A cellular atlas of the preinvasive breast cancer microenvironment

Ductal carcinoma in situ (DCIS) is the most common preinvasive breast cancer, however our knowledge of the DCIS tumor microenvironment (TME) remains limited. We constructed a comprehensive atlas of the TME in estrogen-receptor positive DCIS using fresh samples collected from normal breast tissues, DCIS and invasive breast cancers. We analyzed 854,911 cells from 159 patients by single cell RNA sequencing and 39 samples by spatial transcriptomics, which identified 9 cell types and 60 cell states. Our data shows remodeling of fibroblasts, vascular and basal cells that encircle the DCIS regions and immunosuppressive ducts that support the growth of the preinvasive cancer cells. This study delineates early alterations in the DCIS TME, including many changes that persist during invasive progression.