global microrna expression profiling of high-risk er+ breast cancers from patients receiving adjuvant tamoxifen mono-therapy a dbcg study全球微表情分析患者的高危乳腺癌er +辅助它莫西芬mono-therapy dbcg研究.pdfVIP

Global MicroRNA Expression Profiling of High-Risk ER+ Breast Cancers from Patients Receiving Adjuvant Tamoxifen Mono-Therapy: A DBCG Study 1 2 3 1 3 Maria B. Lyng *, Anne-Vibeke Lænkholm , Rolf Søkilde , Karina H. Gravgaard , Thomas Litman , Henrik J. Ditzel1,4* 1 Institute of Molecular Medicine, University of Southern Denmark, Odense, Denmark, 2 Department of Pathology, Slagelse Hospital, Slagelse, Denmark, 3 Department of Biomarker Discovery, Exiqon A/S, Vedbæk, Denmark, 4 Department of Oncology, Odense University Hospital, Odense, Denmark Abstract Purpose: Despite the benefits of estrogen receptor (ER)-targeted endocrine therapies in breast cancer, many tumors develop resistance. MicroRNAs (miRNAs) have been suggested as promising biomarkers and we here evaluated whether a miRNA profile could be identified, sub-grouping ER+ breast cancer patients treated with adjuvant Tamoxifen with regards to probability of recurrence. Experimental Design: Global miRNA analysis was performed on 152 ER+ primary tumors from high-risk breast cancer patients with an initial discovery set of 52 patients, followed by two independent test sets (N = 60 and N = 40). All patients had received adjuvant Tamoxifen as mono-therapy (median clinical follow-up: 4.6 years) and half had developed distant recurrence (median time-to-recurrence: 3.5 years). MiRNA expression was examined by unsupervised hierarchical clustering and supervised analysis, including clinical parameters as co-variables. Results: The discovery set identified 10 highly significant miRNAs that discriminated between the patient samples according to outcome. However, the subsequent two independent test sets did not confirm the predictive potential of these miRNAs. A si