Abstract B094: Neighborhood deprivation and transcriptomic markers of accelerated biological aging among Black and white women with breast cancer

Abstract

Neighborhood deprivation is a well-documented contributor to racial disparities in breast cancer mortality, but the distinct pathways by which the residential social environment becomes biologically embedded in breast tumors remain poorly defined. Accelerated biological aging, characterized by cellular senescence, DNA damage, and the senescence-associated secretory phenotype (SASP), is a candidate mechanism linking chronic social adversity to aggressive tumor phenotypes. In this study, we examined the association between neighborhood deprivation and transcriptomic markers of accelerated aging in breast tumors, overall and stratified by race and estrogen receptor (ER) status. We identified non-Hispanic Black (NHB) and non-Hispanic white (NHW) women diagnosed with a first primary, stage I–III breast cancer, 21 years or older, and who consented to have their tumor tissue used for research. Residential address at diagnosis was geocoded to the census tract level and linked to the Neighborhood Deprivation Index (NDI). We categorized NDI into tertiles (Q1, least deprived, referent). Tumor RNA sequencing was used to derive four previously derived markers of accelerated biological aging: 1) p16INK4a expression, 2) a DNA damage response (DDR) signature, 3) the SASP, and 4) SenMayo, a gene list reflecting intracellular changes specific to senescent immune cells. Associations between NDI tertile and each transcriptomic marker were estimated using multivariable linear regression adjusted for age and race, and additionally for BMI, smoking, education, and family history. We ran complete-case analyses and used missing data imputation to account for missing data on covariates. We identified 215 women with breast cancer, of whom 158 (80 NHB, 78 NHW) had tumor RNAseq passing quality control and comprised the analytic sample. Overall, higher NDI was associated with lower p16INK4a expression. Compared with women residing in the least deprived neighborhoods (Q1), women residing in Q2 and Q3 had lower p16INK4a expression (Q2: β= −0.77, 95%CI −1.23, −0.32; Q3: β=−0.51, 95%CI −0.99, −0.03). In contrast, higher neighborhood deprivation was associated with consistently elevated, although imprecise, estimates of SASP (Q2 β=5.68, 95%CI −3.80, 15.1; Q3 β=6.39, 95%CI −3.64, 16.4) and SenMayo (Q2 β=8.47, 95%CI 8.47, 95%CI −8.37, 25.3; Q3 β=5.55, 95%CI −12.3, 23.4) expression—two markers of pro-inflammatory senescence programming—whereas associations with DDR estimates were near null. In race-stratified analyses, the associations with p16INK4a, SASP, and SenMayo were similar for NHW women as the overall analyses. Among NHB women, the associations were similar, but attenuated. NDI was associated with transcriptomic signatures of accelerated biological aging in breast tumors, with differences by race and ER status, although estimates were imprecise. Findings may suggest that the residential social environment may relate to distinct molecular programs, but additional studies are necessary to understand and verify findings. Lindsay J. Collin, Yinxian Chen, Lauren E. Barber, Lauren E . McCullough, Jasmine M. Miller-Kleinhenz. Neighborhood deprivation and transcriptomic markers of accelerated biological aging among Black and white women with breast cancer [abstract]. In: Proceedings of the 19th AACR Conference on the Science of Cancer Health Disparities; 2026 Oct 18-21; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2026;35(10 Suppl):Abstract nr B094.