Breast Cancer Research and Treatment

, Volume 95, Issue 3, pp 229–233

Gene expression patterns for doxorubicin (Adriamycin) and cyclophosphamide (Cytoxan) (AC) response and resistance

  • Susan Cleator
  • Anna Tsimelzon
  • Alan Ashworth
  • Mitch Dowsett
  • Timothy Dexter
  • Trevor Powles
  • Susan Hilsenbeck
  • Helen Wong
  • C. Kent Osborne
  • Peter O’Connell
  • Jenny C. Chang
Clinical Trails

DOI: 10.1007/s10549-005-9009-7

Cite this article as:
Cleator, S., Tsimelzon, A., Ashworth, A. et al. Breast Cancer Res Treat (2006) 95: 229. doi:10.1007/s10549-005-9009-7

Summary

Introduction

Doxorubicin and cyclophosphamide (Adriamycin/cytoxan, AC) is a standard chemotherapy regimen for breast cancer, but de novo resistance is frequent. We hypothesized that gene expression profiles predictive of AC response may be different from our previously published patterns with docetaxel.

Methods

Core biopsies from 40 patients were obtained before treatment with AC (6 cycles, 60/600 mg/m2q3 weeks), and clinical responses recorded after treatment. Gene expression patterns were analyzed using Affymetrix U133A chips which comprise ~22,200 genes.

Results

Clinical complete responses (cCR) were observed in 22, partial responses in 7, stable disease in 11 patients. Differential expression between sensitive cCR and resistant tumors with a low false discovery rate (<5%) was obtained. Of these 253 differentially expressed genes, pathways up-regulated in sensitive tumors included cell cycle (BUB3, CDKN1B), survival (BCL2, BAG1, BIRC1, STK39), stress response (CYP2B6, MAPK14), and estrogen-related pathways (ER, IRS1). Resistant tumors expressed gene promoting transcription (GTF3C1, ILF3), differentiation (ST14, CTNNBIP1), signal transduction (EIF1AX, EIF4EBP1), and amino acid metabolism (SRM, PLOD1, PLOD3). With leave-one-out cross validation, 67% of the samples were correctly classified, with a permutation p-value of 0.4. The previously published 92-gene molecular portrait for docetaxel sensitivity could not discriminate AC sensitivity and resistance.

Conclusions

This preliminary study supports that molecular profiles for AC response are likely to exist, with unique expression patterns for individual chemotherapy regimens. Larger validation studies are necessary to define and refine patterns for different agents.

AC chemotheraphybreast cancerpredictive markersTaxotere

Copyright information

© Kluwer Academic Publishers 2005

Authors and Affiliations

  • Susan Cleator
    • 1
  • Anna Tsimelzon
    • 2
  • Alan Ashworth
    • 1
  • Mitch Dowsett
    • 1
    • 3
  • Timothy Dexter
    • 1
  • Trevor Powles
    • 1
    • 3
  • Susan Hilsenbeck
    • 2
  • Helen Wong
    • 2
  • C. Kent Osborne
    • 2
  • Peter O’Connell
    • 4
  • Jenny C. Chang
    • 2
  1. 1.Breakthrough Breast Cancer Research CentreThe Institute of Cancer ResearchLondonUnited Kingdom
  2. 2.Breast Center and the Departments of Medicine, and Molecular and Cellular BiologyBaylor College of Medicine, and The Methodist HospitalHoustonUSA
  3. 3.The Royal Marsden HospitalLondonUnited Kingdom
  4. 4.Virginia Commonwealth University Medical CenterRichmondUSA