving guideline-concordant treatment compared with non-Hispanic white women, while Asian/Pacific Islander women had a higher odds of receiving guideline-concordant treatment (odds ratio, 1.11, 95% confidence interval, 1.00–1.23). Lack of guideline-concordant treatment was associated with lower overall survival in the overall study population (hazard ratio, 1.12, 95% confidence interval, 1.08–1.15) but was not significantly associated with overall survival among non-Hispanic black (hazard ratio, 1.09, 95% confidence interval, 0.98–1.21), Hispanic (hazard ratio, 0.92, 95% confidence interval=0.78–1.09), or Asian/Pacific Islander (hazard ratio, 0.90, 95% confidence interval, 0.70–1.16) women.
Non-Hispanic black and Hispanic women were less likely than non-Hispanic white women to receive guideline-concordant treatment, while Asian/Pacific Islander women more commonly received treatment in line with guidelines. Furthermore, in the overall study population, overall survival was worse among those not receiving guideline-concordant treatment, although low power may have had an impact on the race-stratified models. Future studies should evaluate reasons underlying disparate endometrial cancer treatment.
Cancer survivors have a higher risk of developing and dying from cardiovascular disease (CVD) compared to the general population. We sought to determine whether 10-year risk of atherosclerotic CVD ...(ASCVD) is elevated among those with vs. without a cancer history in a nationally representative U.S. sample.
Participants aged 40-79 years with no CVD history were included from the 2007-2016 National Health and Nutrition Examination Survey. Cancer history was self-reported and 10-year risk of ASCVD was estimated using Pooled Cohort Equations. We used logistic regression to estimate associations between cancer history and odds of elevated (≥7.5%) vs. low (<7.5%) 10-year ASCVD risk. An interaction between age and cancer history was examined.
A total of 15,095 participants were included (mean age = 55.2 years) with 12.3% (n = 1,604) reporting a cancer history. Individuals with vs. without a cancer history had increased odds of elevated 10-year ASCVD risk (OR = 3.42, 95% CI: 2.51-4.66). Specifically, those with bladder/kidney, prostate, colorectal, lung, melanoma, or testicular cancer had a 2.72-10.47 higher odds of elevated 10-year ASCVD risk. Additionally, age was an effect modifier: a cancer history was associated with 1.24 (95% CI: 1.19-4.21) times higher odds of elevated 10-year ASCVD risk among those aged 60-69, but not with other age groups.
Adults with a history of self-reported cancer had higher 10-year ASCVD risk. ASCVD risk assessment and clinical surveillance of cardiovascular health following a cancer diagnosis could potentially reduce disease burden and prolong survival, especially for patients with specific cancers and high ASCVD risk.
•Endometrial cancer risk is substantially increased among users of unopposed estrogens, with further enhancements among thin women.•The addition of progestins for >25 days/month reduces risk, to ...levels even somewhat lower than that of non-hormone users.•Users of progestins for <10 days/month remain at an elevated risk.
Endometrial cancer is clearly a hormonally responsive tumor, with a critical role played by estrogens unopposed by progestins. Numerous epidemiologic studies have shown substantial risk increases associated with use of unopposed estrogens, especially among thin women. This risk, however, can be reduced if progestins are added to the therapy. The manner in which progestins are prescribed is a critical determinant of risk. Most studies show that women who have ever used progestins continuously (>25 days/months) are at somewhat reduced risk relative to non-users (meta-analysis relative risk, RR, based on observational studies=0.78, 95 confidence intervals, CI, 0.72–0.86). The reduced risk in greatest among heavy women. In contrast, women who have ever used progestins sequentially for <10 days each month are at increased risk, with meta-analysis results showing on overall RR of 1.76 (1.51–2.05); in contrast, progestins given for 10–24 days/month appear unrelated to risk (RR=1.07, 0.92–1.24). These risks were based on varying patterns of usage, with little information available regarding how endometrial cancer risk is affected by duration of use, type and/or dose of estrogen or progestin, or mode of administration. Effects may also vary by clinical characteristics (e.g., differences for Type I vs. II tumors). Further resolution of many of these relationships may be dependent on pooling data from multiple studies to derive sufficient power for subgroups of users. With changing clinical practices, it will be important for future studies to monitor a wide range of exposures and to account for divergent effects of different usage patterns.
This article is part of a Special Issue entitled ‘Menopause’.
Weight loss through lifestyle modification can produce health benefits and may reduce cancer risk. The goal of this study was to examine the feasibility of and adherence to a 15-week telephone-based ...weight loss intervention in rural Ohio, an area with high rates of obesity.
This pilot 2-arm randomized controlled study was designed for rural Ohio residents who were overweight or obese. Eligible participants were 2:1 randomly assigned to either a 15-week weight loss intervention group or active control group. The weight loss intervention group received weekly telephone sessions to improve healthy diet and increase physical activity. The active control group received education brochures with information on physical activity and dietary guidelines. Feasibility was defined as at least 80% of participants completing the follow-up surveys, and acceptable adherence was defined as the percentage of participants in the weight loss group who attend ≥75% of weekly telephone sessions.
A total of 423 individuals entered the online screening survey, 215 (50.8%) completed the survey, and 98 (45.6%) of those were eligible. Forty eligible individuals were enrolled and randomly assigned to the weight loss group (n = 27) or active control group (n = 13). The average age of the weight loss group was 49 (SD = 10) years, and 89% were female. The average age of the active control group was 51 (SD = 9) years, and 92% were female. Feasibility was demonstrated: 90% of participants completed the online follow-up surveys at 15-weeks. Among participants in the weight loss group, 22 out of 27 (81.5%) completed the 15-week intervention, the average number of sessions attended was 9.7 (64.9%). Adherence to the intervention was rated as acceptable among almost half of the group (48.1%).
Feasibility of a 15-week telephone-based weight loss study among rural residents with overweight/obesity were determined. A future study will test this intervention for weight loss efficacy.
Women with endometrial cancer (EC) are the second largest population of female cancer survivors in the United States. However, the outcomes of EC survivors, from the patient perspective, are not ...well-understood. Therefore, we conducted a systematic review of patient-reported outcomes (PROs) following an EC diagnosis.
We searched MEDLINE, EMBASE, Scopus, CINAHL, and reference lists to identify published observational studies that examined PROs among women with EC. Reviewers independently reviewed eligible full-text study articles and conducted data extraction. We qualitatively summarized included articles according to exposures e.g. body mass index (BMI), treatment, etc. or specific PROs (e.g. sexual function).
Of 1722 unique studies, 102 full-text articles were reviewed, of which a total of 27 studies fulfilled the inclusion criteria. The most commonly used PRO questionnaires were the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) (n=9), Short Form 36 Questionnaire (SF-36, n=8), the Functional Assessment of Cancer Therapy-General (FACT-G, n=5), and the Female Sexual Function Index (FSFI, n=4). Obesity was associated with lower quality of life (QOL) and physical functioning. Treatment type affected several outcomes. Laparoscopy generally resulted in better QOL outcomes than laparotomy. Likewise, vaginal brachytherapy was associated with better outcomes compared to external beam radiation. Sexual function outcomes were dependent on age, time since diagnosis, and having consulted a physician before engaging in sexual activities. In addition, a physical activity intervention was associated with improved sexual interest but not sexual function.
Our review provides insight into the experience of EC survivors from the patient perspective. Factors that contribute to QOL, such as pain, fatigue, emotional and social functioning, should be monitored following an EC diagnosis.
•PROs among EC survivors are not well understood.•A range of PRO questionnaires were used and timing of the questionnaire varied.•Patient characteristics, such as higher weight, were associated with worse PROs.•PROs should be monitored following an EC diagnosis.
Among women diagnosed with non-endometrioid endometrial carcinoma (EC), we investigated associations between race/ethnicity and receipt of guideline-concordant treatment (GCT), as well as ...relationships between GCT and survival.
We used the National Cancer Database and identified 21,177 non-Hispanic White (NHW), 6657 non-Hispanic Black (NHB), 1689 Hispanic, and 903 Asian/Pacific Islander (AS/PI) women diagnosed with non-endometrioid EC between 2004 and 2014. Year-specific National Comprehensive Cancer Network (NCCN) guidelines were used to classify GCT. We used multivariable logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for associations between race/ethnicity and GCT receipt. Multivariable-adjusted Cox proportional hazards models were used to estimate hazards ratios (HRs) and 95% CIs for relationships between GCT and overall survival in the total study population and stratified by race/ethnicity.
Overall, 43.8% of women with non-endometrioid EC received GCT. Compared to NHW women, NHB (OR = 1.01, 95% CI = 0.95–1.07), Hispanic (OR = 1.01, 95% CI = 0.91–1.12) and AS/PI women (OR = 1.10, 95% CI = 0.96–1.26) did not have significantly different odds of receiving GCT. GCT was significantly associated with improved survival among NHW (HR = 0.84, 95% CI = 0.80–0.87), NHB (HR = 0.85, 95% CI = 0.80–0.91), and Hispanic women (HR = 0.84, 95% CI = 0.72–0.98) but not among AS/PI women (HR = 0.97, 95% CI = 0.78–1.19).
While more than half of women with non-endometrioid EC did not receive GCT, no difference in GCT receipt by race/ethnicity was observed. When received, GCT was associated with improved survival in almost all racial groups. Interventions to improve GCT adherence may improve survival for most women with non-endometrioid EC.
•Over half of women with non-endometrioid endometrial cancer do not receive guideline-concordant treatment.•Rates of guideline-concordant treatment in non-endometrioid endometrial cancer do not differ by race.•Guideline-concordant treatment adherence interventions may improve survival.•Research is needed into barriers to adherence to treatment guidelines.
Purpose Although obesity is an established endometrial cancer risk factor, information about the influence of weight loss on endometrial cancer risk in postmenopausal women is limited. Therefore, we ...evaluated associations among weight change by intentionality with endometrial cancer in the Women's Health Initiative (WHI) observational study. Patients and Methods Postmenopausal women (N = 36,794) ages 50 to 79 years at WHI enrollment had their body weights measured and body mass indices calculated at baseline and at year 3. Weight change during that period was categorized as follows: stable (change within ± 5%), loss (change ≥ 5%), and gain (change ≥ 5%). Weight loss intentionality was assessed via self-report at year 3; change was characterized as intentional or unintentional. During the subsequent 11.4 years (mean) of follow-up, 566 incident endometrial cancer occurrences were confirmed by medical record review. Multivariable Cox proportional hazards regression models were used to evaluate relationships (hazard ratios HRs and 95% CIs) between weight change and endometrial cancer incidence. Results In multivariable analyses, compared with women who had stable weight (± 5%), women with weight loss had a significantly lower endometrial cancer risk (HR, 0.71; 95% CI, 0.54 to 0.95). The association was strongest among obese women with intentional weight loss (HR, 0.44; 95% CI, 0.25 to 0.78). Weight gain (≥ 10 pounds) was associated with a higher endometrial cancer risk than was stable weight, especially among women who had never used hormones. Conclusion Intentional weight loss in postmenopausal women is associated with a lower endometrial cancer risk, especially among women with obesity. These findings should motivate programs for weight loss in obese postmenopausal women.
PDF
