Gene expression panel (TheraPrint) analyzed as predictors of response to neoadjuvant chemotherapy (NCT) in patients (pts) with stage II-III and inflammatory breast cancer (BC).

Abstract

8 Background: TheraPrint is a microarray-based gene expression panel of 125 genes identified as potential targets for prognosis and therapeutic response. These genes may hold the key to a greater level of personalized prognosis and therapy for BC pts. The aim of the current study was to assess the clinical relevance of the TheraPrint genes for either predictive and/or prognostic value in two patient cohorts treated with NCT. Methods: The 1st patient cohort are 68 Stage II-III BC pts treated with NCT. Expression data from Agilent full genome arrays, containing the MammaPrint, BluePrint and TheraPrint diagnostic profiles/probes (Somlo et al, 2009). Median FU 2.3 years. The 2nd patient cohort are 230 Stage I-III BC pts treated with NCT. Expression data from Affymetrix probe sets was publically available (Iwamoto et al, 2011). Median FU 5.2 years. To identify genes that are differentially expressed between responders (pCR/RCBI) and non-responders, a supervised analysis was performed. The analysis was performed across all pts and also within groups of HER2+ and HER2-. Univariate t-tests were performed, with results filtered by permutation p-value (p<0.05) and fold change of >1.5. Global test was also reported. In addition, survival data analysis was performed across all pts. Results: Overlapping genes between the 2 datasets that were significantly differentially expressed between responders and non-responders include: BCL2 (down-regulated) and CDH3, GRB7, KRT6B, KRT17 (up-regulated). When analysing the HER2- subgroup, 3 genes turned out to be differentially expressed between responders and non-responders in the 2 datasets: FLT1, PIK3R1 (down-regulated) and KRT6B (up-regulated). For the HER2+ subgroup, only one gene overlapped for the 2 datasets: IL2RA (up-regulated). The top canonical pathways for the significant genes have been analyzed, and in addition correlation of the TheraPrint gene expression with survival for these pt groups. Conclusions: This study has identified several genes from a panel of 125 TheraPrint genes with statistically significant correlation between expression and response to NCT.