Inflammatory breast carcinoma signature and relapse-free survival in patients with noninflammatory breast cancer

Abstract

11048 Background: Inflammatory Breast Carcinoma (IBC) is an aggressive form of breast cancer associated with poor patient survival. We hypothesize that a gene expression profile characteristic for IBC might be related to tumour aggressiveness in nIBC. Methods: RNA from 19 IBC samples and 40 nIBC samples was hybridized onto Affymetrix chips. A gene signature predictive of IBC was identified and applied onto 7 publicly available gene expression data sets (1157 nIBC samples) with survival data of 881 nIBC samples (4 data sets). Samples were classified as “IBC-like” or “nIBC-like”. Relapse Free Survival (RFS) was compared between these groups by the Kaplan-Meyer method. We classified the 1157 nIBC breast cancer samples according to other prognostically relevant gene signatures and compared these classifications with the IBC signature classification. Cox regression analysis was performed to identify the most predictive signature with respect to RFS. Results: Patients with an “IBC-like” phenotype demonstrate a shorter RFS interval in all 4 data sets (p=0.049, p=0.032, p<0.0001, p=0.0005). Classification according to the IBC signature is significantly (p<0.0001) associated with the cell-of-origin subtypes-, the Wound Healing Response (WHR)-, the Invasive Gene Signature-, the Genomic Grade Index (GGI)- and the Fibroblastic Neoplasm Signature. Significant associations (p<0.0001) were found between the IBC signature and tumour grade and ER status. Cox regression analysis on the entire data set of 881 nIBC samples identified the IBC signature as an independent predictor of RFS (RR=1.532, C.I.=1.100–2.133, p=0.012), together with the WHR and GGI. Conclusions: We demonstrate that nIBC breast tumours having an “IBC-like” phenotype have a reduced RFS interval. This suggests that IBC and nIBC tumours demonstrate the same phenotypic traits with respect to aggressive tumour cell behaviour. Gene signatures related to tumour stroma and tumour grade add information regarding patient survival. Hence the IBC signature represents a different aspect of aggressive tumour behaviour. No significant financial relationships to disclose.