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Tau expression correlated with breast cancer sensitivity to taxanes-based neoadjuvant chemotherapy

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Tumor Biology

Abstract

The purpose of this study was to investigate the correlation between tau expression in primary breast cancer and sensitivity to taxanes during neoadjuvant chemotherapy in patients with breast cancer. We used immunohistochemistry to examine tau expression in breast cancer biopsies from 113 primary breast cancer patients and evaluated the correlation between tau expression and taxane sensitivity. Twenty-eight (24.78 %, 28/113) patients were positive for tau expression. After taxanes-based neoadjuvant chemotherapy, 40 patients achieved pathological complete response (pCR) (35.4 %). Among the 40 patients with pCR, five (12.5 %) were positive for tau expression. In univariate analysis, estrogen receptor (ER), progesterone receptor, human epidermal growth factor receptor 2 (HER2), and tau were found to be significantly predictive of a pCR (P = 0.001, 0.030, 0.002, and 0.025, respectively). Tau, ER, and HER2 status were significant for pCR on multivariate analysis (P = 0.025, 0.005, and 0.043, respectively). Tau expression was positively related to ER (P = 0.007) and progestin receptor (P = 0.008). In conclusion, tau protein expression correlated with breast cancer sensitivity to taxanes-based neoadjuvant chemotherapy; patients negative for tau expression were more likely to achieve pCR.

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References

  1. Kuerer HM, Newman LA, Smith TL, Ames FC, Hunt KK, Dhingra K, et al. Clinical course of breast cancer patients with complete pathologic primary tumor and axillary lymph node response to doxorubicin-based neoadjuvant chemotherapy. J Clin Oncol. 1999;17:460–9.

    PubMed  CAS  Google Scholar 

  2. Papademetriou K, Ardavanis A, Kountourakis P. Neoadjuvant therapy for locally advanced breast cancer: focus on chemotherapy and biological targeted treatments’ armamentarium. J Thorac Dis. 2010;2:160–70.

    PubMed  CAS  Google Scholar 

  3. Zhou X, Liu Q. Clinicopathological characters of triple negative breast cancer. Chin J Cancer Res. 2010;22:17–20.

    Article  Google Scholar 

  4. Wedam SB, Yang SX. Neoadjuvant bevacizumab and chemotherapy in breast cancer. Transl Cancer Res. 2012;1:57–8.

    Google Scholar 

  5. Henderson IC, Berry DA, Demetri GD, Cirrincione CT, Goldstein LJ, Martino S, et al. Improved outcomes from adding sequential paclitaxel but not from escalating doxorubicin dose in an adjuvant chemotherapy regimen for patients with node-positive primary breast cancer. J Clin Oncol. 2003;21:976–83.

    Article  PubMed  CAS  Google Scholar 

  6. Mamounas EP, Bryant J, Lembersky B, Fehrenbacher L, Sedlacek SM, Fisher B, et al. Paclitaxel after doxorubicin plus cyclophosphamide as adjuvant chemotherapy for node-positive breast cancer: results from NSABP B-28. J Clin Oncol. 2005;23:3686–96.

    Article  PubMed  CAS  Google Scholar 

  7. Hayes DF, Thor AD, Dressler LG, Weaver D, Edgerton S, Cowan D, et al. HER2 and response to paclitaxel in node-positive breast cancer. N Engl J Med. 2007;357:1496–506.

    Article  PubMed  CAS  Google Scholar 

  8. Murray S, Briasoulis E, Linardou H, Bafaloukos D, Papadimitriou C. Taxane resistance in breast cancer: mechanisms, predictive biomarkers and circumvention strategies. Cancer Treat Rev. 2012;38:890–903.

    Article  PubMed  CAS  Google Scholar 

  9. Rouzier R, Rajan R, Wagner P, Hess KR, Gold DL, Stec J, et al. Microtubule-associated protein tau: a marker of paclitaxel sensitivity in breast cancer. Proc Natl Acad Sci U S A. 2005;102:8315–20.

    Article  PubMed  CAS  Google Scholar 

  10. Rody A, Karn T, Gätje R, Ahr A, Solbach C, Kourtis K, et al. Gene expression profiling of breast cancer patients treated with docetaxel, doxorubicin, and cyclophosphamide within the GEPARTRIO trial: HER-2, but not topoisomerase II alpha and microtubule-associated protein tau, is highly predictive of tumor response. Breast. 2007;16:86–93.

    Article  PubMed  CAS  Google Scholar 

  11. Baquero MT, Lostritto K, Gustavson MD, Bassi KA, Appia F, Camp RL, et al. Evaluation of prognostic and predictive value of microtubule associated protein tau in two independent cohorts. Breast Cancer Res. 2011;13:R85.

    Article  PubMed  CAS  Google Scholar 

  12. Mazouni C, Peintinger F, Wan-Kau S, Andre F, Gonzalez-Angulo AM, Symmans WF, et al. Residual ductal carcinoma in situ in patients with complete eradication of invasive breast cancer after neoadjuvant chemotherapy does not adversely affect patient outcome. J Clin Oncol. 2007;25:2650–5.

    Article  PubMed  CAS  Google Scholar 

  13. Andreadis A, Brown WM, Kosik KS. Structure and novel exons of the human tau gene. Biochemistry. 1992;31:10626–33.

    Article  PubMed  CAS  Google Scholar 

  14. Kar S, Fan J, Smith MJ, Goedert M, Amos LA. Repeat motifs of tau bind to the insides of microtubules in the absence of taxol. EMBO J. 2003;22:70–7.

    Article  PubMed  CAS  Google Scholar 

  15. Wagner P, Wang B, Clark E, Lee H, Rouzier R, Pusztai L. Microtubule associated protein (MAP)-tau: a novel mediator of paclitaxel sensitivity in vitro and in vivo. Cell Cycle. 2005;4:1149–52.

    Article  PubMed  CAS  Google Scholar 

  16. Ikeda H, Taira N, Hara F, Fujita T, Yamamoto H, Soh J, et al. The estrogen receptor influences microtubule-associated protein tau (MAPT) expression and the selective estrogen receptor inhibitor fulvestrant downregulates MAPT and increases the sensitivity to taxane in breast cancer cells. Breast Cancer Res. 2010;12:R43.

    Article  PubMed  Google Scholar 

  17. Andre F, Hatzis C, Anderson K, Sotiriou C, Mazouni C, Mejia J, et al. Microtubule-associated protein-tau is a bifunctional predictor of endocrine sensitivity and chemotherapy resistance in estrogen receptor-positive breast cancer. Clin Cancer Res. 2007;13:2061–7.

    Article  PubMed  CAS  Google Scholar 

  18. Pentheroudakis G, Kalogeras KT, Wirtz RM, Grimani I, Zografos G, Gogas H, et al. Gene expression of estrogen receptor, progesterone receptor and microtubule-associated protein Tau in high-risk early breast cancer: a quest for molecular predictors of treatment benefit in the context of a Hellenic Cooperative Oncology Group trial. Breast Cancer Res Treat. 2009;116:131–43.

    Article  PubMed  CAS  Google Scholar 

  19. Pusztai L, Jeong JH, Gong Y, Ross JS, Kim C, Paik S, et al. Evaluation of microtubule-associated protein-Tau expression as a prognostic and predictive marker in the NSABP-B 28 randomized clinical trial. J Clin Oncol. 2009;27:4287–92.

    Article  PubMed  CAS  Google Scholar 

  20. Andre F, Mazouni C, Liedtke C, Kau SW, Frye D, Green M, et al. HER2 expression and efficacy of preoperative paclitaxel/FAC chemotherapy in breast cancer. Breast Cancer Res Treat. 2008;108:183–90.

    Article  PubMed  CAS  Google Scholar 

  21. Hess KR, Anderson K, Symmans WF, Valero V, Ibrahim N, Mejia JA, et al. Pharmacogenomic predictor of sensitivity to preoperative chemotherapy with paclitaxel and fluorouracil, doxorubicin, and cyclophosphamide in breast cancer. J Clin Oncol. 2006;24:4236–44.

    Article  PubMed  CAS  Google Scholar 

  22. Peintinger F, Anderson K, Mazouni C, Kuerer HM, Hatzis C, Lin F, et al. Thirty-gene pharmacogenomic test correlates with residual cancer burden after preoperative chemotherapy for breast cancer. Clin Cancer Res. 2007;13:4078–82.

    Article  PubMed  CAS  Google Scholar 

  23. Dumontet C, Krajewska M, Treilleux I, Mackey JR, Martin M, Rupin M, et al. BCIRG 001 molecular analysis: prognostic factors in node-positive breast cancer patients receiving adjuvant chemotherapy. Clin Cancer Res. 2010;16:3988–97.

    Article  PubMed  CAS  Google Scholar 

  24. Tewari M, Krishnamurthy A, Shukla HS. Predictive markers of response to neoadjuvant chemotherapy in breast cancer. Surg Oncol. 2008;17:301–11.

    Article  PubMed  Google Scholar 

  25. Chirgwin J. Do the results of BIG 1-98 assist with patient management decisions? Transl Cancer Res. 2012;1:113–6.

    Google Scholar 

  26. Wheeler SB, Reeder-Hayes K, Meyer AM. A balancing act for breast cancer? Everolimus for hormone receptor positive patients. Transl Cancer Res. 2012;1:109–12.

    Google Scholar 

  27. Ring AE, Smith IE, Ashley S, Fulford LG, Lakhani SR. Oestrogen receptor status, pathological complete response and prognosis in patients receiving neoadjuvant chemotherapy for early breast cancer. Br J Cancer. 2004;91:2012–7.

    Article  PubMed  CAS  Google Scholar 

  28. Sánchez-Muñoz A, García-Tapiador AM, Martínez-Ortega E, Dueñas-García R, Jaén-Morago A, Ortega-Granados AL, et al. Tumour molecular subtyping according to hormone receptors and HER2 status defines different pathological complete response to neoadjuvant chemotherapy in patients with locally advanced breast cancer. Clin Transl Oncol. 2008;10:646–53.

    Article  PubMed  Google Scholar 

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Acknowledgments

This study was supported by Science and Technology Planning Project of Guangdong Province, China (2008B030301356), and Guangdong Provincial Key Technology Research (2005B30301009).

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Authors and Affiliations

  1. Department of Breast Cancer, Cancer Center, Guangdong General Hospital & Guangdong Academy of Medical Sciences, Guangzhou, 510080, China

    Kun Wang, Quan-Tong Deng, Ning Liao, Guo-Chun Zhang, Jian Zu & Xue-Rui Li

  2. Department of Pathology and Laboratory Medicine, Guangdong General Hospital & Guangdong Academy of Medical Sciences, Guangzhou, 510080, China

    Yan-Hui Liu & Fang-Ping Xu

  3. Cancer Center, Guangdong General Hospital (GGH) & Guangdong Academy of Medical Sciences, Guangzhou, 510080, China

    Yi-Long Wu

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  1. Kun Wang
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  2. Quan-Tong Deng
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Correspondence to Yi-Long Wu.

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Wang, K., Deng, QT., Liao, N. et al. Tau expression correlated with breast cancer sensitivity to taxanes-based neoadjuvant chemotherapy. Tumor Biol. 34, 33–38 (2013). https://doi.org/10.1007/s13277-012-0507-z

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  • DOI: https://doi.org/10.1007/s13277-012-0507-z

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