Skip to main content

Advertisement

SpringerLink
Log in

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

  • Clinical Trial
  • Published:
Breast Cancer Research and Treatment Aims and scope Submit manuscript

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. EBCTG (1998) Polychemotherapy for early breast cancer: an overview of the randomised trials. Lancet 352:930–942

    Article  Google Scholar 

  2. The Early Breast Cancer Trialists’ Collaborative Group E (1998) Tamoxifen for early breast cancer: an overview of the randomised trials. Lancet 351(9114):1451–1467

    Article  Google Scholar 

  3. Hortobagyi G (1997) Docetaxel in combined modality therapy for breast cancer. Oncology 11(6):9–10

    Google Scholar 

  4. Henderson IC, Berry D, Demetri G et al. (1998) Improved disease free survival and overall survival from the addition of sequential paclitaxel but not from escalation of doxorubicin in the adjuvant chemotherapy of patients with node-positive primary breast cancer. Proc Am Soc Clin Onco 17:101

    Google Scholar 

  5. Fisher B, Bryant J, Wolmark N, Mamounas E, Brown A, Fisher ER, Wickerham DL, Begovic M, DeCillis A, Robidoux A et al (1998) Effect of preoperative chemotherapy on the outcome of women with operable breast cancer. J Clin Oncol 16(8):2672–2685

    PubMed  CAS  Google Scholar 

  6. Bear HD, Anderson S, Smith RE, Geyer CE Jr, Mamounas EP, Fisher B, Brown AM, Robidoux A, Margolese R, Kahlenberg MS et al (2006) Sequential preoperative or postoperative docetaxel added to preoperative doxorubicin plus cyclophosphamide for operable breast cancer: national surgical adjuvant breast and bowel project protocol B-27. J Clin Oncol 24(13):2019–2027

    Article  PubMed  CAS  Google Scholar 

  7. Bear HD, Anderson S, Brown A, Smith R, Mamounas EP, Fisher B, Margolese R, Theoret H, Soran A, Wickerham DL et al (2003) The effect on tumor response of adding sequential preoperative docetaxel to preoperative doxorubicin and cyclophosphamide: preliminary results from national surgical adjuvant breast and bowel project protocol B-27. J Clin Oncol 21(22):4165–4174

    Article  PubMed  CAS  Google Scholar 

  8. Chang J, Powles TJ, Allred DC, Ashley SE, Clark GM, Makris A, Assersohn L, Gregory RK, Osborne CK, Dowsett M (1999) Biologic markers as predictors of clinical outcome from systemic therapy for primary operable breast cancer. J Clin Oncol 17(10):3058–3063

    PubMed  CAS  Google Scholar 

  9. Tham YL, Gomez LF, Mohsin S, Gutierrez MC, Weiss H, Hilsenbeck SG, Elledge RM, Chamness GC, Osborne CK, Allred DC et al (2005) Clinical response to neoadjuvant docetaxel predicts improved outcome in patients with large locally advanced breast cancers. Breast Cancer Res Treat 94(3):279–284

    Article  PubMed  CAS  Google Scholar 

  10. Chang JC, Wooten EC, Tsimelzon A, Hilsenbeck SG, Guiterrez MC, Elledge RM, Mohsin S, Osborne CK, Chamness GC, Allred DC et al (2003) Gene expression profiling predicts therapeutic response to docetaxel (Taxotere(tm)) in breast cancer patients. Lancet 362:280–287

    Article  Google Scholar 

  11. Ayers M, Symmans WF, Stec J, Damokosh AI, Clark E, Hess K, Lecocke M, Metivier J, Booser D, Ibrahim N et al (2004) Gene expression profiles predict complete pathologic response to neoadjuvant paclitaxel and fluorouracil, doxorubicin, and cyclophosphamide chemotherapy in breast cancer. J Clin Oncol 22(12):2284–2293

    Article  PubMed  CAS  Google Scholar 

  12. Paik S, Shak S, Tang G, Kim C, Baker J, Cronin M, Baehner FL, Walker MG, Watson D, Park T et al (2004) A multigene assay to predict recurrence of tamoxifen-treated, node-negative breast cancer. N Engl J Med 351(27):2817–2826

    Article  PubMed  CAS  Google Scholar 

  13. Habel LA, Shak S, Jacobs MK, Capra A, Alexander C, Pho M, Baker J, Walker M, Watson D, Hackett J et al (2006) A population-based study of tumor gene expression and risk of breast cancer death among lymph node-negative patients. Breast Cancer Res 8(3):R25

    Article  PubMed  Google Scholar 

  14. Paik S, Tang G, Shak S, Kim C, Baker J, Kim W, Cronin M, Baehner FL, Watson D, Bryant J et al (2006) Gene expression and benefit of chemotherapy in women with node-negative, estrogen receptor-positive breast cancer. J Clin Oncol 24(23):3726–3734

    Article  PubMed  CAS  Google Scholar 

  15. Gianni L, Zambetti M, Clark K, Baker J, Cronin M, Wu J, Mariani G, Rodriguez J, Carcangiu M, Watson D et al (2005) Gene expression profiles in paraffin-embedded core biopsy tissue predict response to chemotherapy in women with locally advanced breast cancer. J Clin Oncol 23(29):7265–7277

    Article  PubMed  CAS  Google Scholar 

  16. Cronin M, Pho M, Dutta D, Stephans JC, Shak S, Kiefer MC, Esteban JM, Baker JB (2004) Measurement of gene expression in archival paraffin-embedded tissues: development and performance of a 92-gene reverse transcriptase-polymerase chain reaction assay. Am J Pathol 164(1):35–42

    PubMed  CAS  Google Scholar 

  17. Chang JC, Wooten EC, Tsimelzon A, Hilsenbeck SG, Gutierrez MC, Tham YL, Kalidas M, Elledge R, Mohsin S, Osborne CK et al (2005) Patterns of resistance and incomplete response to docetaxel by gene expression profiling in breast cancer patients. J Clin Oncol 23(6):1169–1177

    Article  PubMed  CAS  Google Scholar 

  18. Paik S, Bryant J, Tan-Chiu E, Romond E, Hiller W, Park K, Brown A, Yothers G, Anderson S, Smith R et al (2002) Real-world performance of HER2 testing—national surgical adjuvant breast and bowel project experience. J Natl Cancer Inst 94(11):852–854

    PubMed  Google Scholar 

Download references

Acknowledgements

This study is supported in part by the Breast Cancer SPORE P50 CA50183 and R01 CA112305-01A1 from the National Cancer Institute, US Department of the Army # W81XWH-04-1-0468, the Breast Cancer Research Foundation, and the Emma Jacobs Clinical Breast Cancer Fund.

Author information

Authors and Affiliations

  1. Breast Center and the Departments of Medicine, Pathology, and Molecular and Cellular Biology, Baylor College of Medicine and the Methodist Hospital, 1 Baylor Plaza, MS 600, Houston, TX, 77030, USA

    Jenny C. Chang, M. Carolina Gutierrez, Susan G. Hilsenbeck, Krsytal Sexton, Syed Mohsin, Tara Gray, Laura Alvarez, Gary C. Chamness & C. Kent Osborne

  2. Mount Vernon Hospital, Northwood, UK

    Andreas Makris

  3. Genomic Health Inc., Redwood, CA, USA

    James R. Hackett, Jennie Jeong, Mei-Lan Liu, Joffre Baker, Kim Clark-Langone, Frederick L. Baehner & Steven Shak

Authors
  1. Jenny C. Chang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Andreas Makris
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. M. Carolina Gutierrez
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Susan G. Hilsenbeck
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. James R. Hackett
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Jennie Jeong
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Mei-Lan Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Joffre Baker
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Kim Clark-Langone
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Frederick L. Baehner
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Krsytal Sexton
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Syed Mohsin
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Tara Gray
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Laura Alvarez
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. Gary C. Chamness
    View author publications

    You can also search for this author in PubMed Google Scholar

  16. C. Kent Osborne
    View author publications

    You can also search for this author in PubMed Google Scholar

  17. Steven Shak
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Jenny C. Chang.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Chang, J.C., Makris, A., Gutierrez, M.C. et al. Gene expression patterns in formalin-fixed, paraffin-embedded core biopsies predict docetaxel chemosensitivity in breast cancer patients. Breast Cancer Res Treat 108, 233–240 (2008). https://doi.org/10.1007/s10549-007-9590-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10549-007-9590-z

Keywords

Search

Navigation