Abstract

Women of Afro-Caribbean descent confront more aggressive breast cancer subtypes at a younger age than their Caucasian counterparts. Yet, breast cancer research and treatment development have predominantly focused on Caucasian populations, neglecting potential biological drivers of these disparities. Our study addresses this gap by in-depth characterising the breast tumour microenvironment (TME) in an ethnically diverse cohort. We analysed treatment-naïve breast cancer samples from 45 Black British and 45 White British women, matched by age, tumour subtype, and stage by employing spatial transcriptomics (NanoString GeoMx) and hyper-plex protein profiling (Leica Microsytems Cell DIVE ). We captured whole-transcriptome data from cancer (PanCK+), immune (CD45+), and stromal (aSMA+) compartments from both tumour centre and tumour edge. The most striking differences emerged within the immune and stromal compartments, not in the cancer cells, underscoring metabolic, adhesion, and extracellular matrix rewiring in Black British tumours. Complementary spatial protein profiling further revealed changes in tissue architecture with distinct recurrent patterns of cellular organisation and cell-cell interactions, involving endothelial and B-cells. Our findings suggest that the TME plays a pivotal role in driving ethnic disparities in breast cancer, highlighting the urgent need for ethnically tailored therapies and more inclusive clinical trials to advance precision cancer care. This breakthrough offers new avenues for improving overall outcomes in breast cancer.