Biomarker Analysis of Neoadjuvant Doxorubicin/Cyclophosphamide Followed by Ixabepilone or Paclitaxel in Early-Stage Breast Cancer

Abstract

Purpose: Predictive biomarkers offer the potential to improve the benefit:risk ratio of a therapeutic agent. Ixabepilone achieves comparable pathologic complete response (pCR) rates to other active drugs in the neoadjuvant setting. This phase II trial was designed to investigate potential biomarkers that differentiate response to this agent.Experimental Design: Women with untreated, histologically confirmed primary invasive breast adenocarcinoma received neoadjuvant doxorubicin/cyclophosphamide, followed by 1:1 randomization to ixabepilone (n ¼ 148) or paclitaxel (n ¼ 147). Rates of pCR were compared between treatment arms based on predefined biomarker sets: TUBB3, TACC3, and CAPG gene expression, a 20-and 26-gene expression model, MDR1 protein expression, and other potential markers of sensitivity. bIII-tubulin protein expression is reported separately but is referred to here for completeness. All patients underwent a core needle biopsy of the primary cancer for molecular marker analysis before chemotherapy. Gene expression profiling data were used for molecular subtyping.Results: There was no significant difference in the rate of pCR in both treatment arms in bIII-tubulinpositive patients. Higher pCR rates were observed among bIII-tubulin-positive patients than in bIIItubulin-negative patients. Furthermore, no correlation was evident between TUBB3, TACC3, and CAPG gene expression, MDR1 protein expression, multi-gene expression models, and the efficacy of ixabepilone or paclitaxel, even within the estrogen receptor-negative subset.Conclusion: These results indicate that bIII-tubulin protein and mRNA expression, MDR1 protein expression, TACC3 and CAPG gene expression, and multigene expression models (20-and 26-gene) are not predictive markers for differentiating treatment benefit between ixabepilone and paclitaxel in early-stage breast cancer.

SPAG5 as a prognostic biomarker and chemotherapy sensitivity predictor in breast cancer: a retrospective, integrated genomic, transcriptomic, and protein analysis

“…Full details of the study design and the patient characteristics have been described previously. 20 Out of 295 patients enrolled into the trial, 253 patients had available gene expression and pCR data. 21 Further details of the ANN approach is presented in appendix p7-10.…”

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“…279 patients with histologically-confirmed primary non-metastatic breast adenocarcinoma from phase II trial (NCT00455533) [12] were included. They all had untreated tumors of at least 2 cm in size (T2-3, N0-3) regardless of hormone receptor or HER2 expression status.…”

“…The pathological response was evaluated as the primary endpoint. A pathological complete response (CR) was defined by no histologic evidence of residual invasive adenocarcinoma in the breast and axillary lymph nodes, with or without the presence of ductal carcinoma in situ [12]. Responses were categorized as complete, partial, stabilization or progression.…”

HAGE in Triple-Negative Breast Cancer Is a Novel Prognostic, Predictive, and Actionable Biomarker: A Transcriptomic and Protein Expression Analysis

“…Residual cancer burden (RCB) was evaluated as previously described (16). Full details of the study design and patients characteristics have been described previously (17,18).…”