Historical Redlining, Persistent Mortgage Discrimination, and Race in Breast Cancer Outcomes.

Importance: Inequities created by historical and contemporary mortgage discriminatory policies have implications for health disparities. The role of persistent mortgage discrimination (PMD) in breast cancer (BC) outcomes has not been studied. Objective: To estimate the race-specific association of historical redlining (HRL) with the development of BC subtypes and late-stage disease and a novel measure of PMD in BC mortality. Design, Setting, and Participants: This population-based cohort study used Georgia Cancer Registry data. A total of 1764 non-Hispanic Black and White women with a BC diagnosis and residing in an area graded by the Home Owners' Loan Corporation (HOLC) in Georgia were included. Patients were excluded if they did not have a known subtype or a derived American Joint Committee on Cancer stage or if diagnosed solely by death certificate or autopsy. Participants were diagnosed with a first primary BC between January 1, 2010, to December 31, 2017, and were followed through December 31, 2019. Data were analyzed between May 1, 2022, and August 31, 2023. Exposures: Scores for HRL were examined dichotomously as less than 2.5 (ie, nonredlined) vs 2.5 or greater (ie, redlined). Contemporary mortgage discrimination (CMD) scores were calculated, and PMD index was created using the combination of HRL and CMD scores. Main Outcomes and Measures: Estrogen receptor (ER) status, late stage at diagnosis, and BC-specific death. Results: This study included 1764 women diagnosed with BC within census tracts that were HOLC graded in Georgia. Of these, 856 women (48.5%) were non-Hispanic Black and 908 (51.5%) were non-Hispanic White; 1148 (65.1%) were diagnosed at 55 years or older; 538 (30.5%) resided in tracts with HRL scores less than 2.5; and 1226 (69.5%) resided in tracts with HRL scores 2.5 or greater. Living in HRL areas with HRL scores 2.5 or greater was associated with a 62% increased odds of ER-negative BC among non-Hispanic Black women (odds ratio [OR], 1.62 [95% CI, 1.01-2.60]), a 97% increased odds of late-stage diagnosis among non-Hispanic White women (OR, 1.97 [95% CI, 1.15-3.36]), and a 60% increase in BC mortality overall (hazard ratio, 1.60 [95% CI, 1.17-2.18]). Similarly, PMD was associated with BC mortality among non-Hispanic White women but not among non-Hispanic Black women. Conclusions and Relevance: The findings of this cohort study suggest that historical racist policies and persistent discrimination have modern-day implications for BC outcomes that differ by race. These findings emphasize the need for a more nuanced investigation of the social and structural drivers of disparate BC outcomes.

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.

Time to Surgical Treatment and Facility Characteristics as Potential Drivers of Racial Disparities in Breast Cancer Mortality.

BACKGROUND: Black women are more likely to die of breast cancer than White women. This study evaluated the contribution of time to primary surgical management and surgical facility characteristics to racial disparities in breast cancer mortality among both Black and White women. METHODS: The study identified 2224 Black and 3787 White women with a diagnosis with stages I to III breast cancer (2010-2014). Outcomes included time to surgical treatment (> 30 days from diagnosis) and breast cancer mortality. Odds ratios (ORs) and 95% confidence intervals (CIs) associating surgical facility characteristics with surgical delay were computed, and Cox proportional hazards regression was used to compute hazard ratios (HRs) and 95% CIs associating delay and facility characteristics with breast cancer mortality. RESULTS: Black women were two times more likely to have a surgical delay (OR, 2.15; 95% CI, 1.92-2.41) than White women. Racial disparity in surgical delay was least pronounced among women treated at a non-profit facility (OR, 1.95; 95% CI, 1.70-2.25). The estimated mortality rate for Black women was two times that for White women (HR, 2.00; 95% CI, 1.83-2.46). Racial disparities in breast cancer mortality were least pronounced among women who experienced no surgical delay (HR, 1.81; 95% CI, 1.28-2.56), received surgery at a government facility (HR, 1.31; 95% CI, 0.76-2.27), or underwent treatment at a Commission on Cancer-accredited facility (HR, 1.82; 95% CI, 1.38-2.40). CONCLUSIONS: Black women were more likely to experience a surgical delay and breast cancer death. Persistent racial disparities in breast cancer mortality were observed across facility characteristics except for government facilities.

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.

Racial Disparities in Diagnostic Delay Among Women With Breast Cancer.

PURPOSE: Early diagnosis is fundamental to reducing breast cancer (BC) mortality, and understanding potential barriers from initial screening to confirmed diagnosis is essential. The aim of this study was to evaluate patient characteristics that contribute to delay in diagnosis of screen-detected cancers and the contribution of delay to tumor characteristics and BC mortality. METHODS: Three hundred sixty-two White and 368 Black women were identified who were screened and received subsequent BC diagnoses within Emory Healthcare, a part of Emory University health care system (2010-2014). Multivariable-adjusted logistic regression was used to calculate the odds ratios (ORs) and 95% confidence intervals (CIs) associating patient characteristics with delay to diagnostic evaluation (≥30 versus <30 days), delay to biopsy (≥15 versus <15 days), and total delay (≥45 versus <45 days). Additionally, the ORs and 95% CIs associating delay with tumor characteristics and BC mortality were computed. RESULTS: Black women and women diagnosed at later stages, with larger tumor sizes, and with triple-negative tumors were more likely to experience ≥45 days to diagnosis. In multivariable-adjusted models, Black women had at least a two-fold increase in the odds of delay to diagnostic evaluation (OR, 1.98; 95% CI, 1.45-2.71), biopsy delays (OR, 2.41; 95% CI, 1.67-3.41), and total delays ≥45 days (OR, 2.22; 95% CI, 1.63-3.02) compared with White women. A 1.6-fold increased odds of BC mortality was observed among women who experienced total delays ≥45 days compared with women without delays in diagnosis (OR, 1.57, 95% CI, 0.96-2.58). CONCLUSIONS: The study demonstrated racial disparities in delays in the diagnostic process for screen-detected malignancies. Total delay in diagnosis was associated with an increase in BC mortality.

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.

Targeted nanoparticles for image-guided treatment of triple-negative breast cancer: clinical significance and technological advances.

Effective treatment of triple-negative breast cancer (TNBC) with its aggressive tumor biology, highly heterogeneous tumor cells, and poor prognosis requires an integrated therapeutic approach that addresses critical issues in cancer therapy. Multifunctional nanoparticles with the abilities of targeted drug delivery and noninvasive imaging for monitoring drug delivery and responses to therapy, such as theranostic nanoparticles, hold great promise toward the development of novel therapeutic approaches for the treatment of TNBC using a single therapeutic platform. The biological and pathological characteristics of TNBC provide insight into several potential molecular targets for current and future nanoparticle-based therapeutics. Extensive tumor stroma, highly proliferative cells, and a high rate of drug resistance are all barriers that must be appropriately addressed in order for these nanotherapeutic platforms to be effective. Utilization of the enhanced permeability and retention effect coupled with active targeting of cell surface receptors expressed by TNBC cells, and tumor-associated endothelial cells, stromal fibroblasts, and macrophages is likely to overcome such barriers to facilitate more effective drug delivery. An in-depth summary of current studies investigating targeted nanoparticles in preclinical TNBC mouse and human xenograft models is presented. This review aims to outline the current status of nanotherapeutic options for TNBC patients, identification of promising molecular targets, challenges associated with the development of targeted nanotherapeutics, the research done by our group as well as by others, and future perspectives on the nanomedicine field and ways to translate current preclinical studies into the clinic.