Abstract P1-08-07: High tumor CD68 mRNA content (intratumoral macrophages) predicts response to neoadjuvant chemotherapy

Abstract

Abstract Background Immune cell infiltrates have been shown to play a prominent role with regard to prognosis of node negative breast cancer (Schmidt et al 2008). Moreover, it has been shown that B-cells and T-Cells are of particular importance for the response to chemotherapy (Schmidt et al. 2012). However, the role of macrophages remains unclear. It has been assumed, that tumor-associated macrophages play a role in promoting tumorigenesis. Still their role with regard to therapy prediction is unknown. Here we tested wether the infiltration of macrophages is associated with the response to neoadjuvant chemotherapy. Materials and Methods Pretreatment core cut biopsies from n = 100 patients with PBC treated within a randomized phase II trial (1) of anthracyline/taxane based NAC were examined. RNA from formalin-fixed, paraffin embedded (FFPE) routine biopsies were extracted using a bead-based extraction method (STRATIFYER XTRAKT kits). CD68 and ESR1, PGR, HER2, Ki67 as well as CALM2 as a house keeping gene were measured via a multiplex quantitative RT-PCR (RT-qPCR). Correlation analyses and partitioning tests were performed using the SAS JMP® 9.0.0 software. Results CD68 mRNA exhibited a normal data distribution (Median expression 40-DCT 34,66) in the core needle biopsies of advanced breast tumors. CD68 mRNA correlated strongly with Ki67 mRNA levels (Spearman r = 0,46; p<0,001), whereas there is virtually no correlation with other classical biomarkers such as ESR1, PGR and HER2. Partitioning analysis revealed that CD68 mRNA levels are superior to the previously and prospectively validated response markers ESR1 mRNA and HER2 mRNA. When using the median mRNA expression as an objective cut-off measurement no tumor having low CD68 mRNA expression did respond to chemotherapy, while 22% of the CD68 positive tumors responded by pathological complete response (ypT0ypN0). Based on molecular subtyping into Luminal, HER2 positive and Triple-Negative with predefined Cut-Off values for ESR1mRNA and HER2 mRNA levels, high CD68 were particularly informative within luminal tumors (22% pCR versus 0% pCR rate) and Triple negative tumors (38% pCR versus 0% pCR rate). Conclusion The presence of macrophages indicates tumors being sensitive to chemotherapy beyond the prospectively validated ESR1 and HER2 mRNA determinations (2), both in luminal and triple negative tumors. The mRNA expression levels of CD68 provide additional information beyond conventional subtyping and might therefore be useful for early assessment of non-response to chemotherapy und subsequent treatment planning. 1) Schneeweiss et al, Ann Oncol 2011 2) Denkert et al, Ann Oncol 2013. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P1-08-07.