Unique Considerations in Early Detection,Risk,and Awareness of Endometrial Cancer in Black Women

Abstract

Endometrial cancer is the most common gynecologic cancer in the United States. Over the last several decades, the incidence of aggressive tumors, and thus the rate of death from disease, has increased significantly. The population most affected by these epidemiologic shifts are Black women. Symptom awareness, lack of treatment access, and failure of providers to provide guideline-concordant care are just some of the drivers behind these changes. Race as a social construct has historically categorized women into groups that are not reflective of the nuanced personalization that is required for cancer prevention strategies and targeted cancer treatments. There is, however, an increasing understanding that disaggregation by place of birth and social context are important to understand care-seeking behaviors, genetic drivers of disease, and factors that lead to deleterious outcomes. In this review, we will focus on specific individual-level influences that impact disease diagnosis and care-seeking among Black women, recognizing that the global disparities which exist in this disease encompass multiple domains. Such considerations are crucial to understanding drivers of self-efficacy and to develop programs for knowledge awareness and empowerment within a framework that is both useful and acceptable to these diverse communities at risk.

Introduction

Endometrial cancer (EC), which is cancer of the lining inside of the uterus, is the most common gynecologic malignancy in the United States. In 2023, there will be approximately 66,200 new cases of EC diagnosed in the United States. ¹ Over the last several years, the incidence of EC has increased such that the number of cases in women rivals colorectal cancer nationally. ¹ Of greater concern is the marked change in the mortality rate in women with EC. The age-standardized death rates for EC now outpace all other malignancies in women, ² emphasizing the public health urgency to address needs in diagnosis and treatment.

Currently, there are no screening tests for endometrial cancer, and patients are diagnosed when they develop symptoms such as postmenopausal bleeding (PMB).^3,4 Routine Pap testing does not detect EC. There are 2 main histologic categories of EC. Type I (low-grade) tumors, which are symptomatic early and often diagnosed when the disease is confined to the uterus, are typically associated with obesity, diabetes, and the overabundance of estrogen.^5-7 In contrast, Type II (high-grade) tumors are aggressive variants that metastasize early, are refractory to treatment, and associated with a poor prognosis. ⁵ New molecular subclassifications of EC have been established ⁸ and investigations into their clinical utility are ongoing.

Race is a social construct which has been shown to have a number of detrimental impacts manifested through delays in care, alterations in biology, and worse cancer outcomes. ⁹ In this review, Black race is used to characterize people of African descent, and White race as those of European descent. Here we provide a brief review of general racial disparities in endometrial cancer with an emphasis on awareness, early detection, and personalization in risk estimation specifically among Black women.

Racial Disparities in Endometrial Cancer

Black women are disproportionately affected by EC. Since 2002, EC has been more common among Black women than White women, ¹⁰ with a higher death rate (8.7/100,000 vs 4.4/100,000). ¹¹ Black women also have a higher risk for high-grade EC compared to White and Hispanic women on the order of 2–3-fold.^12-15 The hysterectomy (surgical removal of the uterus)-adjusted incidence rate for high-grade EC has increased steadily over the last 15 years for Black women, with poorer survival than Whites, even when matched by stage.^11,16,17 It is estimated that by 2040 this projected trend will not only continue, but that Black women will be even more disproportionally affected. ¹⁸ The most common symptom of EC is PMB.^3,4 Black women with PMB are less likely to undergo guideline-concordant diagnostic work-up, which further associates with higher stage and metastasis when a diagnosis is finally established. ¹⁹ Young Black women (<50 years) have higher EC mortality than White women of the same age. ²⁰

Further compounding the disparity in incidence of EC among Black women are overall worse treatment outcomes and disparate approaches to care. Relative to all other races, Black women receive less guideline-concordant treatment, ²¹ undergo fewer hysterectomies,^17,22 receive fewer minimally invasive procedures (which are considered standard of care),^23,24 and experience higher rates of recurrence than Whites. ²⁵ There is a 10-fold lower than expected rate of participation by Black women in Gynecologic Oncology Group (GOG) EC clinical trials compared with White women, with a progressively steady decline over the last several decades. ²⁶ Black women additionally experience lower socioeconomic status relative to White women as measured by income and education ²⁷ ; such socioeconomic deprivation is associated with worse survival EC outcomes. ²⁸ Taken in sum, the number of factors contributing to worse outcomes in Black women who are diagnosed with EC is significant. Thus, education for not only patients, but healthcare providers, including awareness of symptoms, early detection, minimization of treatment delays, and evidence-based treatment recommendations are crucial components in reducing the public health impact of this disease.

Endometrial Cancer Awareness

Despite being the most common gynecologic malignancy in the United States, there is poor general awareness of EC. Unfortunately, only several investigations have sought to assess knowledge and understanding of EC among general populations of women. Among these, the number of Black participants was only between 8 and 16% of the total study cohorts,^29,30 thus biasing results and precluding an understanding of perceptions for women at highest risk for aggressive disease. Nevertheless, the populations of women studied had poor knowledge about the roles of obesity, age, race (societal factors and genomic ancestry), and hormone use on EC risk.^29,30 In fact, Washington et al ³⁰ reported that only 4.8% of women believed race significantly increased the risk of EC. Higher educational level and greater income levels, however, were associated with better EC knowledge. ²⁹ Even when women with diagnoses of EC are queried, understanding of personal factors associated with risk is poor, ³¹ suggesting a significant need for improvements in education and awareness. Doll et al ³² performed a qualitative analysis of 15 Black women with EC to assess their experiences, describing both knowledge gaps in the understanding of menopause due to variation in community experience with hysterectomy, and misinterpretation of bleeding symptoms which should have prompted medical evaluation. As Black women in the United States have a higher incidence of hysterectomy for benign conditions,^33,34 the general lack of community knowledge about EC may be further compounded by limited interpersonal communication with their peers about the significance of PMB Figure 1.

Figure 1.

Female reproductive anatomy. Endometrial cancer arises from the endometrium, the inner lining of the uterine cavity.

Attitudes to Cancer and Barriers to Early Diagnosis Vary Among Black Women

Understanding symptom interpretation in the context of familial, community, work, and religious influences is important to modify care-seeking behavior. Women often normalize gynecologic cancer symptoms, attributing them to normal aging or current medication use. ³⁵ Cancer as a cause of symptoms is frequently dismissed. Persistent or severe symptoms, usually manifest as pain, are triggers to seek care.^32,35 Perceived barriers to pursuing medical care frequently include vague symptoms, competing time demands, and previous negative experiences with the healthcare system. ³⁵ Cook et al ³⁶ describe that women frequently assume pathologic changes are within the realm of normal, and that additional factors, including negative attitudes toward gynecologic care as passed down by relatives, and poor communication with practitioners, were deterrents to further medical evaluation.

Several race-agnostic studies have evaluated EC-specific knowledge about symptoms, treatment, disease course, and survival, and demonstrated that women, in addition to normalizing symptoms, do not seek medical attention because of negative attitudes toward gynecologic care and poor communication with practitioners.^35,36 General oncologic care-seeking among Black women is further complicated by medical mistrust, fatalistic cancer-related beliefs, and psychosocial concerns about relationships with family/community.^37-39 Mistrust of the medical community by Black patients has been well established and is as high as 33%. ⁴⁰ Such sentiment may significantly affect care-seeking behavior and has been reported to result in less genetic testing/counseling and worse medication compliance.^41,42 Mistrust among Black women has been associated with younger age and use of public insurance programs^40,43 and results in poorer compliance with screening, decreased likelihood of provider continuity, and less participation in clinical trials given concerns about “experimentation.”^39,40

Even within subpopulations of Black women of varying nativity, care-seeking behaviors may differ, underscoring the importance of evaluating Black women as a diverse group. Among Nigerian women with gynecologic cancers, the most common patient-related delays to seeking care included lack of knowledge, denial, and use of traditional treatments. ⁴⁴ In a cohort of Black African, Black Caribbean, and White British women with breast cancer in the United Kingdom, conservative attitudes and taboos about breast awareness and absence of pain were common among Black women and translated into care delays relative to White women. ⁴⁵ Poor symptom and risk factor knowledge, fear of cancer treatments, and embarrassment about disclosing symptoms to healthcare professionals were also common among Black patients. ⁴⁶ In a study of Black women with ovarian cancer done in the United States, erroneous beliefs about cancer etiology and self-reported religiosity were reported to be associated with treatment delays. ⁴⁷ Differences in cancer perception have also been demonstrated between Black Caribbean women and White women in the United Kingdom. ⁴⁸

Social determinants of access to care in the setting of cancer symptoms have been evaluated, but very few have included EC, and the scope has been limited. Data demonstrate that women with EC and low socioeconomic status, as determined by area of residency, have delays in care and present with advanced stage disease. ⁴⁹ In other cancers, issues with healthcare utilization ⁵⁰ and transportation, ⁵¹ as well as environments where fear of deportation is prevalent, ⁵² also influence care-seeking. Among patients with ovarian cancer, racial segregation has been shown to negatively impact survival in Black women. ⁵³ Increasing distance to medical doctors has also been associated with higher disease stage at presentation among Black women. ⁵⁴ While multiple studies have investigated the social epidemiologic determinations of EC access and outcomes among Black women as a group collectively,^55-59 there are limited data about these measures in subpopulations of women defined specifically by ancestry and nativity.

Associations Between Nativity, Ancestry, and Hereditary Genetics Among Subpopulations of Black Women With Endometrial Cancer

Several studies have sought to investigate EC disparities among diverse Black women, and specifically related to nativity and country of birth. In a 2017 report utilizing the Florida Cancer Data System (FCDS), a markedly increased odds of high-grade disease in Black women across all type II histologies was observed. ¹² Subsequent institutional-level evaluations at the University of Miami revealed Caribbean-born Black women present with higher stage III disease than US-born Black women (27.8% vs 2.5%, P < .01) and are more often uninsured (27.0% vs 14.4%, P = .03). ⁶⁰ There was also a suggestion that Caribbean-born Black women may have an overall survival benefit (HR .65 [95% CI .40–1.07]). ⁶⁰ Nativity was further evaluated in a larger study combining both Florida and New York State data by Pinheiro et al. ⁶¹ Caribbean-born women had a lower overall risk of developing a type II EC relative to US-born Black women, and across all histologies. Interestingly, when survival was evaluated, Caribbean nativity was not associated with improved outcomes. However, Hispanic ethnicity among Black women was associated with markedly improved overall survival. More granular analyses of EC among subpopulations of Caribbean-born Black women by specific country of birth have been performed using the FCDS. Relative to US-born Black women, women born in Jamaica and Haiti have significantly greater odds of high-grade EC (Haiti OR 3.08 [2.06–4.62] ⁶² ; Jamaica OR 2.32 [1.66–3.25]), ⁶² suggesting that specific country of birth is associated with risk. These results are contrary to those reported by Pinheiro et al and may suggest that disaggregation among Caribbean-born women is necessary to appreciate specific variations in risk by nativity. As there are more than 700 islands in the Caribbean region, evaluating women who are Caribbean-born as a monolith likely predisposes to bias in true risk estimates.

Recent data have demonstrated that African genomic ancestry is highly associated with specific EC histologies and molecular subclassifications. Sanchez-Covarrubias et al reported that increasing African ancestry is associated with both serous EC histology and copy number high (CNV) molecular classification, such that there is a linear relationship between percent African ancestry and risk. ⁶³ While further investigation into ancestry and molecular classification is needed, early data have shown that mitotic subtypes are more common in Black women, with worse progression-free survival. ⁶⁴ While the definitive etiology of these patterns remains to be fully characterized, consideration should be given to the role of the Hereditary Breast and Ovarian Cancer (HBOC) syndrome and specifically BRCA gene mutations. Population-based data have demonstrated that in the presence of a BRCA1 mutation, there is a higher ratio of observed:expected uterine serous carcinoma cases (O:E 22.2, CI 6.1–56.9, P < .001), suggesting a potential association of this disease with HBOC. ⁶⁵ This is especially important when considering that there is a high prevalence of HBOC throughout the Caribbean, which varies between countries. ⁶⁶ Further investigation into the germline predisposition of high-grade EC among Black women is needed.

Conclusion

The landscape of EC is changing. There are increasing rates of not just new disease, but death from disease, with Black women disproportionately affected. It has become abundantly clear that Black women cannot be seen as a uniform group. Country of birth, ancestry, and genetics all play a role in disease risk, prevalent subtypes, and outcomes. Care-seeking behaviors and perception of disease vary across geographies and backgrounds. In the setting of a disease that has no screening test, it is essential that there are continued investigations to understand disease etiology and characterize risk, considering both genetic and environmental influences. Developing educational programs designed to promote individual early care-seeking in the setting of symptoms while simultaneously crafting systems-level processes to achieve equitable care is crucial. A comprehensive yet personalized approach to EC in Black women is ultimately needed to reverse the concerning trend reports in new diagnoses, delays in care, and worse outcomes.