A randomized, open-label, multicenter, phase II trial (NCT00455533) enrolled previously untreated women with histologically-confirmed primary invasive breast adenocarcinoma (T2–3, N0–3, M0, tumor size ≥2.0 cm), regardless of hormone receptor or HER2 expression status. Patients received sequential neoadjuvant therapy starting with 4 cycles of AC (doxorubicin 60 mg/m2 intravenously and cyclophosphamide 600 mg/m2 intravenously) given every 3 weeks, followed by 1:1 randomization to either ixabepilone (40 mg/m2 3-hour infusion) every 3 weeks for 4 cycles, or paclitaxel (80 mg/m2 1-hour infusion) weekly for 12 weeks. Fresh tumor biopsies at screening were a mandatory prerequisite for study entry for biomarker analyses. Gene expression profiling was performed by Affymetrix GeneChip to determine if pre-specified gene models could distinguish between the clinical activity of two microtubule stabilizing agents, ixabepilone and paclitaxel.
Overall design
Three core needle tumor tissue biopsies were obtained from all subjects before neoadjuvant therapy with AC and immediately combined in RNAlater® solution for subsequent RNA extraction, cRNA labeling and gene expression profiling. Pre-specified gene models were tested for their capacity to distinguish pathologic complete response rates between the AC followed by ixabepilone versus the AC followed by paclitaxel treatment regimens. All samples were collected prior to treatment. All subject received cyclophosphamide/doxorubicin (AC) prior to randomization to either Ixabepilone or Paclitaxel.
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