Linking pBRD4 and PP2A inhibition in triple negative breast cancer.

e13011Background: It has been recently reported that triple negative breast cancer (TNBC) cells show a preferential sensitivity to BET bromodomain inhibitors (BBI). Moreover, BRD4 hyperphosphorylation was identified as an alteration that confers resistance to BET bromodomain inhibition and PP2A as a main phosphatase that regulates BRD4 phosphorylation levels. However, both PP2A activation status and clinical significance of BRD4 phosphorylation in TNBC remain to be investigated. We report here that BRD4 hyperphosphorylation is a common event that defines a subgroup of TNBC patients with very poor outcome. Methods: We analyzed here BDR4 phosphorylation status in a cohort of 126 TNBC patients, observing BRD4 hyperphosphorylation in 35.4% of cases (44/126). Interestingly, this alteration was found associated with higher tumor grade (p = 0.020) and with the subgroup of cases who relapsed (p = 0.005). Results: Moreover, high BDR4 phosphorylation determined significantly shorter overall (8.5 vs. 22.7 months; p ...