Proliferation: the most prominent predictor of clinical outcome in breast cancer.

We recently identified a gene expression cassette of 97 unique genes that were consistently differentially expressed between low and high grade breast carcinomas. The majority of these genes were overexpressed in high grade tumors and, as expected, they were associated with cell cycle progression and proliferation. Interestingly, by applying this gene expression cassette to several datasets, we demonstrated that intermediate grade tumors were composed of a mixture of well- and poorly- differentiated tumors with statistically distinct clinical outcome similar to those of low and high grade carcinomas. Furthermore, these proliferation-related genes appear to be a common denominator of several existing prognostic gene expression signatures. This recapitulates their prognostic power far beyond the estrogen receptor (ER) status and highlights the importance of proliferation genes in breast cancer biology. Importantly, their weight seems to be far more important in ER-positive than in ER-negative disease.