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.

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.

Screening Mammography in a Public Hospital Serving Predominantly African-American Women: A Stage-Survival-Cost Model.

BACKGROUND: Ethnic and socioeconomic disparities pervade breast cancer patterns and outcomes. Mammography guidelines reflect the difficulty in optimizing mortality reduction and cost-effectiveness, with controversy still surrounding the 2009 U.S. Preventive Services Task Force (USPSTF) recommendations. This study simulates USPSTF and American Cancer Society (ACS) guidelines' effects on stage, survival, and cost of treatment in an urban public hospital. METHODS: Charts of 274 women diagnosed with stage I, II, or III breast cancer (2008-2010) were reviewed. Published tumor doubling times were used to predict size at diagnosis under simulated screening guidelines. Stage distributions under ACS and USPSTF guidelines were compared with those observed. Cohort survival for observed and hypothetical scenarios was estimated using national statistics. Treatment costs by stage, calculated from Georgia Medicaid claims data, were similarly applied. RESULTS: Mean age at diagnosis was 56 years. African Americans predominated (82.5%), with 96% publically insured or uninsured. Simulated stages at diagnosis significantly favored ACS guidelines (43.1% stage 1/38.3% stage 2/9.9% stage 3 vs. USPSTF 23.0%/53.3 %/15.0%), as did 5-year survival and cost of treatment relative to both observed and USPSTF-predicted schema (p<.0001). Following USPSTF guidelines predicted lower survival and additional costs. CONCLUSIONS: Following ACS guidelines seems to lead to earlier diagnosis for low-income African-American women and increase 5-year survival with lower overall and breast-specific costs. The data suggest that adjusting screening practices for lower socioeconomic status, ethnic minority women may prove essential in addressing cancer disparities.

Evaluation of the Avon Foundation community education and outreach initiative Community Patient Navigation Program.

INTRODUCTION: Black women in the United States experience disproportionate breast cancer mortality. Culturally appropriate community education on the importance of breast health coupled with the availability of free or low-cost mammography screening services may help improve the use of mammography screening services among Black women. The Avon Foundation Community Patient Navigation Program seeks to fill this need. The current study presents a process and outcome evaluation of this program. METHOD: Trained and uniformed community patient navigators (PNs) host breast health education events where they recruit community members to complete a mammography interest form. Participants are referred to a nurse practitioner who determines eligibility for a free or low-cost mammogram. The community PN delivers telephone follow-up to encourage participants to make and keep their mammogram appointments. RESULTS: Over a 15-month period, 22 community PNs hosted 207 breast health events, which included 9,601 attendees. Three hundred and four participants completed a mammography interest form, and 21% of these individuals received mammograms at the collaborating health facility. Participants who reported breast symptoms were twice as likely to get a mammogram as those who did not report symptoms. DISCUSSION: Community patient navigation may be a useful resource for encouraging mammography screening among underserved women.

Metropolitan area racial residential segregation, neighborhood racial composition, and breast cancer mortality.

PURPOSE: There are significant relationships between racial residential segregation (RRS) and a range of health outcomes, including cancer-related outcomes. This study explores the contribution of metropolitan area RRS, census tract racial composition and breast cancer and all-cause mortality among black and white breast cancer patients. METHODS: This study has three units of analysis: women diagnosed with breast cancer (n = 22,088), census tracts where they lived at diagnosis (n = 1,373), and the metropolitan statistical area (MSA)/micropolitan statistical area (MiSA) where they lived at diagnosis (n = 37). Neighborhood racial composition was measured as the percent of black residents in the census tract. Metropolitan area RRS was measured using the Information Theory Index. Multilevel Cox proportional hazards models examined the association of metropolitan area RRS and census tract racial composition with breast cancer and all-cause mortality. Survival analysis explored and compared the risk of death in women exposed to environments where a higher and lower proportion of residents were black. RESULTS: Breast cancer mortality disparities were largest in racially mixed tracts located in high MSA/MiSA segregation areas (RR = 2.06, 95 % CI 1.70, 2.50). For black but not white women, as MSA/MiSA RRS increased, there was an increased risk for breast cancer mortality (HR = 2.20, 95 % CI 1.09, 4.45). For all-cause mortality, MSA/MiSA segregation was not a significant predictor, but increasing tract percent black was associated with increased risk for white but not black women (HR 1.29, 95 % CI 1.05, 1.58). CONCLUSIONS: Racial residential segregation may influence health for blacks and whites differently. Pathways through which RRS patterns impact health should be further explored.