| Summary |
We have witnessed the rise and fall of antiangiogenic therapy in breast cancer (BC). Nevertheless, clinical remissions were observed in patients and we were interested in studying the activity of antiangiogenic drugs in BC. Inefficacy of sunitinib was observed in mouse models of metastatic BC, where evidence of enhanced metastasis was reported, and lack of efficacy of sunitinib-docetaxel combination was recently reported in a phase III clinical trial. Our aim was to understand the mechanisms and predictors of response to sunitinib in BC in a cohort of patients with untreated locally advanced or operable BC treated with an upfront window of single agent sunitinib, followed by the combination of sunitinib and docetaxel. We have used microarray profiing to monitor the transcriptional changes associated with three distinct stages of treatment: at diagnosis and prior to any treatment (t1), after an upfront window of single agent sunitinib (t2) and after the combined treatment of sunitinib and docetaxel (t3). In addtion, this microarray data also allowed us to observe the transcriptional changes associated with primary resistance to angiogenic therapy in 4 of 12 patients likely mediated by an adaptive transcriptional response to hypoxia in these resistant tumors. In BC patients this is the first demonstration of primary resistance to antiangiogenic therapy. |
