Abstract LB-296: Tumor tissue microRNA expression in association with triple negative breast cancer recurrence and mortality

Abstract

Abstract Background Triple-negative breast cancer (TNBC) accounts for 15-20% of breast cancers in the United States1. Compared with other breast cancer patients, TNBC displays high rates of metastasis, has poorer prognosis, and has no targeted therapies. microRNAs are small non-coding RNAs that function in transcriptional and post-transcriptional regulation of gene expression. Recent studies, primarily based on cell-line and animal studies, suggest that miRNA expression may be related to cancer metastasis and prognosis1-5. Purpose To systematically investigate associations of tumor expression of 38 miRNAs that have been previously implicated in breast cancer prognosis with TNBC recurrence and cancer-specific mortality. Method Included in the study were 456 TNBC cases recruited by the Shanghai Breast Cancer Survival Study between March 2002 and April 2006 and aged 20 to 75 years at diagnosis. Information on breast cancer diagnosis, treatment, demographics, lifestyle factors, and disease progression was collected approximately 6 months after diagnosis and reassessed at 18, 36, and 60 months after diagnosis in follow-up interviews. Information on disease recurrence and mortality was collected via in-person follow-up surveys and linkages with population-based cancer registry and vital statistics databases. miRNA expression levels in formalin-fixed, paraffin-embedded breast cancer tissue sections were measured using the NanoString nCounter assay. The association of miRNA expression with breast cancer recurrence and mortality was evaluated by Cox regression analysis with adjustment for age at diagnosis and TNM stage (I-IV). Results Of the 38 miRNAs evaluated, expression levels of miR-374b (P=0.0022), miR-148a (P=0.0029), miR-126 (P=0.0059), and miR-218 (P=0.0087) were significantly and inversely associated with recurrence and breast cancer mortality among TNBC patients independent of age and TNM stage. The directions of association were consistent with those previously reported in the literature. A composite score derived from the expression levels of these four miRNAs was more significantly associated with breast cancer recurrence and mortality (P=0.0001), with hazard ratios (95% confidence interval) of 1.2 (0.77-2.0), 0.53 (0.30-0.94), and 0.23 (0.11-0.48) for the second to fourth quartiles compared with the lowest quartile of scores. Conclusion In this, the largest study to date of tumor miRNA expression and TNBC outcomes, we found that miR-374b, miR-148a, miR-126, and miR-218, were individually and jointly associated with TNBC prognosis. 1. Cascione L, Gasparini P, Lovat F et al., Integrated MicroRNA and mRNA Signatures Associated with Survival in Triple Negative Breast Cancer. PLoS ONE 2013 8(2): e55910 2. Voliniaa S, Galassoa M, Sanaa M, et al., Breast cancer signatures for invasiveness and prognosis defined by deep sequencing of microRNA, PNAS 2012 109, 3024-3029 3. Png K, Halberg N, Yoshida M et al. A microRNA regulon that mediates endothelial recruitment and metastasis by cancer cells, Nature 2012 481:190-194 4. Zhang Y, Yang P, Sun T et al., miR-126 and miR-126* repress recruitment of mesenchymal stem cells and inflammatory monocytes to inhibit breast cancer metastasis. Nature Cell Biology 2013 15, 284-294 5. Pencheva N & Tavazoie S Control of metastatic progression by microRNA regulatory networks. Nature Cell Biology 2013 15, 546-554 Citation Format: Yan Liu, Qiuyin Cai, Fei Ye, Ying Zheng, Jie Wu, Yinghao Su, Hui Cai, Ping-Ping Bao, Wei Zheng, Wei Lu, Xiao-Ou Shu. Tumor tissue microRNA expression in association with triple negative breast cancer recurrence and mortality. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr LB-296. doi:10.1158/1538-7445.AM2014-LB-296