Disparities in Access to Liver Transplant Referral and Evaluation among Patients with Hepatocellular Carcinoma in Georgia.

Liver transplantation offers the best survival for patients with early-stage hepatocellular carcinoma (HCC). Prior studies have demonstrated disparities in transplant access; none have examined the early steps of the transplant process. We identified determinants of access to transplant referral and evaluation among patients with HCC with a single tumor either within Milan or meeting downstaging criteria in Georgia.Population-based cancer registry data from 2010 to 2019 were linked to liver transplant centers in Georgia. Primary cohort: adult patients with HCC with a single tumor ≤8 cm in diameter, no extrahepatic involvement, and no vascular involvement. Secondary cohort: primary cohort plus patients with multiple tumors confined to one lobe. We estimated time to transplant referral, evaluation initiation, and evaluation completion, accounting for the competing risk of death. In sensitivity analyses, we also accounted for non-transplant cancer treatment.Among 1,379 patients with early-stage HCC in Georgia, 26% were referred to liver transplant. Private insurance and younger age were associated with increased likelihood of referral, while requiring downstaging was associated with lower likelihood of referral. Patients living in census tracts with ≥20% of residents in poverty were less likely to initiate evaluation among those referred [cause-specific hazard ratio (csHR): 0.62, 95% confidence interval (CI): 0.42-0.94]. Medicaid patients were less likely to complete the evaluation once initiated (csHR: 0.53, 95% CI: 0.32-0.89).Different sociodemographic factors were associated with each stage of the transplant process among patients with early-stage HCC in Georgia, emphasizing unique barriers to access and the need for targeted interventions at each step. SIGNIFICANCE: Among patients with early-stage HCC in Georgia, age and insurance type were associated with referral to liver transplant, race, and poverty with evaluation initiation, and insurance type with evaluation completion. Opportunities to improve transplant access include informing referring providers about insurance requirements, addressing barriers to evaluation initiation, and streamlining the evaluation process.

Considerations in Narrowing the Breast Cancer Mortality Gap Between Black and White Women.

This Viewpoint discusses 3 key measures of population-based surveillance along with areas for future investigation to reduce racial disparities in breast cancer mortality.

Redlining-associated methylation in breast tumors: the impact of contemporary structural racism on the tumor epigenome.

Purpose: Place-based measures of structural racism have been associated with breast cancer mortality, which may be driven, in part, by epigenetic perturbations. We examined the association between contemporary redlining, a measure of structural racism at the neighborhood level, and DNA methylation in breast tumor tissue. Methods: We identified 80 Black and White women diagnosed and treated for a first-primary breast cancer at Emory University Hospitals (2008-2017). Contemporary redlining was derived for census tracts using the Home Mortgage Disclosure Act database. Linear regression models were used to calculate the association between contemporary redlining and methylation in breast tumor tissue. We also examined epigenetic age acceleration for two different metrics, regressing ß values for each cytosine-phosphate-guanine dinucleotide (CpG) site on redlining while adjusting for covariates. We employed multivariable Cox-proportional hazards models and 95% confidence intervals (CI) to estimate the association between aberrant methylation and mortality. Results: Contemporary redlining was associated with 5 CpG sites after adjustment for multiple comparisons (FDR<0.10). All genes were implicated in breast carcinogenesis, including genes related to inflammation, immune function and stress response (ANGPT1, PRG4 and PRG4). Further exploration of the top 25 CpG sites, identified interaction of 2 sites (MRPS28 and cg11092048) by ER status and 1 site (GDP1) was associated with all-cause mortality. Contemporary redlining was associated with epigenetic age acceleration by the Hannum metric (ß=5.35; CI 95%=0.30,10.4) and showed positive but non-significant correlation with the other clock. Conclusion: We identified novel associations between neighborhood contemporary redlining and the breast tumor DNA methylome, suggesting that racist policies leading to inequitable social and environmental exposures, may impact the breast tumor epigenome. Additional research on the potential implications for prognosis is needed.

Drivers of racial, regional, and socioeconomic disparities in late-stage breast cancer mortality.

BACKGROUND: The authors identified tumor, treatment, and patient characteristics that may contribute to differences in breast cancer (BC) mortality by race, rurality, and area-level socioeconomic status (SES) among women diagnosed with stage IIIB-IV BC in Georgia. METHODS: Using the Georgia Cancer Registry, 3084 patients with stage IIIB-IV primary BC (2013-2017) were identified. Cox proportional hazards regression was used to calculate the hazard ratios (HRs) and 95% confidence intervals (CIs) comparing mortality among non-Hispanic Black (NHB) versus non-Hispanic White (NHW), residents of rural versus urban neighborhoods, and residents of low- versus high-SES neighborhoods by tumor, treatment, and patient characteristics. The mediating effects of specific characteristics on the association between race and BC mortality were estimated. RESULTS: Among the study population, 41% were NHB, 21% resided in rural counties, and 72% resided in low SES neighborhoods. The authors observed mortality disparities by race (HR, 1.27; 95% CI, 1.13, 1.41) and rurality (HR, 1.14; 95% CI, 1.00, 1.30), but not by SES (HR, 1.04; 95% CI, 0.91, 1.19). In the stratified analyses, racial disparities were the most pronounced among women with HER2 overexpressing tumors (HR, 2.30; 95% CI, 1.53, 3.45). Residing in a rural county was associated with increased mortality among uninsured women (HR, 2.25; 95% CI, 1.31, 3.86), and the most pronounced SES disparities were among younger women (<40 years: HR, 1.46; 95% CI, 0.88, 2.42). CONCLUSIONS: There is considerable variation in racial, regional, and socioeconomic disparities in late-stage BC mortality by tumor, treatment, and patient characteristics.

Understanding gastrointestinal cancer mortality disparities in a racially and geographically diverse population.

BACKGROUND: Gastrointestinal (GI) cancers represent a diverse group of diseases. We assessed differences in geographic and racial disparities in cancer-specific mortality across subtypes, overall and by patient characteristics, in a geographically and racially diverse US population. METHODS: Clinical, sociodemographic, and treatment characteristics for patients diagnosed during 2009-2014 with colorectal cancer (CRC), pancreatic cancer, hepatocellular carcinoma (HCC), or gastric cancer in Georgia were obtained from the Surveillance, Epidemiology, and End Results Program database. Patients were classified by geography (rural or urban county) and race and followed for cancer-specific death. Multivariable Cox proportional hazards models were used to calculate stratified hazard ratios (HR) and 95% confidence intervals (CIs) for associations between geography or race and cancer-specific mortality. RESULTS: Overall, 77% of the study population resided in urban counties and 33% were non-Hispanic Black (NHB). For all subtypes, NHB patients were more likely to reside in urban counties than non-Hispanic White patients. Residing in a rural county was associated with an overall increased hazard of cancer-specific mortality for HCC (HR = 1.15, 95% CI = 1.02-1.31), pancreatic (HR = 1.11, 95% CI = 1.03-1.19), and gastric cancer (HR = 1.17, 95% CI = 1.03-1.32) but near-null for CRC. Overall racial disparities were observed for CRC (HR = 1.18, 95% CI = 1.11-1.25) and HCC (HR = 1.12, 95% CI = 1.01-1.24). Geographic disparities were most pronounced among HCC patients receiving surgery. Racial disparities were pronounced among CRC patients receiving any treatment. CONCLUSION: Geographic disparities were observed for the rarer GI cancer subtypes, and racial disparities were pronounced for CRC. Treatment factors appear to largely drive both disparities.

Neighborhood-Level Redlining and Lending Bias Are Associated with Breast Cancer Mortality in a Large and Diverse Metropolitan Area.

BACKGROUND: Structural inequities have important implications for the health of marginalized groups. Neighborhood-level redlining and lending bias represent state-sponsored systems of segregation, potential drivers of adverse health outcomes. We sought to estimate the effect of redlining and lending bias on breast cancer mortality and explore differences by race. METHODS: Using Georgia Cancer Registry data, we included 4,943 non-Hispanic White (NHW) and 3,580 non-Hispanic Black (NHB) women with a first primary invasive breast cancer diagnosis in metro-Atlanta (2010-2014). Redlining and lending bias were derived for census tracts using the Home Mortgage Disclosure Act database. We calculated hazard ratios and 95% confidence intervals (CI) for the associations of redlining, lending bias on breast cancer mortality and estimated race-stratified associations. RESULTS: Overall, 20% of NHW and 80% of NHB women lived in redlined census tracts, and 60% of NHW and 26% of NHB women lived in census tracts with pronounced lending bias. Living in redlined census tracts was associated with a nearly 1.60-fold increase in breast cancer mortality (hazard ratio = 1.58; 95% CI, 1.37-1.82) while residing in areas with substantial lending bias reduced the hazard of breast cancer mortality (hazard ratio = 0.86; 95% CI, 0.75-0.99). Among NHB women living in redlined census tracts, we observed a slight increase in breast cancer mortality (hazard ratio = 1.13; 95% CI, 0.90-1.42); among NHW women the association was more pronounced (hazard ratio = 1.39; 95% CI, 1.09-1.78). CONCLUSIONS: These findings underscore the role of ecologic measures of structural racism on cancer outcomes. IMPACT: Place-based measures are important contributors to health outcomes, an important unexplored area that offers potential interventions to address disparities.

Race differences in cardiovascular disease and breast cancer mortality among US women diagnosed with invasive breast cancer.

BACKGROUND: Breast cancer (BC) survivors are at increased risk of cardiovascular disease (CVD) due to shared risk factors with BC and cardiotoxic treatment effects. We aim to investigate racial differences in mortality due to CVD and BC among women diagnosed with invasive BC. METHODS: Data from 407 587 non-Hispanic Black (NHB) and White (NHW) women diagnosed with malignant BC (1990-2014) were obtained from the Surveillance, Epidemiology, and End Results database. Cumulative incidence of mortality due to CVD and BC was calculated by race and age (years). Cox models were used to obtain hazard ratios (HR) and 95% confidence intervals (95%CI) for the association of race/ethnicity with cause-specific mortality. RESULTS: The 20-year cumulative incidence of CVD-related mortality was higher among younger NHBs than NHWs (e.g. age 55-69: 13.3% vs 8.9%, respectively). NHBs had higher incidence of BC-specific mortality than NHWs, regardless of age. There was a monotonic reduction in CVD-related mortality disparities with increasing age (age <55: HR = 3.71, 95%CI: 3.29, 4.19; age 55-68: HR = 2.31, 95%CI: 2.15, 2.49; age 69+: HR = 1.24, 95%CI: 1.19, 1.30). The hazard of BC-specific mortality among NHBs was approximately twice that of NHWs (e.g. age <55: HR = 1.98, 95%CI: 1.92, 2.04). CONCLUSIONS: There are substantial differences in mortality due to CVD and BC between NHB and NHW women diagnosed with invasive BC. Racial differences were greatest among younger women for CVD-related mortality and similar across age groups for BC-specific mortality. Future studies should identify pathways through which race/ethnicity affects cause-specific mortality, to inform efforts towards reducing disparities.

Disadvantaged neighborhoods and racial disparity in breast cancer outcomes: the biological link.

Neighborhoods encompass complex environments comprised of unique economic, physical, and social characteristics that have a profound impact on the residing individual's health and, collectively, on the community's wellbeing. Neighborhood disadvantage (ND) is one of several factors that prominently contributes to racial breast cancer (BC) health disparities in American women. African American (AA) women develop more aggressive breast cancer features, such as triple-negative receptor status and more advanced histologic grade and tumor stage, and suffer worse clinical outcomes than European American (EA) women. While the adverse effects of neighborhood disadvantage on health, including increased risk of cancer and decreased longevity, have recently come into focus, the specific molecular mechanisms by which neighborhood disadvantage increases BC risk and worsens BC outcomes (survivorship, recurrence, mortality) are not fully elucidated. This review illuminates the probable biological links between neighborhood disadvantage and predominantly BC risk, with an emphasis on stress reactivity and inflammation, epigenetics and telomere length in response to adverse neighborhood conditions.

Obesity and understudied minority children: existing challenges and opportunities in epidemiology.

BACKGROUND: Obesity is a major public health concern in the United States and should be addressed as early as possible, in childhood. Disparities exist in obesity prevalence and its associated comorbidities by racial/ethnic group, however less is known about the smaller racial/ethnic subclasses that are often aggregated and assumed to be homogeneously at risk. As the racial and ethnic composition of the US shifts towards greater diversity, it is important that epidemiologic research addresses these new challenges. MAIN BODY: In this short communication, we focus on Asian American children given that subgroups are historically understudied and emerging evidence among adults suggest heterogeneous associations for both obesity and cardio-metabolic outcomes. Existing limitations in this research area include: (1) identifying the appropriate measurement of adiposity in Asian American children; (2) determining high-risk cutoffs for intervention; and (3) developing strategies to ensure study robustness. CONCLUSION: Data disaggregation is a necessary approach to understand potentially heterogeneous associations in childhood obesity and cardio-metabolic risk, but epidemiologic investigators must address these challenges. Ultimately, successful strategies could help better identify high risk subgroups, target interventions, and effectively reduce the burden of obesity among American youth.

Racial Disparities in Breast Cancer Outcomes in the Metropolitan Atlanta Area: New Insights and Approaches for Health Equity.

BACKGROUND: Racial disparities in breast cancer (BC) outcomes persist where non-Hispanic black (NHB) women are more likely to die from BC than non-Hispanic white (NHW) women, and the extent of this disparity varies geographically. We evaluated tumor, treatment, and patient characteristics that contribute to racial differences in BC mortality in Atlanta, Georgia, where the disparity was previously characterized as especially large. METHODS: We identified 4943 NHW and 3580 NHB women in the Georgia Cancer Registry with stage I-IV BC diagnoses in Atlanta (2010-2014). We used Cox proportional hazard regression to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) comparing NHB vs NHW BC mortality by tumor, treatment, and patient characteristics on the additive and multiplicative scales. We additionally estimated the mediating effects of these characteristics on the association between race and BC mortality. RESULTS: At diagnosis, NHB women were younger-with higher stage, node-positive, and triple-negative tumors relative to NHW women. In age-adjusted models, NHB women with luminal A disease had a 2.43 times higher rate of BC mortality compared to their NHW counterparts (95% CI = 1.99 to 2.97). High socioeconomic status (SES) NHB women had more than twice the mortality rates than their white counterparts (HR = 2.67, 95% CI = 1.65 to 4.33). Racial disparities among women without insurance, in the lowest SES index, or diagnosed with triple-negative BC were less pronounced. CONCLUSIONS: In Atlanta, the largest racial disparities are observed in luminal tumors and most pronounced among women of high SES. More research is needed to understand drivers of disparities within these treatable features.

Comparison of Breast Cancer Risk Predictive Models and Screening Strategies for Chinese Women.

BACKGROUND: Previous studies have shown that organized mammographic screening implementation in China may not be cost-effective. Our aim was to develop a valid predictive mathematical model for selecting high-risk groups eligible for mammography examinations (MAMs) and cost-effective strategies for breast cancer screening among Chinese women. METHODS: Between 2009 and 2012, 13,355 eligible women aged 30-65 years were enrolled from the community in Chengdu City. All subjects were administered a valid questionnaire and given MAMs. Using biopsies and 1-year follow up, we compared the accuracy indexes of three predictive models (back-propagation artificial neural network [BP-ANN], logistic regression [LR], and Gail) and four serial screening strategies (BP-ANN→MAM, LR→MAM, Gail→MAM, and MAM alone). We also evaluated the benefits of the four strategies by comparing their incidence-adjusted positive predictive value (PPV). All analyses were conducted with three age-based subgroups: 30-39, 40-49, and 50-65. RESULTS: The BP-ANN1, in conjunction with additional continuous risk factor variables, was the best predictive model, with the highest sensitivity (SEN, 76.99%) and specificity (SPE, 54.20%). The BP-ANN1→MAM strategy was best for the 40-49 age group, with the highest adjusted PPV (9.80%) and reasonable SEN (81.82%). CONCLUSION: We found that the BP-ANN model performed the best and was the most accurate for predicting high risk for breast cancer among Chinese women, and the BP-ANN→MAM screening strategy was most effective among the 40-49 age group. However, mammography alone may be a sufficient screening strategy for women aged 50-65.