On Apr. 29, 2008, National Cancer Institute (NCI) researchers identified a pattern of gene activity in mice that may help to predict individual risk for breast cancer metastasis and survival in humans. A single gene called bromodomain 4 (Brd4) regulates the expression of this pattern, also called a signature. The researchers found that one result of this Brd4 regulation is the suppression of tumor growth and metastasis in a mouse model of cancer.

However, a dramatic reduction of tumor growth and pulmonary metastasis was observed after s.c. implantation into mice, implying that activation of Brd4 may somehow be manipulating response to tumor microenvironment in the in vivo setting. Further in vitro analysis shows that Brd4 modulates extracellular matrix gene expression, a class of genes frequently present in metastasis-predictive gene signatures. Microarray analysis of the mammary tumor cell lines identified a Brd4 activation signature that robustly predicted progression and/or survival in multiple human breast cancer datasets analyzed on different microarray platforms.

Intriguingly, the Brd4 signature also almost perfectly matches a molecular classifier of low-grade tumors. Taken together, these data suggest that dysregulation of Brd4-associated pathways may play an important role in breast cancer progression and underlies multiple common prognostic signatures.