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Breast Cancer Research and Treatment

, Volume 127, Issue 1, pp 179–193 | Cite as

Prognostic utility of β-tubulin isotype III and correlations with other molecular and clinicopathological variables in patients with early breast cancer: a translational Hellenic Cooperative Oncology Group (HeCOG) study

  • George Pentheroudakis
  • Anna Batistatou
  • Konstantine T. Kalogeras
  • Ralf Kronenwett
  • Ralph M. Wirtz
  • Evangelos Bournakis
  • Anastasia G. Eleftheraki
  • Dimitrios Pectasides
  • Mattheos Bobos
  • Irini Papaspirou
  • Sevasti Kamina
  • Helen Gogas
  • Angelos K. Koutras
  • Nicholas Pavlidis
  • George Fountzilas
Clinical trial

Abstract

We evaluated the prognostic and predictive utility of β-tubulin isotype III (TUBB3) tumour gene transcription in early breast cancer patients enrolled in a randomised study. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was applied for assessment of TUBB3, ER, PgR, HER2 and MAPT messenger RNA and immunohistochemistry (IHC) for protein expression in 314 patients enrolled in trial HE10/97, evaluating epirubicin–alkylator adjuvant chemotherapy with or without paclitaxel. High TUBB3 mRNA status was associated with advanced T stage, high histological grade, low mRNA and protein levels of ER, PgR and MAPT, and high levels of HER2 (p < 0.001). At a median follow-up of 98 months, multivariate analysis showed high TUBB3 mRNA status to have prognostic significance for DFS (HR = 1.83, 95% CI 1.25–2.68, p = 0.002) and OS (HR = 1.71, 95% CI 1.03–2.83, p = 0.038), along with the number of involved axillary nodes, PgR mRNA status and tumour grade. TUBB3 mRNA levels did not predict benefit from inclusion of paclitaxel in adjuvant chemotherapy (test for interaction p = 0.96 for OS, p = 0.46 for DFS). Transcriptional activity of β-tubulin isotype III in early breast cancer is an adverse prognostic factor, though not a predictive one for taxane efficacy.

Keywords

Breast cancer β-tubulin isotype III Adjuvant chemotherapy Prognostic/predictive factors 

Notes

Acknowledgments

The authors wish to thank Ms. Evita Fragou and Ms. Dimitra Katsala for monitoring the study, Ms. Maria Moschoni for coordinating the data management and Ms. Thalia Spinari for tissue sample collection.

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Copyright information

© Springer Science+Business Media, LLC. 2011

Authors and Affiliations

  • George Pentheroudakis
    • 1
  • Anna Batistatou
    • 2
  • Konstantine T. Kalogeras
    • 3
    • 4
  • Ralf Kronenwett
    • 5
    • 13
  • Ralph M. Wirtz
    • 5
    • 14
  • Evangelos Bournakis
    • 6
  • Anastasia G. Eleftheraki
    • 7
  • Dimitrios Pectasides
    • 8
  • Mattheos Bobos
    • 9
  • Irini Papaspirou
    • 10
  • Sevasti Kamina
    • 2
  • Helen Gogas
    • 11
  • Angelos K. Koutras
    • 12
  • Nicholas Pavlidis
    • 1
  • George Fountzilas
    • 3
  1. 1.Department of Medical OncologyIoannina University HospitalIoanninaGreece
  2. 2.Department of PathologyIoannina University HospitalIoanninaGreece
  3. 3.Department of Medical OncologyPapageorgiou Hospital, Aristotle University of Thessaloniki School of MedicineThessalonikiGreece
  4. 4.Translational Research SectionHellenic Cooperative Oncology Group, Data OfficeAthensGreece
  5. 5.Siemens Healthcare DiagnosticsCologneGermany
  6. 6.Department of Clinical TherapeuticsAlexandra Hospital, University of Athens School of MedicineAthensGreece
  7. 7.Section of BiostatisticsHellenic Cooperative Oncology Group, Data OfficeAthensGreece
  8. 8.Section of Oncology, 2nd Department of Internal MedicineHippokration Hospital, University of Athens School of MedicineAthensGreece
  9. 9.Laboratory of Molecular Oncology, Hellenic Foundation for Cancer ResearchAristotle University of Thessaloniki School of MedicineThessalonikiGreece
  10. 10.Department of HistopathologyAlexandra HospitalAthensGreece
  11. 11.1st Department of MedicineLaiko General Hospital, University of Athens School of MedicineAthensGreece
  12. 12.Division of Oncology, Department of MedicineUniversity Hospital, University of Patras Medical SchoolPatrasGreece
  13. 13.Sividon Diagnostics GmbHCologneGermany
  14. 14.Stratifyer Molecular Pathology GmbHCologneGermany

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