Abstract P3-12-01: Serum biomarkers identification using quantitative proteomics in patients (pts) with untreated brain metastases from HER2-positive breast cancer receiving capecitabine (C) and lapatinib (L) (UNICANCER LANDsCAPE trial)

Background: The LANDsCAPE phase II study showed that C+L had a significant antitumor activity in previously untreated brain metastases (BM) from HER2-positive breast cancer (BC), with a central nervous system-objective response rate (CNS-ORR) of 67% and a median time to whole-brain radiotherapy (WBRT) of 8.3 months (43 analysed pts). Thus initial C+L combination might be a viable alternative to immediate WBRT in this setting. In this study, serum samples were collected before and during treatment for proteomic-based approaches to identify predictive biomarkers of treatment response. Methods: Baseline (BL) and day 21 (D21) serum samples from highly responsive (R, CNS lesions -volumetric response ≥ 75%, n=6) and non-responsive (NR, CNS-stable or progressive disease, n=6) pts were subjected to isobaric Tag for Relative and Absolute Quantification (iTRAQ)-based proteomics. Samples from each condition were pooled to constitute 4 independent mixes ((BL-R, D21-R, BL-NR and D21-NR). Each of them underwent immuno-depletion of highly abundant proteins, concentration, reduction, alkylation and tryptic digestion. Then, each mix was fractionated and subjected to iTRAQ identification and quantitation using nano-liquid chromatography (LC) and electrospray ionisation (ESI)-orbitrap tandem mass spectrometry (MS/MS) (LTQ-orbitrap, Thermofisher). Differentially expressed proteins were analysed using IPA (Ingenuity® Systems) to highlight biological functions and signalling pathways that were most significantly enriched. Results: iTRAQ-based measurements identified serum proteins with significant (fold-change > 1.5 and p-value Conclusion: iTRAQ-based quantitative proteomics identify serum proteins that could predict the therapeutic response to C+L combination in untreated BM from HER2-positive BC. If validated, such biomarkers may help to select the best therapeutic strategy in this setting. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P3-12-01.