Contemporary model of breast cancer progression based on genetic and gene expression data. Distinct molecular events occur in normal breast epithelium giving rise to two divergent molecular pathways within which linear (denoted by vertical arrows) and horizontal (denoted by horizontal arrows) progression occurs. The first pathway is characterized by genetic alterations that include gain of 1q and loss of 16q, and this pattern of genetic alteration is seen predominantly in low grade ductal carcinoma in situ (DCIS) and invasive ductal carcinoma (IDC) and in a subset (low grade-like) of intermediate grade tumors. The second pathway is characterized by amplification of 11q13 and 17q12 in high grade tumors and 11q13 in a subset (high grade-like) of intermediate grade tumors. Additional support for the divergent two pathway model is provided by gene expression profiling data (depicted as a gene expression heatmap) generated from atypical ductal hyperplasia (ADH), DCIS and IDC. More specifically, low grade tumors express a unique set of genes that is rarely seen in high grade tumors and vice versa. Intermediate grade tumors express either 'low grade-like' gene expression signatures or 'high grade-like' gene expression signatures.