Figure 4.

Modified Wellings Jensen model of breast cancer evolution. This figure illustrates our interpretation of the model of 'ductal' breast cancer evolution originally proposed by Wellings and Jensen [9], which was based almost entirely on the evidence of histologic continuity. In this model, hyperplastic breast epithelial cells gradually enlarge normal TDLUs to form HELUs. HELUs may then differentiate to microcysts (often with apocrine features) or progress to more complex lesions including UDH and ADH. ADH may progress to DCIS as the cells continue to proliferate and distend the acini, and DCIS may eventually progress to IBC. Progression is probably very slow overall and nonobligatory, so, for example, only a small subset of HELUs ever progress to ADH or beyond. Whether and how differentiation and progression proceed is probably dictated by the acquisition of specific genetic and epigenetic abnormalities in a largely random manner. ADH, atypical ductal hyperplasia; DCIS, ductal carcinoma in situ; HELU, hyperplastic enlarged lobular unit; IBC, invasive breast cancer; TDLU, terminal duct lobular unit; UDH, usual ductal hyperplasia.