Tumors overexpressing the HER2 oncogene account for around 20% of breast cancer cases and are associated with aggressive disease. These tumors generally originate from a small subset of HER2 oncogene-overexpressing cells within the 3D tissue microenvironment, but little is known about the cellular interactions that occur at these early stages of disease development. There is a need to better model the earliest stages of cancer progression which requires the development of new methods to control the expression of oncogenes within a 3D tissue scaffold system. To address this challenge, this dissertation develops a new 3D ultrasound-responsive biomaterial platform and accompanying characterization techniques to model early cancer progression in cells and spheroids within 3D matrix microenvironments.