Progression of Early Breast Cancer to an Invasive Phenotype

Histological and molecular evidence has led to a model of breast cancer progression in which cells from the terminal duct lobular unit give rise to atypical ductal hyperplasia or atypical lobular hyperplasia, which can progress to ductal carcinoma in situ or lobular carcinoma in situ, and eventually to invasive ductal carcinoma or invasive lobular carcinoma respectively. This review will present a histomorphological and epidemiological overview of the pre-invasive stages of breast cancer progression. As there is mounting evidence that these stages are likely rough phenotypes of underlying molecular changes, current knowledge regarding changes in genetic and epigenetic features of breast cancer progression will also be discussed. Microarray and CGH-based studies will be described, which suggest that low- and high-grade breast cancers can arise from normal terminal ducts through two distinct molecular pathways. Various in vitro and in vivo models used to study the cellular and molecular changes involved in early breast cancer progression will be presented. Lastly, the specific transition from pre-invasive to invasive breast cancer will be addressed, including possible molecular predictors of the invasive phenotype and a contemporary view highlighting the involvement of the tumor microenvironment during the transition to invasive disease.