Models for Studying Ductal Carcinoma In Situ Progression

An estimated 55,720 new cases of ductal carcinoma in situ (DCIS) will be diagnosed in 2023 in the USA alone because of the increased use of screening mammography. The treatment goal in DCIS is early detection and treatment with the hope of preventing progression into invasive disease. Previous studies show progression into invasive cancer as well as reduction in mortality from treatment is not as high as previously thought. So, are we overdiagnosing and over-treating DCIS? An understanding of the natural progression of DCIS is paramount to address this. The purpose of this chapter is to describe various models that have been developed to simulate the processes involved in DCIS to invasive ductal carcinoma (IDC) transition. While each model possesses a unique set of strengths and weaknesses, they have collectively contributed to the current understanding of the molecular and cellular mechanisms underlying this transition. Even though much has been learned, continued advancement of the current models to best match the composition of DCIS epithelial and stromal microenvironment including the extracellular matrix (ECM), stromal cell types, and immune microenvironment will be essential. These advances will undoubtedly pave the way toward a full understanding of mechanisms associated with progression and in predicting when a DCIS lesion remains indolent and when triggers tip in the balance toward progression to malignancy.