Breast cancer is one of the most common malignancies among women in the western world. In the last two decades, major advances have been made in our understanding of breast cancer that have resulted in a decline in breast cancer mortality. To advance these improvements, research efforts need to be directed to a series of areas, including breast cancer genetics and identification of new targets for therapy.Accordingly, the proposed research aims to characterize mammary cells during different stages of carcinogenesis, targeted treatment and during their dormant period that might lead to tumor relapse:• We will delineate cooperating lesions in breast cancer to develop better strategies for targeted therapy.• Our approach to understand the origin of tumor initiating cells and how and why they differ from normal breast stem cells will open new avenues in tumor treatment and prevention.• Characterization of the residual cells after treatment will greatly improve our understanding of the mechanisms of oncogene dependence and may lead to more effective therapeutic strategies to prevent breast cancer relapse.To investigate these objectives, we will utilize tractable in vivo mouse mammary tumor models in parallel with 3D cell culture systems of primary mammary cells derived from these animals. This novel, combined approach allows to retrieve more detailed mechanistic insights with respect to cellular organization, position and fate of specialized cells within a mammary acinus and -at the same time- to follow the in vivo model for overall phenotypes.The EMBL Mouse Biology Unit offers me the unique chance to implement these novel approaches in the European Research Area (ERA). Employment of sophisticated 3D cell culture systems in combination with transgenic mouse models, are expensive. The FP7-PEOPLE-2011-CIG award will contribute to address the outlined objectives and will allow to perform experiments that we view as a potent preclinical approach.