Enhancing engagement in biobanking research among Black women with endometrial cancer.

BackgroundIn cancer, lack of social support is associated with reduced survival. Peer support interventions have reduced social isolation among Black women with cancer but have yet to be adapted for Black people diagnosed with endometrial cancer – a growing, high-need demographic that has been historically excluded from community-engaged research. Our research team at the University of Washington addressed this gap by working within an established community partnership to develop a pragmatic randomized controlled trial to adapt and test social support interventions among Black women with EC – the Social Interventions for Support during Treatment of Endometrial Cancer and Recurrence (SISTER) Study. The goal of this commentary is to describe the stakeholder engagement practices used in the conceptualization and start-up of the SISTER Study.Main TextThe research team, including Black endometrial cancer survivors, developed a grant proposal, grounded in engagement values derived from the Patient-Centered Outcomes Research Institute® and the Public Health Critical Race Praxis. The team implemented values-aligned stakeholder engagement activities, including the creation of an advisory board charter, structuring meetings and roles, incorporating stakeholder input into study material and protocols, establishing an external advisory board, and developing an engagement evaluation plan. Overall, we learned that it is possible to design and operationalize a community-engaged pragmatic randomized controlled trial in alignment with a racial equity social justice research methodology and patient-centered outcomes research engagement practices. We describe other lessons learned, including operational challenges to implementing our engagement practices and our approaches to addressing these challenges, and promising practices to replicate in future studies or partnerships.ConclusionThe SISTER Study is an example of establishing principled methods of stakeholder engagement within an area of study and population that has been underrepresented in stakeholder-engaged research. The engagement practices within the SISTER Study can inform community-academic partnership practices in health equity research.

Aim:Social isolation in cancer patients is correlated with prognosis and is a potential mediator of treatment completion. Black women with endometrial cancer (EC) are at increased risk for social isolation when compared with White patients. We developed the Social Interventions for Support during Treatment for Endometrial Cancer and Recurrence (SISTER) study to compare and evaluate interventions to address social isolation among Black women with high-risk EC in USA. The primary objective of the SISTER study is to determine whether virtual support interventions improve treatment completion compared with Enhanced Usual Care. Secondary objectives include comparing effectiveness virtual evidence-based interventions and evaluating barriers and facilitators to social support delivery.Patients & methods:This is a multi-site prospective, open-label, community-engaged randomized controlled trial, consisting of three intervention arms: enhanced usual care, facilitated support group and one-to-one peer support. Primary outcome will be measured using relative dose. Qualitative semi-structured interviews will be conducted with a subset of participants to contextualize the relative degree or lack thereof of social isolation, over time.Data analysis:Primary analysis will be based on an intent-to-treat analysis. Multivariable analysis will be performed to determine the effect of the intervention on the primary and secondary outcomes of interest, relative dose and social isolation score. Semi-structured interviews will be qualitatively analyzed using inductive and deductive approaches of content analysis.Discussion/conclusion:Endometrial cancer mortality disproportionately affects Black women, and social isolation contributes to this disparity. The SISTER study aims to identify whether and to what extent differing social support vehicles improve key outcomes for Black women in the United States with high-risk EC.Clinical Trial Registration:NCT04930159 (ClinicalTrials.gov)

Objective: Hysterectomy is standard of care in the treatment of endometrial cancer. We will determine if endometrial cancer directed hysterectomy varies by race. Methods: The U.S. Surveillance, Epidemiology, and End Results (SEER) cancer registry was queried to identify 59,994 black and white women diagnosed with localized endometrial cancer from 2000-2009. Frequency of endometrial cancer directed hysterectomy was compared by race (white, black) and adjusted for age (<60 years, 60+) and tumor grade (low = grades I & II, high = grades III & IV). Reason for no hysterectomy was also queried. Five-year relative survival was also calculated using SEER*Stat 7.1.0. Results: Of the 59,994 women with localized endometrial malignancies in the study, 55,950 were white and 4,044 were black. White females with localized endometrial cancer were significantly more likely to undergo hysterectomy than their black counterparts (95.69% [94.88-96.5%] vs. 86.55% [86.55-92.4%]). Black women 60 and older were significantly less likely to receive hysterectomy than their white counterparts (87.50% vs. 94.96%). In accounting for grade, white women with low grade endometrial cancer were significantly more likely to undergo hysterectomy than black women (96.23% vs. 91.37%). There was no significant difference in hysterectomy in women less than age 60 or among those with high-grade disease. When reason for no hysterectomy was queried, it was found that reason “not recommended” was significantly higher for black women than white women (50.82% [44.28-58.05%] vs. 40.28% [37.79-42.90%]). Furthermore, when accounting for age and grade, black women were still more likely to have no surgery because it was not recommended, but the only statistically significant racial disparity was in women less than 60 years old (41.57% [38.26-44.97%] vs. 54.41% [46.02-62.56%]). Five-year survival for all women with hysterectomy was 98.8% (95% CI = 98.4-99.1%). White subjects that underwent hysterectomy had a significantly higher 5-year survival than black subjects (99.2% [98.7-99.5%] vs. 92.6% [90.6-94.1%]). The significant racial difference in 5-year survival persisted when accounting for age and grade. Conclusions: We found substantial racial disparities between black and white women with localized endometrial cancer in the frequency of hysterectomy performed and in 5-year survival. This, as yet, unexplained racial disparity merits further study to identify causative factors to ultimately improve health care outcomes for all women with endometrial cancer. Citation Format: Travis-Riley K. Korenaga, Kristy K. Ward, Michael T. McHale, Cheryl C. Saenz, Steven C. Plaxe. Racial disparities in surgical procedure and survival for endometrial cancer. [abstract]. In: Proceedings of the Fifth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2012 Oct 27-30; San Diego, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2012;21(10 Suppl):Abstract nr B59.

Facilitators and barriers to acceptability of a biopsy-first approach in the diagnostic evaluation for endometrial cancer among Black women.

Mortality associated with endometrial cancer is 98% higher among Black as compared with White women. A large body of literature has evaluated differential treatment patterns as a potential determinant of increased mortality among Black women. In most studies, receipt of individual endometrial cancer treatment components (i.e., surgery, radiation, chemotherapy) is compared between Black and White women. Moreover, individual treatment components are typically considered binary variables (received vs. not received) with the received category reflecting a wide spectrum of treatments received. For example, women who receive one vs. six cycles of chemotherapy would be similarly labeled as receiving chemotherapy, despite a clear difference in treatment intensity. In contrast, recent studies have begun to evaluate racial and ethnic differences in the complete course of treatment as a unit, within the context of established guidelines. The National Comprehensive Cancer Network guidelines provide evidence-based endometrial cancer treatment recommendations based on clinical trials and observational research. Surgery is the first step of guideline-concordant treatment and pathology factors captured from surgery inform adjuvant treatment recommendations. Since the distribution of tumor characteristics that guide treatment recommendations varies between Black and White women, we should expect racial differences in use of adjuvant radiation and chemotherapy. However, when conceptualizing treatment as guideline-concordant vs. discordant, racial and ethnic differences clearly signal disparate quality of care. In this presentation, we will discuss the need for research on endometrial cancer treatment disparities to shift from a paradigm of exploring individual treatment components to one in which receipt of guideline-concordant treatment is the focus. Moreover, through the lens of a recently funded grant, we will discuss the value of using an explicit disparities definition in analyses of guideline-concordant treatment, which allows for decomposition of the sources of racial and ethnic disparities. Differences in healthcare related to clinical need or preference are not considered sources of disparities, reflecting the normative view that these differences are acceptable, and therefore, just. On the other hand, unjust sources of disparities include the operation of healthcare systems, the legal and regulatory climate, and discrimination, among other factors. In addition to the selection of a rigorous and nuanced disparities definition, future research on guideline-concordant treatment disparities should investigate the role of multilevel factors that reflect the social determinants of health. Cancer health disparities are entrenched in the social determinants of health, which cannot be effectively addressed at the individual-level alone. Citation Format: Ashley S. Felix. Racial disparities in guideline-concordant endometrial cancer treatment [abstract]. In: Proceedings of the AACR Special Conference on Endometrial Cancer: Transforming Care through Science; 2023 Nov 16-18; Boston, Massachusetts. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(5_Suppl):Abstract nr IA008.

Racial disparities in young women with endometrial cancer

Adjuvant therapy following surgery is one of the most controversial areas in endometrial cancer, and consequently a number of clinical trials have been conducted over many years. It is obvious that adjuvant therapy will be withheld for the low-risk patient group, which has a favorable prognosis, and adjuvant therapy is considered to be delivered to intermediate- and high-risk patient populations.

Racial Disparities in Brachytherapy Treatment among Women with Cervical and Endometrial Cancers: A United States Cohort Study between 2004 and 2017

BackgroundSurgery is a cornerstone in management of ovarian and endometrial cancer. The European Society of Gynecological Oncology introduced quality indicators to improve management of these cancers. The optimal annual number of surgeries per unit was established for high-quality surgical treatment.Material/MethodsThe database of the National Health Fund on surgical management of endometrial and ovarian cancer was analyzed. Patients treated between 2017 and 2020 were included. Departments where patients underwent surgery were divided according to number of surgeries performed per year in endometrial cancer: ≥80, 79-50, 49-20, 19-0; and ovarian cancer: ≥100, 99-50, 49-20, 19-0. Optimal number of surgeries per center was defined as at least 100 and 80 surgeries per year in ovarian and endometrial cancer, respectively.ResultsTotally, there were 22 325 surgeries in 316 units and 10 381 surgeries in 251 units due to endometrial and ovarian cancer, respectively. Most surgeries in endometrial cancer (n=15 077; 67.5%) and ovarian cancer (n=9642; 92.88%) were performed in departments that did not meet optimal criteria in number of surgeries. Between 2017 and 2019, an increasing trend in number of surgeries per year in endometrial and ovarian cancer was found. In 2020, there was a decrease in the number of surgeries by 7.8% (n=453) and 8.6% (n=234) in endometrial and ovarian cancer, respectively.ConclusionsIn Poland, surgical treatment of ovarian and endometrial cancer is decentralized. Most cancer patients underwent surgery in low-volume general gynecologic departments. The COVID-19 pandemic impaired cancer management, leading to a decreased number of surgeries.

Endometrial cancer is the sixth most common cancer in women worldwide and most commonly occurs after the menopause (75%) (globocan.iarc.fr). About 319,000 new cases were diagnosed worldwide in 2012. Endometrial cancer is commonly considered as a potentially 'curable cancer,' as approximately 75% of cases are diagnosed before disease has spread outside the uterus (FIGO (International Federation of Gynecology and Obstetrics) stage I). The overall five-year survival for all stages is about 86%, and, if the cancer is confined to the uterus, the five-year survival rate may increase to 97%. The majority of women diagnosed with endometrial cancer have early-stage disease, leading to a good prognosis after hysterectomy and removal of the ovaries (oophorectomy), with or without radiotherapy. However, women may have early physiological and psychological postmenopausal changes, either pre-existing or as a result of oophorectomy, depending on age and menopausal status at the time of diagnosis. Lack of oestrogen can cause hot flushes, night sweats, genital tract atrophy and longer-term adverse effects, such as osteoporosis and cardiovascular disease. These changes may be temporarily managed by using oestrogens, in the form of hormone replacement therapy (HRT). However, there is a theoretical risk of promoting residual tumour cell growth and increasing cancer recurrence. Therefore, this is a potential survival disadvantage in a woman who has a potentially curable cancer. In premenopausal women with endometrial cancer, treatment induces early menopause and this may adversely affect overall survival. Additionally, most women with early-stage disease will be cured of their cancer, making longer-term quality of life (QoL) issues more pertinent. Following bilateral oophorectomy, premenopausal women may develop significant and debilitating menopausal symptoms, so there is a need for information about the risk and benefits of taking HRT, enabling women to make an informed decision, weighing the advantages and disadvantages of using HRT for their individual circumstances. To assess the risks and benefits of HRT (oestrogen alone or oestrogen with progestogen) for women previously treated for endometrial cancer. We searched the Cochrane Register of Controlled Trials (CENTRAL 2017, Issue 5), MEDLINE (1946 to April, week 4, 2017) and Embase (1980 to 2017, week 18). We also searched registers of clinical trials, abstracts of scientific meetings and reference lists of review articles. We included randomised controlled trials (RCTs), in all languages, that examined the efficacy of symptom relief and the safety of using HRT in women treated for endometrial cancer, where safety in this situation was considered as not increasing the risk of recurrence of endometrial cancer above that of women not taking HRT. Two review authors independently assessed whether potentially relevant studies met the inclusion criteria. We used standard methodological procedures expected by Cochrane. We identified 2190 unique records, evaluated the full text of seven studies and included one study with 1236 participants. This study reported tumour recurrence in 2.3% of women in the oestrogen arm versus 1.9% of women receiving placebo (risk ratio (RR) 1.17, 95% confidence interval (CI) 0.54 to 2.50; very low-certainty evidence). The study reported one woman in the HRT arm (0.16%) and three women in the placebo arm (0.49%) who developed breast cancer (new malignancy) during follow-up (RR 0.80, 95% CI 0.32 to 2.01; 1236 participants, 1 study; very low-certainty evidence). The study did not report on symptom relief, overall survival or progression-free survival for HRT versus placebo. However, they did report the percentage of women alive with no evidence of disease (94.3% in the HRT group and 95.6% in the placebo group) and the percentage of women alive irrespective of disease progression (95.8% in the HRT group and 96.9% in the placebo group) at the end of the 36 months' follow-up. The study did not report time to recurrence and it was underpowered due to closing early. The authors closed it as a result of the publication of the Women's Health Initiative (WHI) study, which, at that time, suggested that risks of exogenous hormone therapy outweighed benefits and had an impact on study recruitment. No assessment of efficacy was reported. Currently, there is insufficient high-quality evidence to inform women considering HRT after treatment for endometrial cancer. The available evidence (both the single RCT and non-randomised evidence) does not suggest significant harm, if HRT is used after surgical treatment for early-stage endometrial cancer. There is no information available regarding use of HRT in higher-stage endometrial cancer (FIGO stage II and above). The use of HRT after endometrial cancer treatment should be individualised, taking account of the woman's symptoms and preferences, and the uncertainty of evidence for and against HRT use.

Impact of quality of care on racial disparities in survival for endometrial cancer

The incidence of endometrial cancer is increasing, making it the fifth most common cancer worldwide. To date, however, there is no standard therapy for patients with recurrent endometrial cancer. Melatonin, a hormone secreted by the pineal gland, has been shown to have anti-tumor effects in various tumor types. Although melatonin is available as a supplement, it has not been approved for cancer treatment. Ramelteon, a selective melatonin receptor type 1 and 2 (MT1/MT2) receptor agonist, has been approved to treat sleep disorders, suggesting that ramelteon may be effective in the treatment of endometrial cancer. To determine whether this agent may be effective in the treatment of endometrial cancer, this study investigated the ability of ramelteon to suppress the proliferation and invasiveness of HHUA cells, an estrogen receptor-positive endometrial cancer cell line. Ramelteon at 10-8 M maximally suppressed the proliferation of HHUA cells, reducing the percentage of Ki-67 positive proliferating cells. This effect was completely blocked by luzindole, a MT1/MT2 receptor antagonist. Furthermore, ramelteon inhibited HHUA cell invasion and reduced the expression of the MMP-2 and MMP-9 genes. These results suggested that ramelteon may be a candidate for the treatment of recurrent endometrial cancer, with activity similar to that of melatonin.

Uterine cancer is the most common gynecologic malignancy in the United States, with an estimated 40,100 new cases and 7,470 deaths occurring in 2008. Although the incidence of endometrial cancer is lower among black women compared with white women, the proportion of cancer-related deaths among blacks is higher and has continued to rise over the past two decades. The authors conducted a survey of recent literature published in the English language and have used these articles as the basis for this review. The etiology for the racial disparity among black women with endometrial cancer is multifactorial and may be the result of barriers that impede access to care, an increased incidence of comorbidities among black women, inequalities in surgical care, adjuvant chemotherapy and radiation treatment, and underlying biological differences associated with more aggressive tumors that often develop in black women. Black women with endometrial cancer have a poorer prognosis compared with white women. Factors that contribute to this racial disparity include later diagnosis, treatment disparities, comorbid conditions, and genetic differences in tumors. An improved understanding of the causative factors associated with racial disparities in endometrial cancer outcome is needed to facilitate efforts aimed at correcting this important health care problem and providing individualized care to those at highest risk for poor outcome.

Endometrial cancer is the fourth most common cancer and the most common gynecological cancer diagnosed in the women in the United States. The lifetime risk of developing endometrial cancer is 2.58% in US women. The American Cancer Society estimates approximately 47,000 new cases and 8,120 deaths due to endometrial cancer in 2011 (Siegel et al. 2011). There does appear to be a significant difference in prognosis based on race. The incidence of endometrial cancer is higher in white women compared to the black women (age adjusted incidence rate: 24.8 vs. 20.9 per 100,000 women), but the death rate from endometrial cancer in the black women is almost two times that of the white women (age adjusted death rate: 3.9 vs. 7.2 per 100,000 women) (Howlader N). Furthermore, the incidence and the death rate have remained stable in the white women; although it has been rising steadily in the black women (by 1.7% per year and 0.8% per year, respectively) (Howlader N). The management strategies in endometrial cancer have evolved dramatically in the past two decades. Despite the advances in the treatment of endometrial cancer; the death rate from endometrial cancer remains high. Clearly, more effective treatment strategies are needed.

This review seeks to describe new fertility-sparing endometrial cancer (EC) treatment strategies that take into consideration the medical and general health background of patients. We particularly focus on the application of metformin, which is a biguanide widely prescribed for treatment of type 2 diabetes mellitus. Fertility-sparing treatment using progestin is considered a standard treatment option for patients with atypical endometrial hyperplasia (AEH) and EC who desire to conceive. A previous meta-analysis of fertility-sparing treatments revealed a high remission rate; however, high rates of relapse persisted. Most young patients with AEH and EC who are subjected to fertility-sparing treatment have a background of obesity, insulin resistance and abnormal glucose tolerance complicated with polycystic ovary syndrome. Recently, metformin has been attracting more attention in the field of cancer research. Several in vitro and in vivo reports regarding the efficacy of metformin in EC management have accumulated. Thus far, the efficacy of combining metformin with progestin has been revealed in a single phase II study of medroxyprogesterone acetate in combination with metformin as a fertility-sparing treatment for patients with AEH or EC. In addition to improving the metabolic profile of patients with EC having metabolic disorders, metformin supplementation may improve the long-term oncological outcome of these patients. To date, many clinical trials employing progestin and metformin as a fertility-sparing treatment of AEH and EC are ongoing. In the near future, it is expected that the clinical advantage of metformin progestin combination therapy will be clarified.