174OPredictive and prognostic value of B-cell gene-expression signatures and B-cell receptor (BCR) repertoire in HER2+ breast cancer: A correlative analysis of the CALGB 40601 clinical trial (Alliance)

Abstract Background Although tumor-infiltrating lymphocytes density is associated with increased response and improved outcomes in HER2+ breast cancer, BCR clonal diversity repertoire could provide a more informative measure of an individual’s immune-mediated anti-tumor response. In this study, we focus on the specific role of B-cell gene-expression signatures and BCR repertoire as predictive and prognostic biomarkers in CALGB 40601, a neoadjuvant study of single vs. dual (trastuzumab + lapatinib) HER2 targeting with paclitaxel. Methods Gene expression profiling by mRNA sequencing was performed on 265 pre-treatment samples and signature scores were calculated by determining the median expression of all genes in a signature. BCR repertoire analysis using V’DJer was assessed on 256 of the samples. The predictive and prognostic value of clinical parameters, signature scores and BCR diversity metrics was tested in a univariate analysis for pathologic complete response (pCR) and event-free survival (EFS). Results Of the >600 expression signatures tested, 10 were significantly associated with both pCR and EFS. Five immune-related signatures were associated with higher pCR and better outcome: a T-helper signature (OR = 5.1, HR = 0.22, both p