To address whether a similar differential adaptive response is observed in vivo, we examined a tumor model that recapitulates the ECM-enveloped architecture of 3D spheroids by generating ductal carcinoma in situ (DCIS)-like tumors via intraductal injection of HER2+ SUM225 breast tumor cells.2 Since HER2+ DCIS accounts for 40–60% of all patient-related DCIS cases,8–13 this model represents one of the most relevant approaches to understand the biology of HER2+ DCIS and to evaluate HER2-targeted therapies within the context of pre-neoplastic breast cancer. Here, ERBB2 is linked to breast carcinoma.