Gene expression patterns in formalin-fixed, paraffin-embedded core biopsies predict docetaxel chemosensitivity in breast cancer patients

Jenny C. Chang, Andreas Makris, M. Carolina Gutierrez, Susan G. Hilsenbeck, James R. Hackett, Jennie Jeong, Mei Lan Liu, Joffre Baker, Kim Clark-Langone, Frederick L. Baehner, Krsytal Sexton, Syed Mohsin, Tara Gray, Laura Alvarez, Gary C. Chamness, C. Kent Osborne, Steven Shak

Research output: Contribution to journalArticle

101 Scopus citations

Abstract

Previously, we had identified gene expression patterns that predicted response to neoadjuvant docetaxel. Other studies have validated that a high Recurrence Score (RS) by the 21-gene RT-PCR assay is predictive of worse prognosis but better response to chemotherapy. We investigated whether tumor expression of these 21 genes and other candidate genes can predict response to docetaxel. Core biopsies from 97 patients were obtained before treatment with neoadjuvant docetaxel (4 cycles, 100 mg/m2 q3 weeks). Three 10-μm FFPE sections were submitted for quantitative RT-PCR assays of 192 genes that were selected from our previous work and the literature. Of the 97 patients, 81 (84%) had sufficient invasive cancer, 80 (82%) had sufficient RNA for QRTPCR assay, and 72 (74%) had clinical response data. Mean age was 48.5 years, and the median tumor size was 6 cm. Clinical complete responses (CR) were observed in 12 (17%), partial responses in 41 (57%), stable disease in 17 (24%), and progressive disease in 2 patients (3%). A significant relationship (P < 0.05) between gene expression and CR was observed for 14 genes, including CYBA. CR was associated with lower expression of the ER gene group and higher expression of the proliferation gene group from the 21 gene assay. Of note, CR was more likely with a high RS (P = 0.008). We have established molecular profiles of sensitivity to docetaxel. RT-PCR technology provides a potential platform for a predictive test of docetaxel chemosensitivity using small amounts of routinely processed material.

Original languageEnglish (US)
Pages (from-to)233-240
Number of pages8
JournalBreast Cancer Research and Treatment
Volume108
Issue number2
DOIs
StatePublished - Mar 2008

Keywords

  • Docetaxel chemosensitivity
  • Paraffin-embedded material
  • Predictive markers

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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