Major Disparities Research Articles

3.A. Round table: Towards a research agenda for burden of disease studies

Abstract What are the most relevant diseases in a country? Which risk factors are the strongest contributors to disease and death? How is the impact of different diseases evolving over time, and how does it compare between countries and within subnational units? As the need for prioritising the use of available resources constantly increases, a timely, sound and comprehensive answer to these fundamental questions is more than ever needed to inform public health decision-making. Driven by the impact of the Global Burden of Disease study, several researchers and national and international health institutes have adopted the burden of disease approach to address these questions. The complexity of the burden of disease approach however resulted in major disparities in research capacity across Europe. Furthermore, the current burden of disease landscape remains scattered, and researchers struggle to translate their findings to decision makers. The European Burden of Disease Network (COST Action CA18218) addresses these challenges by acting as a technical platform for integrating and strengthening capacity in burden of disease assessment across Europe and beyond. The different activities of the Network have helped to improve the quality and comparability of burden of disease estimates and increase their use in policy and practice. However, still many challenges remain. As a way of looking into the future applications of the burden of disease metrics, the European Burden of Disease Network took the initiative of developing a research agenda based on barriers and weaknesses identified within the activities of the network and input from researchers working regularly with burden of disease. As an initial step, a series of systematic literature review was carried to identify barriers and weaknesses in the computation of burden of disease estimates. These highlighted the differences in methodological choices that could hamper the comparability of results. This point was later identified as a key element of future development (abstract one). Secondly, the members of the network were consulted. Online questionnaires and structured consultations led to the identification of four main pillars of the future research agenda: transparency and availability, refining current methods, new applications, and prioritization of topics. In this workshop, we will present different activities within and outside the Network that correspond to the four pillars above described (abstract 2-4) and start the reflection on the future of burden of disease estimated. Key messages • Despite the wide use of the burden of disease approach, many challenges were identified in the replication of the methods and the need for further developments. • A new research agenda for burden of disease estimates will formalize a way to strengthen methodologies, interpretations and applications.

The ageing of people living with cystic fibrosis: what to expect now?

The prognosis of people with cystic fibrosis (pwCF) has improved dramatically with the introduction of cystic fibrosis transmembrane conductance regulator (CFTR) modulators (CFTRm). The ageing of the cystic fibrosis (CF) population is changing the disease landscape with the emergence of different needs and increasing comorbidities related to both age and long-term exposure to multiple treatments including CFTRm. Although the number of pwCF eligible for this treatment is expected to increase, major disparities in care and outcomes still exist in this population. Moreover, the long-term impact of the use of CFTRm is still partly unknown due to the current short follow-up and experience with their use, thus generating some uncertainties. The future spread and initiation of these drugs at an earlier stage of the disease is expected to reduce the systemic burden of systemic inflammation and its consequences on health. However, the prolonged life expectancy is accompanied by an increasing burden of age-related comorbidities, especially in the context of chronic disease. The clinical manifestations of the comorbidities directly or indirectly associated with CFTR dysfunction are changing, along with the disease dynamics and outcomes. Current protocols used to monitor slow disease progression will need continuous updates, including the composition of the multidisciplinary team for CF care, with a greater focus on the needs of the adult population.

Abstract A166: Towards Health Justice: Implementing Structural Competency in Women's Healthcare Education Towards Health Justice

Abstract Introduction: Significant health disparities persist in women's health, particularly among marginalized groups like racial/ethnic minorities, LGBTQ+ individuals, and those with disabilities. Addressing these inequities requires training healthcare providers in structural competency to recognizing how social, economic, political, and cultural structures influence health outcomes beyond just individual factors. Objectives: The purpose of this study is to conduct a comprehensive evaluation of the literature on structural competence in connection to health inequalities in women's health. The objectives include: (1) Reviewing the role of structural competence in addressing health disparities among in reproductive health ; (2) Analysing instructional methodologies related to structural competencies; and (3) Developing a strategic framework to address racial health disparities in women's health through structural competence. Methodology: A literature review was conducted using the Scopus, Google Scholar, and Web of Science databases. After applying specific inclusion and exclusion criteria, 463 publications were retained from 905 articles published between 2010 and 2023. Findings: Major health disparities experienced by women include lack of access to quality healthcare services, discrimination from providers, higher rates of chronic illnesses, mental health issues, and lack of autonomy in reproductive health decisions and influenced by cultural norms and expectations. Racial/ethnic minority women face additional disparities due to language/cultural barriers, provider biases, impact of social determinants, and discrimination.Structural competency approaches highlighted include using community health workers (CHWs), analyzing electronic health record (EHR) data to identify disparities, advocating for policy changes targeting social determinants, and integrating structural competency training in medical curricula.While no specific successful policy examples are provided, recommendations include expanding healthcare coverage, supporting community clinics, and addressing socioeconomic inequities through systemic interventions. Conclusion: Integrating structural competency into medical education holds transformative potential for alleviating persistent health disparities in women's health by equipping providers to recognize and confront the underlying structural factors perpetuating these inequities. Citation Format: Daina Charnelle Fougang, Dianne Wepa A/P Wepa, Charles Charnelle Mpofu. Towards Health Justice: Implementing Structural Competency in Women's Healthcare Education Towards Health Justice [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr A166.

Abstract C001: Global disparities in prostate cancer burden: An analysis of the GLOBOCAN 2020 database

Abstract Background: Prostate cancer (PCr) is one of the most common cancers among men globally, with considerable variations in incidence and death rates between racial/ethnic groups and geographical regions. With more than 1.4 million new cases reported in 2020, the global burden of PCr is predicted to double over the next two decades, to 2.9 million new cases and approximately 700,000 fatalities. Understanding the disparities in PCr is crucial for designing targeted treatments, and interventions and addressing health inequities. This study seeks to provide a comprehensive analysis of the recent global trends in PCr, focusing on incidence, mortality, and disparities in disease burden. Methods:This study analyzed age-standardized PCr incidence and mortality rates from the GLOBOCAN 2020 database for 174 countries, categorized by region and income level. Descriptive statistics and regression analyses were used to investigate the relationships between PCr rates and socioeconomic factors like the Human Development Index (HDI) and healthcare expenditure (HE). The study evaluated PCr distribution across age and geography, with statistical significance set at p < 0.05. Results:PCr incidence rates were highest in developed regions like Northern America (73.8/100,000), Western Europe (69.1/100,000), and Australia/New Zealand (88.2/100,000), and lowest in Eastern Asia (10.5/100,000) and Northern Africa (9.7/100,000). Mortality patterns were similar, with highest rates in the Caribbean (29.3/100,000) and Sub-Saharan Africa (26.6/100,000), and lowest in Eastern Asia (4.1/100,000) and Northern Africa (8.3/100,000). While incidence correlated positively with the HDI (p<0.001), mortality showed no significant association after adjusting for HE. Conclusion:This global analysis revealed major disparities in PCr incidence and mortality rates. Incidence was higher in developed regions, while mortality was elevated in economically disadvantaged areas. Further research is needed to understand the complex genetic, environmental, and socioeconomic factors driving these disparities. Key Takeaways: There is a continued need for targeted interventions to reduce the global burden of PCr and address disparities in disease burden. Citation Format: Olumide Arigbede, Sarah G. Buxbaum, Sara Falzarano, Suhn K. Rhie. Global disparities in prostate cancer burden: An analysis of the GLOBOCAN 2020 database [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr C001

United States Veterans' Utilization of Spinal Cord Injuries and Disorders Annual Evaluation Services

ObjectiveTo evaluate Veterans’ engagement in spinal cord injury and disorder (SCI/D) specialty annual evaluations (AEs). DesignCross-sectional retrospective cohort study. SettingSCI/D System of Care, United States Department of Veterans Affairs (VA). ParticipantsVeterans with SCI/Ds (N=14,662). InterventionsNot applicable. Main Outcome MeasuresReceiving SCI/D AEs during the study period (fiscal years [FY] 2019 and 2020). ResultsA total of 14,662 Veterans with SCI/Ds were included in the sample; 32.8% (n=4811) received 2 AEs, 28.8% (n=4219) received 1 AE, and 38.4% (n=5632) received no AEs, with an average of 0.9 AEs per Veteran over the 2-year study timeframe (range, 0-2y). Black Veterans had an 8% higher number of AEs than White Veterans after adjusting for other variables (adjusted relative risk [RR], 1.08; 95% confidence interval [CI], 1.04-1.12). Veterans who lived ≥240 minutes away from a VA SCI/D System of Care Center had 45% fewer AEs than Veterans who lived within 30 minutes (adjusted RR, 0.55; 95% CI, 0.52-0.59). Veterans with more SCI/D specialty visits had 90% more AEs than those with fewer visits (adjusted RR, 1.90; 95% CI, 1.78-2.03), whereas Veterans with more outpatient visits in VA primary care had 28% fewer AEs (adjusted RR, 0.72; 95% CI, 0.69-0.76). Veterans with higher comorbidity scores had 9% more AEs than Veterans with lower scores (adjusted RR, 0.66; 95% CI, 0.61-0.70). ConclusionsMore than half (62%) of Veterans received ≥1 SCI/D AE during FY19-20. Veterans living closer to a VA SCI/D System of Care Center/Hub had more engagement in SCI/D AEs. Veterans with SCI/Ds who used VA primary care outside of the SCI/D System of Care had fewer AEs. There were no major racial, age-based, or sex disparities in SCI/D AE usage. Our findings suggest the need for targeted intervention efforts to promote AE use among Veterans.

Legal Culture and Disability Rights in Indonesian Islamic Higher Education: A Review of Practices

This research aims to examine disability rights in relation to Islamic universities in Indonesia, paying attention to the legal culture concerning equal opportunities for disabled people. As a qualitative study with an empirical legal research method, this research will therefore gather information from various sources to examine current practices concerning regulations, facilities, and academic and social support, and disability education in Islamic higher learning institutions. The findings indicate that there is a major disparity between the legislation and the realities on the field. Implementation of strategies is poor, and a number of strategies are even ineffectual. Lack of physical infrastructure, academic accommodations, and training on the disability topics are some of the main challenges regarding full inclusion. Based on the study findings, it is suggested to enhance and expand the existing policies that include all parties and policies based on Islamic values that support equality and social justice. The final section reiterates the call for the reform of institutional culture and the advocacy of continuous public education to achieve cultural change.

Sex Differences in Alcohol Use: Is It All About Hormones?

Risky alcohol use and alcohol use disorders (AUD) are a rising problem in women, yet a major disparity in our understanding of what drives alcohol consumption in women remains. Historically biomedical research has focused on male subjects; however, recent increases in reporting of females, have highlighted major differences between the sexes. Here we review the current literature of the effect of gonadal steroid hormones (estrogens, androgens, and progestins), neurosteriods, and neurobiological factors on alcohol use in clinical and preclinical studies of both sexes. Further, we briefly discuss how fundamental sex differences in genetics, metabolism, neuroimmune, and stress responses may influence sex differences in alcohol intake. Comparing the sexes could aid in the discovery of novel therapeutics to treat AUD, and implementation of current treatment options in women.

Serum macroelements and microelements levels in periparturient dairy cows in relation to fatty liver diseases

BackgroundFatty liver in dairy cows is a common metabolic disease defined by triglyceride (TG) buildup in the hepatocyte. Clinical diagnosis of fatty liver is usually done by liver biopsy, causing considerable economic losses in the dairy industry owing to the lack of more effective diagnostic methods. Therefore, this study aimed to investigate the potential utility of blood biomarkers for the diagnosis and early warning of fatty liver in dairy cows.ResultsA total of twenty-four lactating cows within 28 days after parturition were randomly selected as experimental animals and divided into healthy cows (liver biopsy tested, n = 12) and cows with fatty liver (liver biopsy tested, n = 12). Inductively coupled plasma mass spectrometry (ICP-MS) was used to determine the macroelements and microelements in the serum of two groups of cows. Compared to healthy cows (C), concentrations of calcium (Ca), potassium (K), magnesium (Mg), strontium (Sr), selenium (Se), manganese (Mn), boron (B) and molybdenum (Mo) were lower and copper (Cu) was higher in fatty liver cows (F). Meanwhile, the observed differences in macroelements and microelements were related to delivery time, with the greatest major disparity between C and F occurring 7 days after delivery. Multivariable analysis was used to test the correlation between nine serum macroelements, microelements and fatty liver. Based on variable importance projection and receiver operating characteristic (ROC) curve analysis, minerals Ca, Se, K, B and Mo were screened as the best diagnostic indicators of fatty liver in postpartum cows.ConclusionsOur data suggested that serum levels of Ca, K, Mg, Se, B, Mo, Mn, and Sr were lower in F than in C. The most suitable period for an early-warning identification of fatty liver in cows was 7 days after delivery, and Ca, Se, K, B and Mo were the best diagnostic indicators of fatty liver in postpartum cows.

Standards for levels of lead in soil and dust around the world

Abstract Lead poisoning is a serious environmental health problem in every country in the world. Exposure to lead results in neurocognitive and behavioral changes, has adverse effects on the immune system, causes anemia, hypertension and perturbs other organ systems. The effects of lead poisoning are most critical for children because their bodies are growing and developing, and particularly because agents that reduce cognitive function and attention span as well as promote disruptive behavior will have life-long consequences. Lead exposure, especially to children, is a major health disparity issue. If the next generation starts with reduced cognitive ability, there will be significant barriers for development of skills and country-wide development. While there are many sources of exposure to lead, the commonest source is lead in soil and dust. Since lead is an element, it does not go away and past releases of lead into the environment remain as soil and dust contamination. This is an especially important route of exposure to children because children regularly play in soil and are exposed via hand-to-mouth activity. In addition to indoor sources of lead, contaminated soil is tracked on shoes or feet and blown by air currents into homes, accumulating in household dust which is a major source of exposure for both children and adults. The purpose of this review is to determine standards presumed to be health protective for lead and dust in different countries. We find that many countries have no standards for lead in soil and dust and rely on standards set by the World Health Organization or the US Environmental Protection Agency, and these standards may or may not be enforced. There is considerable variation in standards set by other countries.

Latin America and cancer clinical trials: Underrepresented region with significant growth potential.

e23038 Background: Latin America (LATAM) represents 8.4% of the world's population and has a growing cancer incidence compared with other regions. However, most clinical trials are conducted in high-income countries. The clinical research regulatory regimen in LATAM has been evolving consistently in the last decade and now is stable and mature, and data quality is comparable to other geographies. Enhanced LATAM involvement in global clinical trials would help these studies to meet recruitment goals, increase diversity, and reduce costs and perhaps timelines associated with clinical research. This abstract shows the current landscape of clinical research in LATAM trough data and experience of a global clinic research organization (CRO) (Fortrea). Methods: We obtained the 2020 cancer incidence in Brazil, Mexico, Argentina, Chile, Peru, Colombia, LATAM, and worldwide, from the World Health Organization’s GLOBOCAN database, as well as the information about ongoing, terminated, or completed clinical trials in these regions using Citeline’s database, from 2018 to 2023. We gathered LATAM countries' regulatory approval timelines from Fortrea’s database. Results: Overall, 7.7% of all cancer cases in 2020 were diagnosed in LATAM; however, only 3.64% of oncology trials were conducted there. The major disparities are in prostate cancer (15.2% vs 3.9% of cases and trials, respectively), followed by thyroid (10.8% vs 3.7%), cervix uteri (9.8% vs 4.6%), leukemia (8.1% vs 3.6%), and colorectal (7% vs 2.51%). Brazil had 3.1% of all cases but 1.9% of trials, while Mexico had 1% vs 1.3%, Argentina had 0.7% and 1.3%, Chile had 0.3% vs 0.7%, Peru had 0.4% vs 0.6%, and Colombia had 0.6% and 0.45% respectively. Regarding trial phases, 0.7% of Phase I trials were run in LATAM, 2.2% of Phase II, 15.6% of Phase III, and 2.8% of Phase IV. In the Table below, we present the proportion of clinical trials in LATAM in the past 5 years, based on the actual enrollment first date. Regulatory approval timelines in LATAM vary among countries, being 4.5 months in Argentina, 4 to 7 months in Brazil, 4.6 months in Chile, 7 months in Colombia, 2.8 months in Mexico, and 9 months in Peru. Conclusions: As a region, LATAM has been underrepresented in the clinical research scenario in the past five years, including in much-needed areas like prostate, colorectal, and cervical cancer. It is better represented in phase III studies but has almost negligible participation in other trial phases. There are differences among individual countries, with Brazil being underrepresented as opposed to Argentina and Mexico. Start-up timelines are variable among countries but overall comparable to other regions. We notice a significant potential to increase the number of clinical trials in LATAM. [Table: see text]

A Scoping Review of Trends in the Size of Lesbian, Gay, and Bisexual Tobacco Use Disparities, 1996-2020, United States and Canada.

Purpose: Tobacco use is a major health disparity for lesbian, gay, bisexual, and transgender (LGBT) populations compared with heterosexual/cisgender populations. In this scoping review, we aimed to determine if LGBT tobacco use disparities are improving or worsening over time and if trends in disparities differed across subgroups. Methods: We included articles that longitudinally explored youth and adult LGB tobacco use in the United States and Canada after searching four databases and capturing records through July 2022. Two reviewers independently screened the title/abstract and full text of 2326 and 45 articles, respectively. Eleven articles from 18 larger assessments met inclusion criteria, spanning data collection from 1996 to 2020. Results: All studies consistently demonstrated tobacco disparities for LGB populations. No articles examined longitudinal transgender tobacco disparities. Most studies focused on smoking combustible cigarettes. Disparities in heavy or daily use for all LGB youth subgroups compared with heterosexual samples appear to be shrinking longitudinally. Results for early-onset, current, and lifetime smoking were less consistent. Adult evidence was relatively sparse; however, after 2010, studies show diminishing disparities over time, except for current smoking by bisexual women. Conclusions: Large tobacco use disparities persist for LGB populations, although the size of disparities may be decreasing for some groups. Initiatives for lesbian and bisexual women and girls should be prioritized, in addition to interventions addressing LGB smoking broadly. Surveillance instruments should uniformly and consistently assess LGBT identities and tobacco use behaviors.

Challenges in Evaluating a Community-Level Intervention to Address Root Causes of Youth Violence

Violence disproportionately impacts Black American youth, representing a major health disparity. Addressing the possible root causes of structural inequities to reduce violence may increase the impact of prevention strategies. However, efforts to evaluate the impact of such interventions pose numerous methodological challenges, particularly around selecting an effective evaluation design to detect change at the community level, with adequate power and sampling, and appropriate constructs and measurement strategies. We propose a multiple baseline experimental design to evaluate the impact of a community-level youth violence and suicidality prevention strategy. A multiple baseline experimental design with multiple community units balances the need for scientific rigor with practical and values-based considerations. It includes randomization and plausible counterfactuals without requiring large samples or placing some communities in the position of not receiving the intervention. Considerations related to the conceptualization of the logic model, mechanisms of change, and health disparity outcomes informed the development of the measurement strategy. The strengths and weaknesses of a multiple baseline experimental design are discussed in comparison to versions of randomized clinical trials. Future health disparity intervention evaluation research will benefit from (1) building a shared sense of urgent public need to promote health; (2) respecting the validity of values- and partnership-based decision-making; and (3) promoting community-based and systems-level partnerships in scientific grant funding. The described study has been registered prospectively at clinicaltrials.gov, Protocol Record 21–454.

Principals’ Demographic Qualities and the Misuse of School Material Capital in Secondary Schools

Abstract Previous studies tend to not only assess principals’ demographic variables but also use other dependent variables, such as administrative effectiveness, job performance, and student achievement. In the literature, principals’ demographic qualities and the misuse of material capital have been under-assessed. This study used a quantitative approach to investigate the demographic attributes of principals and the abuse of school material capital in secondary schools. Using a questionnaire, data were gathered from 667 secondary school administrators in Cross River State, Nigeria. The findings revealed significant differences in the misuse of school material capital by principals of different ages, professional qualifications, and years of experience. However, major disparities between male and female principals were not identified. More specifically, principals who were older, seasoned, and possessed bachelor’s and Master of Education degrees were efficient managers of school material capital. A high rate of misuse was found among principals who were younger and inexperienced than their counterparts who were young, less experienced, and possessed a postgraduate diploma in education, as well as other professional academic qualifications unrelated to the field of education (e.g., HND, BSc, BA, and MSc). Based on these findings, key implications for quality service delivery and administrative effectiveness were discussed.

Major MH disparities found among trans vs. cis youth

Despite broad improvements in attitudes toward gender minorities, a new study examining mental health disparities in transgender individuals compared to the cisgender population has found alarming increases over several years, prompting researchers to call for new policies to address the worsening mental health of transgender and gender nonconforming people in the United States.

A Clinical Study of Intraoperative Perfusion Chemotherapy in Gastric Cancer: A Prospective Cohort Study.

Gastric cancer (GC) is the third largest cause of cancer-related death worldwide, with major geographic disparities in incidence and outcomes. Sociodemographic indicators, food habits, and genetic predispositions all add to the load. Despite advances in systemic treatments, peritoneal metastasis remains a concern, with intraperitoneal chemotherapy (IPC) emerging as a promising treatment option. A prospective cohort research was done, with 30 GC patients receiving cytoreductive surgery (CRS) followed by lobaplatin-based intraoperative chemotherapy. The study evaluated postoperative complications, survival rates, and disease recurrence using Statistical Package for the Social Sciences (SPSS) version 25.0(IBM SPSS Statistics, Armonk, NY) for data analysis. The purpose of this study is to assess the effectiveness, safety, and dependability of lobaplatin as an intraoperative chemotherapeutic agent in patients having gastric cancer surgery, with a particular emphasis on those patients who do not have distant metastases. The study population had a balanced gender distribution, with an average age of 44.83 years. Most patients had advanced-stage cancer (T3 and T4), and lobaplatin treatment resulted in a low frequency of serious postoperative sequelae. Preliminary studies suggest that lobaplatin is a safe and potentially effective IPC drug for GC, with few side effects and adequate survival rates. Lobaplatin shows promise as an intraoperative chemotherapeutic treatment for gastric cancer, necessitating more research in bigger, randomized controlled studiesto determine its efficacy and safety profile. The study emphasizes the need for novel treatment strategies to enhance the prognosis of GC patients, particularly those with peritoneal involvement.

Lifecycle of surgical devices: Global, environmental, and regulatory considerations.

Technological advancements, improved surgical access, and heightened demand for surgery have fueled unprecedented device and supply turnover impelling wealthy hospitals to upgrade continually and sell, donate, recycle, or dispose of used, expired, antiquated, or surplus goods. This paper reviews the issues related to device and supply lifecycles and discusses the opportunities and challenges they present for sustainable surgical growth in low- and middle-income (LMICs) countries. This review found, in LMICs countries, regulatory disparities persist that limit effective harmonization secondary to highly variable national policies and a lack of prioritized enforcement. Heterogeneity in the regulatory landscape, specifically in the classification, nomenclature, and identification of medical devices, encumbers effective regulation and distribution. Once devices are sold, donated, or reused in LMICs countries, complexities arise in regulatory compliance, maintenance, and appropriate use of these technologies. At the end of the lifecycle, waste management poses significant obstacles with limited resources hindering the implementation of best practices. There are major disparities in access to quality surgical equipment and supplies around the world. Improved communication between relevant stakeholders and harmonization of manufacture and disposal regulations will be needed to ensure adequate and appropriate responses to these challenges. Not applicable.

Abstract 2137: Racial disparities in triple-negative breast cancer (TNBC) mortality rates in Hampton Roads Virginia and the effects of SIAH expression on prognosis

Abstract Background: While high-resolution imaging and advancements in therapies have significantly improved breast cancer survival rates, 43,170 breast cancer patients will die in the United States in 2023 alone. Triple-negative breast cancer (TNBC) is the most aggressive breast cancer subtype and disproportionately affects BRCA1 mutation carriers and young black women. Black/African American (AA) patients have the highest mortality and the shortest survival of any racial/ethnic group in the US. Persistent cancer racial disparities remain due to a variety of risk factors. The SEER/CDC data show an 8% lower breast cancer incidence rate and a 41% higher mortality rate in Black/AA patients compared to their white counterparts. Methods: Chart review was conducted using Sentara MD Office/EPIC and VOA iKnowMedicine portals to update tumor relapse, metastasis, and survival in 577 TNBC patients. Supported by strong evidence in developmental, evolutionary, and cancer biology, we hypothesize that persistent EGFR/K-RAS/SIAH pathway activation is a major driving force of TNBC malignancy, racial disparity, early relapse, and high mortality. We propose to integrate SIAH expression to augment the existing clinicopathological parameters to improve patient risk stratification, therapy quantification, and relapse/survival prediction at the 1st-line neoadjuvant settings. Results: We report that cancer disparity and high mortality rates are even more pronounced in our racially-diverse communities in Hampton Roads Virginia. We discovered that SIAH is a tumor-specific, therapy-responsive, and prognostic biomarker in TNBC. High SIAH expression in residual tumors reflects tumor-driving EGFR/K-RAS/SIAH pathway activation (ON) that will predict cancer disparity, treatment resistance, early relapse, and poor survival. Low SIAH expression in residual tumors reflect EGFR/K-RAS/SIAH pathway inactivation (OFF) that will predict tumor remission and prolonged survival. Conclusion: We detect a major racial disparity of TNBC patients at Sentara-EVMS-VOA. Our local Black/AA TNBC patients have a 1.6-fold higher mortality rate than their White counterparts. Encouraged by our preliminary data, we aim to develop a SIAH-centered biomarker panel by measuring the EGFR/K-RAS/SIAH pathway activation (ON)/inactivation (OFF), and use SIAH as a new prognostic biomarker to risk stratify patients, detect cancer racial disparities, forecast tumor relapse, and predict patient survival at 1st-line neoadjuvant settings. By targeting SIAH, individualized treatments can be created to allow for increased survival rates in at risk individuals with more aggressive TNBCs. Citation Format: Claire B. Piatak, Taylor N. Drake, Ashleigh Hannah, Jonathan Baker, Caroline L. Dasom, Emily L. Breeding, Janet S. Winston, Billur Samli, Rick Jansen, Michael Danso, Richard A. Hoefer, Amy H. Tang. Racial disparities in triple-negative breast cancer (TNBC) mortality rates in Hampton Roads Virginia and the effects of SIAH expression on prognosis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2137.

Abstract 7664: Early detection of racial disparity and treatment resistance in triple negative breast cancer

Abstract Introduction: Triple-negative breast cancer (TNBC) is an aggressive breast cancer subtype that disproportionately affects BRCA1 mutation carriers and young Black/African American (AA) women. Black/AA patients have the highest mortality and the shortest survival of any racial/ethnic group in the US. With the approval of pembrolizumab, the addition of immune checkpoint blockade (ICB) to neoadjuvant chemotherapy (NACT) has become the standard of care (SOC) for high-risk early-stage TNBC. The pathologic complete response (pCR) is a reliable prognostic marker that correlates with tumor remission and good outcome, whereas pathologic incomplete response (pIR) with high residual cancer burden (RCB) is often associated with early relapse, treatment resistance, and poor survival. Many similarly-treated patients with identical TNM and RCB classifications still experience racial disparity, different relapse rates, and disparate survival. Current methods fall short in predicting tumor recurrence/chemo-resistance/patient survival with high accuracy in the clinic. Methods: We detected a major racial disparity in our large regional cohorts of TNBC patients (> 1,000 patients), of which 48% patients are Black/AA and 48% patients are white patients, at the Sentara Cancer Network and VCU Massey Comprehensive Cancer Center, that have historically provided excellent healthcare and quality cancer care to the social-economically-disadvantaged, medically underserved, and underinsured racial/ethnic minorities in low income communities in Virginia. Despite Sentara/VCU’s best efforts, Black/AA breast cancer patients still suffer 70-100% higher MBC mortality, and the worst survival compared to their white counterparts, based on our clinical studies and the SEER/CDC databases. Result: We showed that persistent EGFR/RAS/SIAH pathway activation is a major driving force of TNBC malignancy. The most downstream and evolutionarily conserved signaling gatekeeper, SIAH, is an RING domain E3 ligase that is a high-resolution prognostic biomarker for patient risk stratification and racial disparity prediction in TNBC. High SIAH expression in residual tumors reflects ineffective NACT/IO therapy and persistent EGFR/K-RAS/SIAH pathway activation (ON) that drives tumor relapse, resistance, and reduced survival. Low SIAH expression in residual tumors reflects effective NACT/IO therapy and EGFR/K-RAS/SIAH pathway inactivation (OFF) that predicts tumor remission, good outcome, and prolonged survival. We found that SIAH expression is 2.0-fold higher in Black/AA patients’ residual tumors than in the white patients’ residual tumors, mirroring a 1.8-2.0-fold higher death rates in the Black/AA patients than the white patients. Conclusion: In this study, we demonstrate the prognostic power of SIAH for patient risk stratification, therapy quantification, and relationship to cancer racial disparity in TNBC. Citation Format: Amy H. Tang, Richard A. Hoefer, Mary L. Guye, Billur Samli, Janet S. Winston, Jennifer Koblinski, Valentina Robila, Michael O. Idowu, Rick J. Jansen, Harry D. Bear. Early detection of racial disparity and treatment resistance in triple negative breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 7664.

Abstract PR007: Patient derived organoids as a model to study estrogen mediated endometrial cancer

Abstract The purpose of our study was to develop a more optimal in vitro model to study the mechanisms of hormone action on endometrial cancer. Endometrial cancer (EC) represents a major health disparity with a 21% increase in mortality in African American women. The cause for this excess mortality is unknown. Endometrial cancer is commonly characterized by histological subtype into Endometrioid or Non-Endometrioid with estrogen being a driver for many endometroid type tumors. Most EC cell lines do not have high expression of estrogen receptor or do not respond to physiological levels of hormones in vitro; this lack of functional experimental models has hampered progress in the study of this disease. We have developed Patient Derived Organoids (PDOs) from 9 patient-derived xenografts (PDX) that are from both African American and Non-Hispanic Caucasian women with various stages and subtypes of EC, as a model to study EC. This model system captures the characteristics of different histological and molecular subtypes in vitro, as they maintain not only EC tumor cells but also cells from the adjacent tumor stroma. Our developed PDOs were derived from multiple molecular subtypes of EC that have different characteristics and genomic features, allowing us to observe differences in the basal properties of each tumor in vitro. The use of this organoid model system is advantageous for studying EC because growth characteristics are similar to an in vivo model, with the organoids preserving the genotype and phenotype of the native EC, allowing us to observe cellular interactions. We have observed inter-organoid variation of protein expression of β-catenin, E-cadherin, and vimentin, proteins playing a pivotal role in cellular contact, signaling, and epithelial-mesenchymal transition (EMT). Using qPCR and Western blot analysis we have observed high expression levels of estrogen receptor and progesterone receptor in endometrioid type PDOs to begin the exploration of hormonal signaling in this model. Treatment of these same PDOs with β-estradiol resulted in an increase in proliferation of the stromal cells. Single cell RNA sequencing was performed on two PDO’s that had the highest expression of progesterone and estrogen receptors. This analysis demonstrated cell population heterogeneity with multiple cell clusters forming with differential gene expression. From this analysis we can see that the cells recapitulate the gene expression from the tumor of origin, with cells containing the same genetic mutation as the original patient. These results make this model potentially good for studying hormone signaling cascades seen in EC patients that have not been previously observed in established EC cell lines. These studies will also aid in the opportunity to explore the function of differential cell types in the pathogenesis of this disease. Citation Format: Breanna M.W. Jeffcoat, Andrew B. Galdden, Russell R. Broaddus. Patient derived organoids as a model to study estrogen mediated endometrial cancer [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 PR007.

Regional excess mortality in France during COVID-19 pandemic: the first three epidemic periods (March 2020-June 2021).

This study aimed to describe the mortality excess during the three first epidemic periods of COVID-19 in all regions of France. Two complementary approaches were implemented. First, we described the number of death of patients infected with or diagnosed with COVID-19 in health care (HC) and medico-social (MS) institutions. Then, we estimated general all-cause mortality excess (all ages) by comparing the mortality observed with the expected mortality. We used a daily number of death model according to a negative binomial distribution, as a function of the long-term trend in mortality (penalized spline function of time) and its seasonal variation (cyclic spline function). The model provided expected mortality during epidemic periods with a 95% credibility interval. Each region defined three epidemic periods, including the overseas territories. The two approaches were consistent in the most affected regions but there are major regional disparities that vary according to the epidemic period. There is an east-west gradient in the relative excess of deaths from all-causes during each epidemic period. The deaths observed in HC and MS institutions alone do not explain the excess (or deficit) of mortality in each region and epidemic period. An analysis by age group according to the two approaches and a comparison of death specific causes could provide a better understanding of these differences. Electronic death registration system (mortality by medical causes) would allow a rapid mortality related estimation to an emerging pathology like Coronavirus Disease-2019 (COVID-19) but is still insufficient for real-time medical causes of death monitoring.