Abstract P3-07-43: DNA methylation patterns correlating with outcome in patients treated with first-line bevacizumab for metastatic breast cancer

Abstract

Abstract Background: Biomarkers predicting response to bevacizumab containing therapy in breast cancer are of urgent need for a personalized treatment approach. DNA methylation is involved in regulation of angiogenesis and development of treatment resistance and could therefore provide predictive information for bevacizumab efficacy. Patients and methods: A genome-wide methylation profiling using the Illumina Infinium HumanMethylation450 BeadChip was performed in FFPE specimen of 36 patients with HER2-negative metastatic breast cancer treated with chemotherapy in combination with bevacizumab as first-line therapy (discovery set). Twenty-eight (78%) samples came from primary tumor and 8 (22%) from metastasis (2 lung mets., 1 pleural met., 1 liver met., 2 soft tissue mets., 1 ovarial met, 1 bone marrow infiltration). Based on progression-free survival (PFS) and breast cancer subtype (ER+ vs. triple-negative) patients were divided in responder (R) and non-responder (NR). By biostatistical methods differences in the methylation pattern between R and NR were detected. The 48 most interesting genes (e.g. because of there involvement in angiogenesis or carcinogenesis) showing a differential methylation status between R and NR are currently validated in two further metastatic breast cancer cohorts treated with (main set) and without bevacizumab (validation set), respectively. These validated results will be presented at the meeting. Citation Format: Gampenrieder SP, Rinnerthaler G, Weinhäusel A, Pulverer W, Hugnagl C, Hackl H, Romeder F, Monzo Fuentes C, Hauser-Kronberger C, Mlineritsch B, Greil R. DNA methylation patterns correlating with outcome in patients treated with first-line bevacizumab for metastatic breast cancer. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P3-07-43.