Immune Heterogeneity in Breast Cancer Natural History: Benign Breast Disease to Breast Cancer
Year: 2026
Type: article
Study design: Observational Study
Abstract: Benign breast disease (BBD), particularly lesions with atypical hyperplasia, confers an elevated risk of subsequent breast cancer; however, the majority of lesions do not progress, highlighting the need for biomarkers that distinguish indolent from high-risk disease. Emerging evidence suggests that the immune microenvironment may play a critical role in early breast carcinogenesis. We characterized immune heterogeneity across the spectrum of breast disease using Digital Spatial Profiling (DSP) of 21 immune-related proteins across 1,535 regions of interest (ROIs) from three cohorts: invasive breast cancers from the Carolina Breast Cancer Study (CBCS, n=58), a UNC BBD case series (n=20), and a Mayo Clinic BBD case–control cohort (n=177). Unsupervised clustering identified two reproducible immune states: a “High Immune” cluster enriched for adaptive immune markers and a “Quiet Immune” cluster characterized by lower immune activity. High Immune profiles predominated in tumors (77% of ROIs) but were less frequent in BBD (29% UNC; 42% Mayo). Notably, intra-lesional immune heterogeneity was substantially greater in BBD than in tumors, with over half of BBD lesions demonstrating mixed immune states across ROIs, whereas tumors more frequently exhibited immune concordance.
Source: UNC Libraries
DOI: 10.17615/y9mt-3k34
Author: Zhang, Amy
Institution: University of North Carolina at Chapel Hill
Language: English
Subfield: Cancer Research
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W7203888869
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