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 (1) , Anna Batistatou (2) , Konstantine T. Kalogeras (3, 4) , Ralf Kronenwett (5, 6) , Ralph M. Wirtz (5, 7) , Evangelos Bournakis (8) , Anastasia G. Eleftheraki (9) , Dimitrios Pectasides (10) , Mattheos Bobos (11) , Irini Papaspirou (12) , Sevasti Kamina (2) , Helen Gogas (13) , Angelos K. Koutras (14) , Nicholas Pavlidis (1) , George Fountzilas (3)

1 Department of Medical Oncology
2 Department of Pathology
3 Department of Medical Oncology
4 Translational Research Section
5 Siemens Healthcare Diagnostics
6 Sividon Diagnostics GmbH
7 Stratifyer Molecular Pathology GmbH
8 Department of Clinical Therapeutics
9 Section of Biostatistics
10 Section of Oncology, 2nd Department of Internal Medicine
11 Laboratory of Molecular Oncology, Hellenic Foundation for Cancer Research
12 Department of Histopathology
13 1st Department of Medicine
14 Division of Oncology, Department of Medicine

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 ( < 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,  = 0.002) and OS (HR = 1.71, 95% CI 1.03-2.83,  = 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  = 0.96 for OS,  = 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.

Mots clés: Breast cancer; β-tubulin isotype III; Adjuvant chemotherapy; Prognostic/predictive factors

George Pentheroudakis, Anna Batistatou, Konstantine T. Kalogeras, Ralf Kronenwett, Ralph M. Wirtz, et al.. 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. Breast Cancer Research and Treatment, 2011, 127 (1), pp.179-193. ⟨10.1007/s10549-011-1427-0⟩. ⟨hal-00620889⟩