Preneoplasia of the Breast and Molecular Landscape

The current model of human breast cancer progression proposes a linear multi-step process which initiates as flat epithelial atypia (FEA), progresses to atypical ductal hyperplasia (ADH), evolves into ductal carcinoma in situ (DCIS) and culminates in the potentially lethal stage of invasive ductal carcinoma. FEA commonly coexists with well-developed examples of ADH, low-grade DCIS, lobular neoplasia and tubular carcinoma. These findings and those of recent genetic studies suggest that FEA is a neoplastic lesion that may represent a precursor to or the earliest morphologic manifestation of ductal carcinoma in situ. At the same time, many of the genomic changes of ADH are also shared by common sporadic breast cancer, consistent with a high risk for future development of metachronous breast cancer.