Progression from a ductal carcinoma in situ (DCIS) to an invasive tumor is a major step initiating a devastating and often lethal metastatic cascade. We will discuss biological events leading to the formation of small invasive cohorts streaming from the DCIS. Using mathematical models on micro- and macro-scales integrated with information extracted from patients’ histology samples, we investigated how changes in the local microenvironmental niche near the DCIS edge enable initiation and progression of ductal microinvasions. Of particular interest are the biomechanical interactions between the cells and the ECM fiber structure, and microenvironmental features that define tumor niche prone to microinvasions.