Fariba Behbod1, Jennifer H. Chen2 and Alastair Thompson3 1Department of Pathology and Laboratory Medicine, MS 3045, The University of Kansas Medical Center, Kansas City, Kansas 66160, USA 2Michael E. Debakey Department of Surgery, Baylor College of Medicine, Houston, Texas 77030, USA 3Section of Breast Surgery, Baylor College of Medicine, Co-Director, Lester and Sue Smith Breast Center, Dan L Duncan Comprehensive Cancer Center, Houston, Texas 77030, USA Correspondence: fbehbodkumc.edu; alastair.thompsonbcm.edu

Due to widespread adoption of screening mammography, there has been a significant increase in new diagnoses of ductal carcinoma in situ (DCIS). However, DCIS outcomes remain unclear. A large fraction of human DCIS (>50%) may not need the multimodality treatment options currently offered to all DCIS patients. More importantly, while we may be overtreating many, we cannot identify those most at risk of invasion or metastasis following a DCIS diagnosis. This review summarizes the studies that have furthered our understanding of DCIS pathology and mechanisms of invasive progression by using advanced technologies including spatial genomics, transcriptomics, and multiplex proteomics. This review also highlights a need for rethinking DCIS with a more focused view on epithelial states and programs and their cross talk with the microenvironment.