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Poster display session

3161 - Low expression of miR-20a-5p predicts benefit to bevacizumab in metastatic breast cancer patients treated within the TANIA trial

Date

11 Sep 2017

Session

Poster display session

Presenters

Simon Peter Gampenrieder

Citation

Annals of Oncology (2017) 28 (suppl_5): v22-v42. 10.1093/annonc/mdx363

Authors

S.P.P. Gampenrieder1, G. Rinnerthaler1, H. Hackl2, M. Steiner1, C. Monzo Fuentes1, C. Hufnagl3, C. Hauser-Kronberger3, A. Egle1, R. Greil1

Author affiliations

  • 1 Iiird Medical Department With Hematology, Medical Oncology, Hemostaseology, Infectious Diseases And Rheumatology, Oncologic Center; Salzburg Cancer Research Institute (scri) With Laboratory Of Immunological And Molecular Cancer Research (limcr) And Center, Paracelsus Medical University Salzburg, 502050 - Salzburg/AT
  • 2 Division Of Bioinformatics, Biocenter, Medical University of Innsbruck, 6020 - Innsbruck/AT
  • 3 Department Of Pathology, Paracelsus Medical University Salzburg, 502050 - Salzburg/AT
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Resources

Abstract 3161

Background

Biomarkers predicting response to a bevacizumab containing therapy in metastatic breast cancer (MBC) are of urgent need. MicroRNAs (miRNAs) are involved in regulation of angiogenesis and development of treatment resistance and could therefore provide predictive information.

Methods

Profiling of 754 miRNAs was performed in FFPE tumor samples from 58 MBC patients who received bevacizumab-containing first-line treatment (learning set). Based on median PFS patients were divided into responders (R) and non-responders (NR). Differentially expressed miRNAs between R and NR were selected and validated in a cohort of 57 patients treated with first-line chemotherapy without bevacizumab (control set), to exclude miRNAs providing prognostic information only. In the learning set a multivariate analysis including clinical and pathological information was performed. MiRNAs significantly associated with PFS were further validated in 203 patients treated within the TANIA phase III trial randomizing between chemotherapy plus bevacizumab and chemotherapy alone for two consecutive treatment lines in patients pretreated with bevacizumab in first-line.

Results

Low expression of five miRNAs (miR-9-5p, miR-20a-5p, miR-21-5p, miR-210-3p, and miR-224-5p) was significantly associated with longer PFS in the learning set. For miR-20a-5p (P = 0.035) and miR-21-5p (P = 0.004) this association remained significant in multivariate analysis. In the control set no correlation between expression of those five miRNAs and PFS was seen. In tumor samples from the TANIA trial, low expression of miR-20a-5p was also significantly associated with longer second-line PFS and longer OS in the bevacizumab arm (HR 0.60, 95%CI 0.37-0.89; P = 0.012 and HR 0.54; 95%CI 0.32-0.83; P = 0.007, respectively) but not in the chemotherapy only arm (HR 0.73, 95%CI 0.48-1.09; P = 0.119 and HR 1.01 95%CI 0.63-1.62; P = 0.964, respectively). For miR-21-5p no significant association with PFS or OS in both treatment arms was observed.

Conclusions

MiR-20a-5p expression in breast cancer tissue showed a promising predictive value for identifying patients deriving greater benefit from bevacizumab-containing therapy.

Clinical trial identification

Legal entity responsible for the study

Richard Greil for the translational research project, Roche for the TANIA trial

Funding

Roche

Disclosure

S.P.P. Gampenrieder, G. Rinnerthaler, A. Egle, R. Greil: Advisory role, speakers’ honoraria, travel grants, research funding (no personal payment) from Roche. C. Monzo Fuentes: Travel grants from Roche. C. Hufnagl, C. Hauser-Kronberger: Travel grants, research funding (no personal payment) from Roche. All other authors have declared no conflicts of interest.

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