Abstract
BackgroundRecent studies have demonstrated a benefit of adjuvant capecitabine, particularly in triple negative breast cancer (TNBC) patients with residual disease after neoadjuvant chemotherapy. However, biomarkers to predict which patients are more likely to benefit from capecitabine are needed. MethodsThe NanoString Breast Cancer 360TM (BC360) and PanCancer ImmunoncologyTM (IO360) panels were used to quantify mRNA expression in TNBC samples in the FinXX trial. FinXX is a phase III trial which randomized high risk patients to receive either 3 cycles of docetaxel followed by 3 cycles of cyclophosphamide, epirubicin, and fluorouracil (Arm A: T+CEF) vs. 3 cycles of docetaxel plus capecitabine followed by 3 cycles of cyclophosphamide, epirubicin, and capecitabine (Arm B: TX+CEX). Gene signature scores were analyzed using prespecified algorithms developed by NanoString. Digital Spatial Profiling was carried out using GeoMX™ platform. A total of 111 TNBC patients were included (57 in Arm A and 54 in Arm B) with 10.2 years median follow up. ResultsThere were 7 cancer- and immune-related gene signatures identified by BC360 and IO360 panels that were significantly associated with improved recurrent free survival favoring an addition of capecitabine. These include cytotoxic cell signature, endothelial signature, mast cell signature, PDL2 gene, immunoproteasome, exhausted CD8 T-cells, and PD1. Spatially-defined analysis of protein expression of a subset of the tumor specimens using the GeoMx platform revealed biological compartment specific (Tumor and/or Stroma) differential expression of immune-related proteins in patients with improved recurrent free survival. ConclusionsAnalysis of RNA abundance signatures strongly suggests that there are important immune features that are associated with benefit from capecitabine in TNBC. However, analysis of RNA extracted from whole tumor sections lacks spatial discrimination. Using the GeoMx platform for the spatially-defined analysis of protein abundance has provided more insights and has defined specific immune features associated with improved outcome. Clinical trial identificationNCT00114816. Legal entity responsible for the studyThe authors. FundingFinnish Breast Cancer Group. DisclosureD.A. Hinerfeld: Full / Part-time employment: Nanostring. H.A. Brauer: Full / Part-time employment: Nanostring. T. Nielsen: Licensing / Royalties: Nanostring. All other authors have declared no conflicts of interest.
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