Development of cancer requires the mechanical and bio-physiological changes through its initial state to the malignant state. It has attracted enormous attention from researchers in cancer research and prompted them to closely examine the interaction of cancer cells with their surrounding microenvironment. Of particular interest in this area has been in delineating the effects of the composition and biomechanical properties of stromal connective tissue on the biology of cancer cells. These studies, however, have been greatly challenged by the lack of experimental models that provide the capability to recapitulate the complexity of malignant tumor development and progression in the mammary duct. Although considerable progress has been made in three-dimensional (3D) culture of breast cancer cells, these models are limited in their ability to replicate the complex structure of the mammary duct and surrounding stromal tissue containing multiple types of specialized cells. Consequently, the study of breast cancer research has been dependent predominantly on animal models.As a first step towards resolving these critical technical challenges, we have developed a microengineered model of human breast that recapitulates the structural complexity of the mammary duct. Specifically, engineering of microchannels made of poly(dimenthylsiloxane) (PDMS), vitrified membranes fabricated the compartmentalized micro-spaces and multi-layered structure of mammary duct was incarnated by co-culturing human mammary epithelial cells and mammary fibroblast cells in biomimetic 3D hybrid structure. Moreover, ductal carcinoma in situ (DCIS) cells of breast were cultivated in a spheroid shape and merged inside the epithelial cell layer for the generation of breast cancer cell embedded microenvironment.We believe that our system will provide the opportunity to faithfully model the key processes of breast cancer progression and metastasis, and make a significant contribution to elucidating their underlying mechanisms, which may permit the identification of new therapeutic.