P2-12-11: Clinical Relevance of a IL-8/B-Cell Gene Signature Identified from Triple Negative Breast Cancer (TNBC) in Intrinsic Breast Cancer Subtypes.

Abstract

Background: As presented recently (SABCS 2010, #S5-5) a ratio of high B-cell and low IL-8 metagenes using gene expression analysis identified 32 % of triple negative breast cancers with good prognosis and was the only significant predictor in multivariate analysis including routine clinicopathological variables. However, the clinical relevance of this signature within the intrinsic breast cancer subtypes still remains unclear and is analyzed here. Methods: Affymetrix gene expression data from n=2417 breast cancer patients have been assembled. We performed an unsupervised analysis to define metagenes that distinguish molecular subsets within TNBC (SABCS 2010, #S5-5). A high expression of B- cell metagenes was associated with good and high expression of IL-8-related metagenes were associated with poor prognosis. To identify intrinsic subtypes we used the method previously described by Hu et al. (2006) and the prognostic value within those subtypes was assessed by analyzing the event free survival of patients as function of high and low B-cell/IL-8 metagene ratio. Results: Comparing ER positive with ER negative patients the B-ceh7LL-8 ratio showed only in ER negative breast cancer a significant prognostic value (log rank p-value <.0001). Within the entire cohort 37.8 % of patients could be assigend to luminal A, 35.2 % to luminal B, 7,4 % to erbB2 and 19.6 % to basal-like subtypes. Event free survival of patients with good or poor B-cell/IL-8 ratio showed only in basal-like breast cancer patients a statistical significant difference (p<.0001). However, we could not observe any difference in prognosis in luminal A and B, as well as erbB2 tumors. No difference in the expression of the proliferation metagene was observed when samples of the intrinsic subtypes were stratified according to the prognostic predictor based on high expression of the B-Cell metagene and low expression of the IL-8 metagene. Conclusion: The B-cell/IL-8 ratio is highly prognostic in basal-like/TNBC and shows no association with proliferation status. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P2-12-11.