A RB-1 loss of function gene-signature (RBsig) as a tool to predict response to neoadjuvant chemotherapy (CT) plus anti-HER2 agents (H): A substudy of the NeoALTTO trial (BIG 1-06).

570Background: CT added to H is the treatment of choice in HER2+ early breast cancer (BC) patients (pts). However HER2+ tumors are clinically and biologically heterogeneous and treatment response varies significantly by hormone receptor (HR) status and molecular subtype. Predictive biomarkers are needed in this context. We have previously shown that RBsig expression correlates with pathological complete response (pCR) rate following CT +/− H in ER+/HER2+ BC pts within a metadataset of 10 neoadjuvant clinical trials. The present study assessed whether RBsig is predictive of response to neoadjuvant CT in combination with H, within the NeoALTTO trial. Methods: We collected RNA-sequencing data from pre-treatment biopsies derived from NeoALTTO, a trial randomizing pts with HER2+ early BC to receive lapatinib, trastuzumab or both together with weekly paclitaxel. RBsig expression was computed retrospectively and correlated with pCR using receiving-operating characteristic (ROC) curves.The RBsig was dichotomized ...