Breast Cancer Research and Treatment

, Volume 108, Issue 2, pp 183–190

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

  • Fabrice Andre
  • Chafika Mazouni
  • Cornelia Liedtke
  • Shu-Wan Kau
  • Debby Frye
  • Marjorie Green
  • Ana M. Gonzalez-Angulo
  • W. Fraser Symmans
  • Gabriel N. Hortobagyi
  • Lajos Pusztai
Preclinical Study

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 (< 0.001). The 5-year relapse-free survival rates were 94% and 70% in HER2+ tumors with and without pCR (= 0.009). HER2 overexpression (odds ratio 2.3, 95%CI: 1.3–3.9, = 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.

Keywords

Breast neoplasms Chemotherapy Predictive biomarker HER2 Estrogen receptor Tau Topoisomerase 2α Paclitaxel Anthracycline 

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Copyright information

© Springer Science+Business Media, LLC 2007

Authors and Affiliations

  • Fabrice Andre
    • 1
    • 2
  • Chafika Mazouni
    • 2
  • Cornelia Liedtke
    • 2
  • Shu-Wan Kau
    • 2
  • Debby Frye
    • 2
  • Marjorie Green
    • 2
  • Ana M. Gonzalez-Angulo
    • 2
  • W. Fraser Symmans
    • 3
  • Gabriel N. Hortobagyi
    • 2
  • Lajos Pusztai
    • 2
  1. 1.Breast Cancer Unit and Translational Research Unit UPRES03535Institut Gustave RoussyVillejuifFrance
  2. 2.Department of Breast Medical Oncology, Unit 1354The University of Texas M. D. Anderson Cancer CenterHoustonUSA
  3. 3.Department of PathologyThe University of Texas M. D. Anderson Cancer CenterHoustonUSA

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