Skip to main content

Advertisement

SpringerLink
Log in

Tau expression and efficacy of paclitaxel treatment in metastatic breast cancer

  • Original Article
  • Published:
Cancer Chemotherapy and Pharmacology Aims and scope Submit manuscript

Abstract

Purpose

Paclitaxel is widely used for the treatment of patients with metastatic breast cancer (MBC). Although several mechanisms of paclitaxel resistance have been demonstrated, useful markers of paclitaxel resistance have not been available in clinical practice.

Methods

In this study, the clinical significance of tau expression in MBC cases was established by identifying candidates with paclitaxel administration. Tissue specimens obtained from 35 patients were examined. Status of tau expression was determined by immunohistochemistry.

Results

Fifteen cases were classified as tau-negative and 20 cases were classified as tau-positive, respectively. Sixty percent of tau-negative expression showed favorable response. Conversely, 85% of tau-positive expression showed progressive or stable disease after paclitaxel administration. Time to disease progression in tau-negative and tau-positive groups was 9.4 ± 6.6 and 6.0 ± 3.7 months, respectively.

Conclusions

Patients with tau-positive expression may derive less benefit than tau-negative from paclitaxel therapy in MBC.

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

Similar content being viewed by others

References

  1. Reichman BS, Seidman AD, Crown JP, Heelan R, Hakes TB, Lebwohl DE, Gilewski TA, Surbone A, Currie V, Hudis CA et al (1993) Paclitaxel and recombinant human granulocyte colony-stimulating factor as initial chemotherapy for metastatic breast cancer. J Clin Oncol 11:1943–1951

    PubMed  CAS  Google Scholar 

  2. Seidman AD, Tiersten A, Hudis C, Gollub M, Barrett S, Yao TJ, Lepore J, Gilewski T, Currie V, Crown J et al (1995) Phase II trial of paclitaxel by 3-hour infusion as initial and salvage chemotherapy for metastatic breast cancer. J Clin Oncol 13:2575–2581

    PubMed  CAS  Google Scholar 

  3. Nabholtz JM, Gelmon K, Bontenbal M, Spielmann M, Catimel G, Conte P, Klaassen U, Namer M, Bonneterre J, Fumoleau P, Winograd B (1996) Multicenter, randomized comparative study of two doses of paclitaxel in patients with metastatic breast cancer. J Clin Oncol 14:1858–1867

    PubMed  CAS  Google Scholar 

  4. Paridaens R, Biganzoli L, Bruning P, Klijn JG, Gamucci T, Houston S, Coleman R, Schachter J, Van Vreckem A, Sylvester R, Awada A, Wildiers J, Piccart M (2000) Paclitaxel versus doxorubicin as first-line single-agent chemotherapy for metastatic breast cancer: a European Organization for Research and Treatment of Cancer Randomized Study with cross-over. J Clin Oncol 18:724–733

    PubMed  CAS  Google Scholar 

  5. Sledge GW, Neuberg D, Bernardo P, Ingle JN, Martino S, Rowinsky EK, Wood WC (2003) Phase III trial of doxorubicin, paclitaxel, and the combination of doxorubicin and paclitaxel as front-line chemotherapy for metastatic breast cancer: an intergroup trial (E1193). J Clin Oncol 21:588–592

    Article  PubMed  Google Scholar 

  6. Winer EP, Berry DA, Woolf S, Duggan D, Kornblith A, Harris LN, Michaelson RA, Kirshner JA, Fleming GF, Perry MC, Graham ML, Sharp SA, Keresztes R, Henderson IC, Hudis C, Muss H, Norton L (2004) Failure of higher-dose paclitaxel to improve outcome in patients with metastatic breast cancer: cancer and leukemia group B trial 9342. J Clin Oncol 22:2061–2068

    Article  PubMed  CAS  Google Scholar 

  7. Rowinsky EK, Donehower RC (1995) Paclitaxel. N Engl J Med 332:1004–1014

    Article  PubMed  CAS  Google Scholar 

  8. Szakács G, Paterson JK, Ludwig JA, Booth-Genthe C, Gottesman MM (2006) Targeting multidrug resistance in cancer. Nat Rev Drug Discov 5:219–234

    Article  PubMed  Google Scholar 

  9. Leonard GD, Fojo T, Bates SE (2003) The role of ABC transporters in clinical practice. Oncologist 8:411–424

    Article  PubMed  CAS  Google Scholar 

  10. Horwitz SB, Cohen D, Rao S, Ringel I, Shen HJ, Yang CP (1993) Taxol: mechanisms of action and resistance. J Natl Cancer Inst Monogr (15):55–61

  11. Bollag DM, McQueney PA, Zhu J, Hensens O, Koupal L, Liesch J, Goetz M, Lazarides E, Woods CM (1995) Epothilones, a new class of microtubule-stabilizing agents with a taxol-like mechanism of action. Cancer Res 55:2325–2333

    PubMed  CAS  Google Scholar 

  12. Kamath K, Wilson L, Cabral F, Jordan MA (2005) BetaIII-tubulin induces paclitaxel resistance in association with reduced effects on microtubule dynamic instability. J Biol Chem 280:12902–12907

    Article  PubMed  CAS  Google Scholar 

  13. Tommasi S, Mangia A, Lacalamita R, Bellizzi A, Fedele V, Chiriatti A, Thomssen C, Kendzierski N, Latorre A, Lorusso V, Schittulli F, Zito F, Kavallaris M, Paradiso A (2007) Cytoskeleton and paclitaxel sensitivity in breast cancer: the role of beta-tubulins. Int J Cancer 120:2078–2085

    Article  PubMed  CAS  Google Scholar 

  14. Paradiso A, Mangia A, Chiriatti A, Tommasi S, Zito A, Latorre A, Schittulli F, Lorusso V (2005) Biomarkers predictive for clinical efficacy of taxol-based chemotherapy in advanced breast cancer. Ann Oncol 16(Suppl 4):iv14–iv19

    Article  PubMed  Google Scholar 

  15. Basu A, DuBois G, Haldar S (2006) Posttranslational modifications of Bcl2 family members–a potential therapeutic target for human malignancy. Front Biosci 11:1508–1521

    Article  PubMed  CAS  Google Scholar 

  16. Haldar S, Basu A, Croce CM (1998) Serine-70 is one of the critical sites for drug-induced Bcl2 phosphorylation in cancer cells. Cancer Res 58:1609–1615

    PubMed  CAS  Google Scholar 

  17. Bhalla KN (2003) Microtubule-targeted anticancer agents and apoptosis. Oncogene 22:9075–9086

    Article  PubMed  CAS  Google Scholar 

  18. Shitashige M, Toi M, Yano T, Shibata M, Matsuo Y, Shibasaki F (2001) Dissociation of Bax from a Bcl-2/Bax heterodimer triggered by phosphorylation of serine 70 of Bcl-2. J Biochem 130:741–748

    PubMed  CAS  Google Scholar 

  19. Rouzier R, Rajan R, Wagner P, Hess KR, Gold DL, Stec J, Ayers M, Ross JS, Zhang P, Buchholz TA, Kuerer H, Green M, Arun B, Hortobagyi GN, Symmans WF, Pusztai L (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 

  20. Goldhirsch A, Wood WC, Gelber RD, Coates AS, Thürlimann B, Senn HJ, 10th St Gallen Conference (2007) Progress and promise: highlights of the international expert consensus on the primary therapy of early breast cancer 2007. Ann Oncol 18:1133–1144

    Article  PubMed  CAS  Google Scholar 

  21. Lu CD, Altiere DC, Tanigawa N (1998) Expression of a novel antiapoptosis gene, survivin, correlated with cell apoptosis and p53 accumulation in gastric carcinomas. Cancer Res 58:1808–1812

    PubMed  CAS  Google Scholar 

  22. Kawasaki H, Altieri DC, Lu CD, Toyoda M, Tenjo T, Tanigawa N (1998) Inhibition of apoptosis by survivin predict shorter survival rates in colorectal cancer. Cancer Res 58:5071–5074

    PubMed  CAS  Google Scholar 

  23. Tanaka K, Iwamoto S, Gon G, Nohara T, Iwamoto M, Tanigawa N (2000) Expression of survivin and its relationship to loss of apoptosis in breast cancer. Clin Cancer Res 6:127–134

    PubMed  CAS  Google Scholar 

  24. Ellis MJ, Hayes DF, Lippman ME (2000) Treatment of metastatic breast cancer. In: Harris JR, Lippman ME, Morrow M, Osborne CK (eds) Diseases of the breast, 2nd edn. Lippincott, Williams and Wilkins, Philadelphia, pp 749–797

    Google Scholar 

  25. West M, Blanchette C, Dressman H, Huang E, Ishida S, Spang R, Zuzan H, Olson JA Jr, Marks JR, Nevins JR (2001) Predicting the clinical status of human breast cancer by using gene expression profiles. Proc Natl Acad Sci USA 98:11462–11467

    Article  PubMed  CAS  Google Scholar 

  26. Matsuno A, Takekoshi S, Sanno N, Utsunomiya H, Ohsugi Y, Saito N, Kanemitsu H, Tamura A, Nagashima T, Osamura RY, Watanabe K (1997) 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 45:805–813

    PubMed  CAS  Google Scholar 

  27. Ferreira A, Caceres A (1991) Estrogen-enhanced neurite growth: evidence for a selective induction of Tau and stable microtubules. J Neurosci 11:392–400

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of General and Gastroenterological Surgery, Osaka Medical College, 2-7 Daigaku-machi, Takatsuki City, Osaka, 569-8686, Japan

    Satoru Tanaka, Takehiro Nohara, Mitsuhiko Iwamoto, Kazuhiro Sumiyoshi, Kousei Kimura, Yuko Takahashi & Nobuhiko Tanigawa

Authors
  1. Satoru Tanaka
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Takehiro Nohara
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Mitsuhiko Iwamoto
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Kazuhiro Sumiyoshi
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Kousei Kimura
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Yuko Takahashi
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Nobuhiko Tanigawa
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Nobuhiko Tanigawa.

Additional information

No financial support was received for this study.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Tanaka, S., Nohara, T., Iwamoto, M. et al. Tau expression and efficacy of paclitaxel treatment in metastatic breast cancer. Cancer Chemother Pharmacol 64, 341–346 (2009). https://doi.org/10.1007/s00280-008-0877-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00280-008-0877-5

Keywords

Search

Navigation