The tumor microenvironment (TME) is important for cancer growth and progress. Whereas angiogenesis is an established hallmark of cancer, the field of cancer neuroscience is now emerging. Here, we asked whether neurogenesis and angiogenesis are associated features in breast cancer and related to aggressive behavior. Single cell-based spatial analysis by imaging mass cytometry (IMC) indicated significant colocalization of neural and vascular structures, suggesting the presence of neuro-vascular niches within the tumor tissue. By protein and gene expression data from human breast cancer cohorts, we found that neurogenesis and angiogenesis, together with a consolidated neuro-angiogenic signature score, were linked to high-grade breast cancer characteristics and reduced survival, also within the luminal tumor subgroup. Cases with high neuro-angiogenic score were split in two subgroups, one hormone receptor negative and one receptor positive. Our findings might be relevant for improved patient stratification and further exploration of novel treatment strategies.
