Human ductal carcinoma in situ (DCIS) represents the earliest identifiable breast cancer lesion, in which tumor cells remain confined by the architecture of the duct, surrounded on all sides by myoepithelial cells and the basement membrane, with no evidence of invasion into the surrounding stroma.It accounts for nearly 20% of new breast cancer diagnoses.The disruption of both the ME cell layer and the basement membrane is a prerequisite for tumorigenic DCIS cells to initiate invasion into the stroma.Our studies have shown that the majority of epithelial cells overlying a focally disrupted myoepithelial cell layer are estrogen receptor-alpha negative, or ERα (-) and matrix metalloproteinase-26 (MMP-26/endometase/matrilysin-2) negative.In contrast, adjacent cells within the same duct confined by an intact myoepithelial cell layer express high levels of ERα and MMP-26 and MMP-9.