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.
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.
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.
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
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.