Skip to main content

Advertisement

SpringerLink
Log in

HER2 expression and efficacy of preoperative paclitaxel/FAC chemotherapy in breast cancer

  • Preclinical Study
  • Published:
Breast Cancer Research and Treatment Aims and scope Submit manuscript

Abstract

Purpose

We examined the correlation between HER2 expression and pathologic complete response (pCR) to paclitaxel/FAC (T/FAC) preoperative chemotherapy in breast cancer.

Patients and Methods

Retrospective analysis of data including 534 patients treated with preoperative T/FAC was performed. Gene expression results were available from two datasets of 132 and 286 patients, and were used to examine the co-expression of HER2 and topoisomerase II α (TOP2A) and microtubule associated protein tau (MAP-Tau).

Results

Of the 534 patients, 105 (20%) had HER2-overexpressing breast cancer. The pCR rates were 33% and 15% for patients with HER2+ and HER2- tumors (P < 0.001). The 5-year relapse-free survival rates were 94% and 70% in HER2+ tumors with and without pCR (P = 0.009). HER2 overexpression (odds ratio 2.3, 95%CI: 1.3–3.9, P = 0.004), estrogen receptor (ER) status, grade and weekly schedule of paclitaxel were each significantly and independently associated with pCR in multivariate analysis. When patients were stratified by ER status, the pCR rates were 50% for HER2+/ER−, 30% for HER2−/ER−, 19% for HER2+/ER+, and 6% for HER2−/ER+ tumors. HER2 overexpression was associated with lower expression of MAP-tau (P = 0.001 and P < 0.001) and higher expression of TOP2A mRNAs (P = 0.048 and P = 0.001) in patients with ER+ disease. ER− cancers had low MAP-tau expression regardless of HER-status.

Conclusion

HER2 overexpression is associated with higher rate of pCR to preoperative T/FAC chemotherapy regardless of ER status. HER2 overexpression also correlates with increased TOP2A and decreased MAP-tau expression in ER-positive cancers.

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. Early Breast Cancer Trialists’ Collaborative Group (EBCTCG) (2005) Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomised trials. Lancet 365:1687–1717

    Article  CAS  Google Scholar 

  2. International Breast Cancer Study Group (2002) Endocrine responsiveness and tailoring adjuvant therapy for postmenopausal lymph node-negative breast cancer: a randomized trial. J Natl Cancer Inst 94:1054–1065

    Google Scholar 

  3. Albain K, Barlow W, O’Malley F et al (2004) Concurrent (CAFT) versus sequential (CAF-T) chemohormonal therapy (cyclophosphamide, doxorubicin, 5-fluorouracil, tamoxifen) versus T alone for postmenopausal , node-positive, estrogen (ER) and/or progesterone (PgR) receptor-positive breast cancer: mature outcomes and new biologic correlates on phase III intergroup trial 0100 (SWOG-8814). San Antonio Breast Cancer Symposium, Abst 37

  4. Pritchard KI, Shepherd LE, O’Malley FP et al (2006) HER2 and responsiveness of breast cancer to adjuvant chemotherapy. N Engl J Med 354:2103–2111

    Article  PubMed  CAS  Google Scholar 

  5. Hayes DF, Thor A, Dressler L et al (2006) HER2 predicts benefit from adjuvant paclitaxel after AC in node-positive breast cancer: CALGB 9344. J Clin Oncol 24:18S Abs 510

    Article  Google Scholar 

  6. Rouzier R, Pusztai L, Delaloge S et al (2005) Nomograms to predict pathologic complete response and metastasis-free survival after preoperative chemotherapy for breast cancer. J Clin Oncol 23:8331–8339

    Article  PubMed  Google Scholar 

  7. Von Minckwitz G, Raab G, Caputo A et al (2005) Doxorubicin with cyclophosphamide followed by docetaxel every 21 days compared with doxorubicin and docetaxel every 14 days as preoperative treatment in operable breast cancer: the GEPARDUO study of the German Breast Group. J Clin Oncol 23:2676–2685

    Article  CAS  Google Scholar 

  8. Colleoni M, Viale G, Zahrieh D et al (2004) Chemotherapy is more effective in patients with breast cancer not expressing steroid hormone receptors: a study of preoperative treatment. Clin Cancer Res 10:6622–6628

    Article  PubMed  CAS  Google Scholar 

  9. Gonzalez-Angulo AM, Krishnamurthy S, Yamamura Y et al (2004) Lack of association between amplification of HER2 and response to preoperative taxanes in patients with breast carcinoma. Cancer 101:258–263

    Article  PubMed  CAS  Google Scholar 

  10. Schneeweiss A, Katretchko J, Sinn HP et al (2004) Only grading has independent impact on breast cancer survival after adjustment for pathological response to preoperative chemotherapy. Anticancer Drugs 15:127–135

    Article  PubMed  CAS  Google Scholar 

  11. Learn PA, Yeh IT, McNutt M et al (2005) HER2/neu expression as a predictor of response to neoadjuvant docetaxel in patients with operable breast carcinoma. Cancer 103:2252–2260

    Article  PubMed  CAS  Google Scholar 

  12. Petit T, Wilt M, Velten M et al (2004) Comparative value of tumour grade, hormonal receptors, Ki-67, HER2 and topoisomerase II alpha status as predictive markers in breast cancer patients treated with neoadjuvant anthracycline-based chemotherapy. Eur J Cancer 40:205–211

    Article  PubMed  CAS  Google Scholar 

  13. Penault-Llorca F, Cayre A, Bouchet Mishellany F et al (2003) Induction chemotherapy for breast carcinoma: predictive markers and relation with outcome. Int J Oncol 22:1319–1325

    PubMed  CAS  Google Scholar 

  14. Zhang F, Yang Y, Smith T et al (2003) Correlation between HER2 expression and response to neoadjuvant chemotherapy with 5-fluorouracil, doxorubicin, and cyclophosphamide in patients with breast carcinoma. Cancer 97:1758–1765

    Article  PubMed  CAS  Google Scholar 

  15. Di Leo A, Isola J. (2003) Topoisomerase II alpha as a marker predicting the efficacy of anthracyclines in breast cancer: are we at the end of the beginning? Clin Breast Cancer 4:179–186

    Article  PubMed  CAS  Google Scholar 

  16. Rouzier R, Rajan R, Wagner P et al. (2005) Microtubule-associated protein tau: a marker of paclitaxel sensitivity in breast cancer. Proc Natl Acad Sci USA 102:8315–8320

    Article  PubMed  CAS  Google Scholar 

  17. Hess KR, Anderson K, Symmans W et al (2006) Pharmacogenomic predictor of sensitivity to preoperative paclitaxel and 5-fluorouracil, doxorubicin, cyclophosphamide chemotherapy in breast cancer. J Clin Oncol 24:4236–4244

    Article  PubMed  CAS  Google Scholar 

  18. Wang Y, Klijn JG, Zhang Y et al (2005) Gene-expression profiles to predict distant metastasis of lymph-node-negative primary breast cancer. Lancet 365:671–679

    PubMed  CAS  Google Scholar 

  19. Yu D, Hung MC (2000) Role of erbB2 in breast cancer chemosensitivity. Bioessays 22:673–680

    Article  PubMed  CAS  Google Scholar 

  20. Hicks DG, Yoder BJ, Pettay J et al (2005) The incidence of topoisomerase II-alpha genomic alterations in adenocarcinoma of the breast and their relationship to human epidermal growth factor receptor-2 gene amplification: a fluorescence in situ hybridization study. Hum Pathol 36:348–356

    Article  PubMed  CAS  Google Scholar 

  21. MacGrogan G, Rudolph P, Mascarel I et al (2003) DNA topoisomerase IIα expression and the response to primary chemotherapy in breast cancer. Br J Cancer 89:666–671

    Article  PubMed  CAS  Google Scholar 

  22. Park K, Kim J, Lim S et al (2003) Topoisomerase II-α (topoII) and HER2 amplification in breast cancers and response to preoperative doxorubicin chemotherapy. Eur J Cancer 39:631–634

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgements

Supported by grants to L.P. from the NCI (RO1-CA106290), the Breast Cancer Research Foundation, and the Goodwin Foundation and to G.N.H. by the Nellie B. Connally Breast Cancer Research Fund. F.A is supported by Fondation de France, Fondation Lilly and a career development award from the American Society of Clinical Oncology. C.M. is supported by Fondation de France and the Federation Nationale des Centres de lutte Contre le Cancer, Paris. C.L. is supported by the Deutsche Forschungsgemeinschaft.

Author information

Authors and Affiliations

  1. Breast Cancer Unit and Translational Research Unit UPRES03535, Institut Gustave Roussy, Villejuif, France

    Fabrice Andre

  2. Department of Breast Medical Oncology, Unit 1354, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX, 77030-1439, USA

    Fabrice Andre, Chafika Mazouni, Cornelia Liedtke, Shu-Wan Kau, Debby Frye, Marjorie Green, Ana M. Gonzalez-Angulo, Gabriel N. Hortobagyi & Lajos Pusztai

  3. Department of Pathology, The University of Texas M. D. Anderson Cancer Center, Houston, TX, USA

    W. Fraser Symmans

Authors
  1. Fabrice Andre
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Chafika Mazouni
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Cornelia Liedtke
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Shu-Wan Kau
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Debby Frye
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Marjorie Green
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Ana M. Gonzalez-Angulo
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. W. Fraser Symmans
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Gabriel N. Hortobagyi
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Lajos Pusztai
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Lajos Pusztai.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Andre, F., Mazouni, C., Liedtke, C. et al. HER2 expression and efficacy of preoperative paclitaxel/FAC chemotherapy in breast cancer. Breast Cancer Res Treat 108, 183–190 (2008). https://doi.org/10.1007/s10549-007-9594-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10549-007-9594-8

Keywords

Search

Navigation