Tumor Biology

, Volume 36, Issue 5, pp 3941–3947 | Cite as

Predictive value of microtubule-associated protein Tau in patients with recurrent and metastatic breast cancer treated with taxane-containing palliative chemotherapy

  • Jie Zhou
  • Shikun Qian
  • Hongsheng Li
  • Weixing He
  • Xiaojun Tan
  • Qiong Zhang
  • Guodong Han
  • Guiquan Chen
  • Rongcheng Luo
Research Article


Tau is a member of microtubule-associated proteins (MAPs) and expressed in normal breast epithelium and breast cancer cells. Tau expression levels in early breast cancer were correlated with the responsiveness of taxane-containing chemotherapy. However, it is unknown whether Tau contributes to breast cancer progression. Herein, Tau expression in recurrent and metastatic breast cancer (RMBC) and its predictive significance in taxane-containing palliative chemotherapy were investigated. Immunohistochemical (IHC) staining was conducted to detect Tau protein expression levels in biopsies from 285 patients with RMBC, and the correlation between Tau expression and sensitivity to taxane was evaluated. One hundred twety-one (42.46 %, 121/285) patients were Tau positive in their tumor. One hundred ninety-four (68.07 %, 194/285) patients were effective clinical remission, which evaluated with response evaluation criteria in solid tumors (RECIST) criteria. In this group, 141 (85.98 %, 141/194) patients were Tau negative. We further analyzed the correlation between Tau expression and clinicopathological characteristics. Tau expression was positively correlated to estrogen receptor (ER) status. Multivariate logistic regression analysis showed that Tau expression significantly differentiated patients with effective response to treatment (95 % confidence interval (CI): 4.230–13.88, P < 0.01). Tau expression was identified as an independent factor to predict the sensitivity of tumors to taxane-containing palliative chemotherapy in RMBC, suggesting that Tau expression in RMBC may serve as a clinical predictor for taxane-containing palliative chemotherapy.


Tau protein Recurrent and metastasis Breast cancer Taxane 



This study was supported by the Guangzhou Health Foundation of Guangdong Province, China (grant no. 20121A011166).

Conflicts of interest



  1. 1.
    Qiu J, Yang M, Chen W, Gao X, Liu S, Shi S, et al. Prevalence and correlates of major depressive disorder in breast cancer survivors in Shanghai, China. Psycho-Oncology. 2012;21:1331–7.CrossRefPubMedGoogle Scholar
  2. 2.
    Saphner T, Tormey DC, Gray R. Annual hazard rates of recurrence for breast cancer after primary therapy. J Clin Oncol. 1996;14:2738–46.CrossRefPubMedGoogle Scholar
  3. 3.
    Christiansen P, Al-Suliman N, Bjerre K, Møller S. Recurrence pattern and prognosis in low-risk breast cancer patients—data from the DBCG 89-A programme. Acta Oncol. 2008;47:691–703.CrossRefPubMedGoogle Scholar
  4. 4.
    Piccart-Gebhart MJ, Burzykowski T, Buyse M, Sledge G, Carmichael J, Lück H-J, et al. Taxanes alone or in combination with anthracyclines as first-line therapy of patients with metastatic breast cancer. J Clin Oncol. 2008;26:1980–6.CrossRefPubMedGoogle Scholar
  5. 5.
    Cuppone F, Bria E, Carlini P, Milella M, Felici A, Sperduti I, et al. Taxanes as primary chemotherapy for early breast cancer. Cancer. 2008;113:238–46.CrossRefPubMedGoogle Scholar
  6. 6.
    Mazouni C, Kau SW, Frye D, Andre F, Kuerer HM, Buchholz TA, et al. Inclusion of taxanes, particularly weekly paclitaxel, in preoperative chemotherapy improves pathologic complete response rate in estrogen receptor-positive breast cancers. Ann Oncol. 2007;18:874–80.CrossRefPubMedGoogle Scholar
  7. 7.
    McGrogan BT, Gilmartin B, Carney DN, McCann A. Taxanes, microtubules and chemoresistant breast cancer. Biochim Biophys Acta (BBA) Rev Cancer. 2008;1785:96–132.CrossRefGoogle Scholar
  8. 8.
    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.CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    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.CrossRefPubMedGoogle Scholar
  10. 10.
    Qin Y-Y, Li H, Guo X-J, Ye X-F, Wei X, Zhou Y-H, et al. Adjuvant chemotherapy, with or without taxanes, in early or operable breast cancer: a meta-analysis of 19 randomized trials with 30,698 patients. PLoS ONE. 2011;6:e26946.CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Drechsel DN, Hyman AA, Cobb MH, Kirschner MW. Modulation of the dynamic instability of tubulin assembly by the microtubule-associated protein Tau. Mol Biol Cell. 1992;3:1141–54.CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Smith CJ, Anderton BH, Davis DR, Gallo JM. Tau isoform expression and phosphorylation state during differentiation of cultured neuronal cells. FEBS Lett. 1995;375:243–8.CrossRefPubMedGoogle Scholar
  13. 13.
    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.CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Li Z-H, Xiong Q-Y, Tu J-H, Gong Y, Qiu W, Zhang H-Q, et al. Tau proteins expressions in advanced breast cancer and its significance in taxane-containing neoadjuvant chemotherapy. Med Oncol. 2013;30:1–7.Google Scholar
  15. 15.
    Wang K, Deng Q-T, Liao N, Zhang G-C, Liu Y-H, Xu F-P, et al. Tau expression correlated with breast cancer sensitivity to taxanes-based neoadjuvant chemotherapy. Tumor Biol. 2013;34:33–8.CrossRefGoogle Scholar
  16. 16.
    Goldhirsch A, Wood WC, Gelber RD, Coates AS, Thürlimann B, Senn HJ, et al. Progress and promise: highlights of the international expert consensus on the primary therapy of early breast cancer 2007. Ann Oncol. 2007;18:1133–44.CrossRefPubMedGoogle Scholar
  17. 17.
    Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, et al. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer. 2009;45:228–47.CrossRefPubMedGoogle Scholar
  18. 18.
    Ellis MJ. Mutational analysis of breast cancer: guiding personalized treatments. Breast (Edinburgh, Scotland). 2013;22:S19–21.CrossRefGoogle Scholar
  19. 19.
    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.CrossRefPubMedGoogle Scholar
  20. 20.
    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.CrossRefPubMedGoogle Scholar
  21. 21.
    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.CrossRefPubMedGoogle Scholar
  22. 22.
    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.CrossRefPubMedGoogle Scholar
  23. 23.
    Cortes J, Baselga J. Targeting the microtubules in breast cancer beyond taxanes: the epothilones. Oncologist. 2007;12:271–80.CrossRefPubMedGoogle Scholar
  24. 24.
    Noguchi S. Predictive factors for response to docetaxel in human breast cancers. Cancer Sci. 2006;97:813–20.CrossRefPubMedGoogle Scholar
  25. 25.
    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.CrossRefPubMedGoogle Scholar
  26. 26.
    Pentheroudakis G, Kalogeras K, Wirtz R, 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.CrossRefPubMedGoogle Scholar
  27. 27.
    Pusztai L, Jeong J-H, 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.CrossRefPubMedPubMedCentralGoogle Scholar
  28. 28.
    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.CrossRefPubMedGoogle Scholar
  29. 29.
    Spicakova T, O’Brien MM, Duran GE, Sweet-Cordero A, Sikic BI. Expression and silencing of microtubule-associated protein Tau in breast cancer cells. Mol Cancer Ther. 2010;9:2970–81.CrossRefPubMedPubMedCentralGoogle Scholar
  30. 30.
    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.CrossRefPubMedGoogle Scholar
  31. 31.
    Baquero MT, Hanna JA, Neumeister V, Cheng H, Molinaro AM, Harris LN, et al. Stathmin expression and its relationship to microtubule-associated protein Tau and outcome in breast cancer. Cancer. 2012;118:4660–9.CrossRefPubMedPubMedCentralGoogle Scholar
  32. 32.
    Matsuno A, Takekoshi S, Sanno N, Utsunomiya H, Ohsugi Y, Saito N, et al. Modulation of protein kinases and microtubule-associated proteins and changes in ultrastructure in female rat pituitary cells: effects of estrogen and bromocriptine. J Histochem Cytochem. 1997;45:805–13.CrossRefPubMedGoogle Scholar
  33. 33.
    Ferreira A, Caceres A. Estrogen-enhanced neurite growth: evidence for a selective induction of tau and stable microtubules. J Neurosci. 1991;11:392–400.PubMedGoogle Scholar
  34. 34.
    West M, Blanchette C, Dressman H, Huang E, Ishida S, Spang R, et al. Predicting the clinical status of human breast cancer by using gene expression profiles. Proc Natl Acad Sci. 2001;98:11462–7.CrossRefPubMedPubMedCentralGoogle Scholar
  35. 35.
    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.CrossRefPubMedPubMedCentralGoogle Scholar
  36. 36.
    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. 2008;116:131–43.CrossRefPubMedGoogle Scholar

Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2015

Authors and Affiliations

  • Jie Zhou
    • 1
    • 2
  • Shikun Qian
    • 3
  • Hongsheng Li
    • 2
  • Weixing He
    • 2
  • Xiaojun Tan
    • 4
  • Qiong Zhang
    • 4
  • Guodong Han
    • 2
  • Guiquan Chen
    • 2
  • Rongcheng Luo
    • 1
  1. 1.Cancer Center, Traditional Chinese Medicine-Integrated HospitalSouthern Medical UniversityGuangzhouChina
  2. 2.Department of Breast OncologyCancer Center of Guangzhou Medical UniversityGuangzhouChina
  3. 3.Department of Hepatobiliary SurgeryThe Second Affiliated Hospital of Guangzhou Medical UniversityGuangzhouChina
  4. 4.Department of PathologyCancer Center of Guangzhou Medical UniversityGuangzhouChina

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