# Neighborhood deprivation, breast cancer outcomes and stress-related gene expression in leukocytes and tumor tissue

## TL;DR

Living in a deprived neighborhood may worsen breast cancer outcomes by altering immune gene activity linked to stress and inflammation.

## Contribution

This study links neighborhood deprivation to stress-related gene expression in immune cells and tumors, offering a biological explanation for cancer disparities.

## Key findings

- Higher neighborhood deprivation was associated with increased stress-related immune gene activity in blood cells.
- Elevated stress-related gene expression in tumors was linked to worse survival in breast cancer patients.
- Stress-related immune profiles correlated with more aggressive tumor features like ER-negative status and poor differentiation.

## Abstract

Neighborhood socioeconomic deprivation is a recognized contributor to disparities in breast cancer outcomes, yet the biological mechanisms linking neighborhood context to tumor behavior remain poorly defined. The conserved transcriptional response to adversity (CTRA), characterized by upregulation of pro-inflammatory genes and downregulation of type I interferon and antibody-related genes, may represent a stress-related immune dysregulation pathway relevant to cancer aggressiveness and survival.

We examined associations among the Area Deprivation Index (ADI), CTRA gene expression profiles, tumor characteristics, and survival outcomes across two cohorts. Cohort 1 included 467 breast cancer patients treated at M.D. Anderson Cancer Center, with RNA-seq data from peripheral leukocytes used to evaluate associations of ADI with CTRA and tumor characteristics at baseline. Cohort 2 comprised 1082 TCGA breast cancer patients with RNA-seq data from tumor tissue analyzed to assess the prognostic relevance of CTRA. CTRA scores were calculated using established gene signatures. Multivariable regression and Cox proportional hazards models were applied.

In Cohort 1, higher ADI was significantly associated with elevated CTRA and pro-inflammatory gene expression in leukocytes (ρ = 0.082, p = 0.01). These immune profiles correlated with ER-negative status, stage III disease, and poor tumor differentiation. In TCGA (Cohort 2), elevated tumor CTRA expression was independently associated with worse overall survival (HR = 1.36, 95% CI: 1.04, 1.78, p = 0.02).

These findings suggest that neighborhood socioeconomic disadvantage may influence systemic immune regulation through stress-related transcriptional responses, which in turn contribute to tumor aggressiveness and survival disparities in breast cancer.

The online version contains supplementary material available at 10.1186/s13058-025-02146-y.