A new study published found that chronic stressors—including perceived stress, inadequate social support, racial discrimination, and neighborhood deprivation—were associated with deleterious changes to systemic and tumor immunity in women with breast cancer, with particularly pronounced effects observed in Black women.

In the cross-sectional study, published in JAMA Network Open and conducted at two Baltimore hospitals, researchers examined 121 women (mean age = 56.27 years) with breast cancer, including 56 Black and 65 White participants. They analyzed proteomic, transcriptomic, and genomic effects associated with these stressors using 117 blood samples, 48 breast tumors, and 41 adjacent noncancerous tissues collected between February 28, 2012, to September 5, 2023.

The researchers found that higher perceived stress levels were associated with increased inflammatory markers and suppressed antitumor immunity. Specifically, stress correlated with elevated levels of pro-inflammatory cytokine interleukin-6 (beta = 0.04, 95% confidence interval [CI] = 0.01–0.07, P = .006) and multiple chemokines known to promote cancer cell invasion, including CCL4 (beta = 0.03, 95% CI = 0.0002–0.05, P = .048), CCL19 (beta = 0.03, 95% CI = 0.01–0.06, P = .02), and CCL20 (beta = 0.04, 95% CI = 0.01–0.06, P = .005).

"These data suggest that prolonged stress in patients with breast cancer may lead to an inflammatory systemic and local immune environment, suppressing an antitumor immune response and exacerbating tumor progression," the study authors wrote.

The study identified distinct immunologic features in Black women associated with stressors. These included increased chemotaxis with stress and immune suppression at the systemic level.

Black women resided in more socioeconomically deprived neighborhoods compared with White women, with a mean neighborhood deprivation index of 2.28 [2.30] among Black women compared with −0.22 [2.01] among White women. The analysis revealed that neighborhood deprivation was associated with increased levels of soluble CD83, which has been shown to inhibit T-cell function.

Notably, perceived stress was also associated with elevated tumor mutational burden, a known stimulator of tumor immunogenicity.

At the genomic level, the researchers identified 902 discrimination-associated differentially expressed genes in Black women, with enrichment in 15 discrimination-associated signaling pathways related to immune response, inflammation, and protumorigenic processes.

Lead study author Alexandra R. Harris, PhD, MPH, of the Laboratory of Human Carcinogenesis at the National Cancer Institute, and colleagues concluded: "Understanding biology as a possible mediator of cancer health disparities can inform prevention and public health interventions."

The research was supported by grant ZIA BC010887 from the Intramural Research Program of the Center for Cancer Research, National Cancer Institute, National Institutes of Health.

The authors declared having no competing interests.