Abstract
BACKGROUND: The identification of molecular features characterizing metastatic disease is a critical area of oncology research, as metastatic foci often exhibit distinct biological behaviors compared to primary tumors. While the focus has largely been on the neoplastic cells themselves, the characterization of the associated stroma remains largely underexplored, with significant implications for understanding metastasis. MAIN BODY: By employing spatially resolved transcriptomics, we analyzed the transcriptional features of primary breast adenocarcinoma and its associated metastatic foci, on a representative set of microregions. We identified a stromal metastatic (Met) signature, which was subsequently validated across transcriptomic reference human breast cancer (BC) datasets and in spatial transcriptomics of a murine model. CONCLUSION: We discuss the potential of a stromal Met signature to pinpoint metastatic breast cancer, serving as a prognostic tool that can provide a foundation for the exploration of tumor-extrinsic molecular hallmarks of BC metastatic foci.