title: Hsa-miR-375 is a predictor of local control in early stage breast cancer.
abstract: BACKGROUND
  A long-term analysis by the Early Breast Cancer Trialist Group (EBCTG) revealed a strong correlation between local control and cancer-specific mortality. MicroRNAs (miRs), short (20-25 nucleotides) non-coding RNAs, have been described as prognosticators and predictors for breast cancer in recent years. The aim of the current study was to identify miRs that can predict local control after breast conserving therapy (BCT) in early stage breast cancer.
  
  
  RESULTS
  Clinical data of 46 early stage breast cancer patients with local relapse after BCT were selected from the institutional database. These patients were matched to 101 control patients showing identical clinical features but without local relapse. The study was conducted in two steps. (1) In the pilot study, 32 patients (16 relapses versus 16 controls) were screened for the most de-regulated microRNAs (= candidate microRNAs) in a panel of 1250 miRs by microarray technology. Eight miRs were found to be significantly de-regulated. (2) In the validation study, the candidate microRNAs were analyzed in an independent cohort of 115 patients (30 relapses versus 85 controls) with reverse transcription quantitative polymerase chain reaction (RT-qPCR). From these eight candidates, hsa-miR-375 could be validated. Its median fold change was 2.28 (Mann-Whitney U test, corrected p value = 0.008). In the log-rank analysis, high expression levels of hsa-miR-375 correlated with a significantly higher risk of local relapse (p = 0.003). In a multivariate analysis (forward stepwise regression) including established predictors and prognosticators, hsa-miR-375 was the only variable that was able to distinguish the statistical significance between relapse and control groups (raw p value = 0.000195 HR = 0.76, 95 % CI 0.66-0.88; corrected p value = 0.005).
  
  
  CONCLUSIONS
  Hsa-miR-375 predicts local control in patient with early stage breast cancer, especially in estrogen receptor α (ER-α)-positive patients. It can therefore serve as an additional molecular marker for treatment choice independently from known predictors and prognosticators. Validation in larger prospective studies is warranted.
authors.affiliation: Department of Radiation Oncology, Paracelsus Medical University, SALK, Müllner Hauptstraße 48, A-5020 Salzburg, Austria ; radART - Institute for Research and Development on Advanced Radiation Technologies, Paracelsus Medical University, Salzburg, Austria.
authors.forename: Franz
authors.initials: F
authors.lastname: Zehentmayr
authors.affiliation: Department of Pathology, Paracelsus Medical University, SALK, Salzburg, Austria.
authors.forename: Cornelia
authors.initials: C
authors.lastname: Hauser-Kronberger
authors.affiliation: radART - Institute for Research and Development on Advanced Radiation Technologies, Paracelsus Medical University, Salzburg, Austria ; Department of Pathology, Paracelsus Medical University, SALK, Salzburg, Austria.
authors.forename: Barbara
authors.initials: B
authors.lastname: Zellinger
authors.affiliation: Department of Pathology, Ludwig Maximilian University, Munich, Germany.
authors.forename: Falk
authors.initials: F
authors.lastname: Hlubek
authors.affiliation: Department of Pathology, Ludwig Maximilian University, Munich, Germany.
authors.forename: Claudia
authors.initials: C
authors.lastname: Schuster
authors.affiliation: Institute of Bioinformatics, Johannes Kepler University, Linz, Austria.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Bodenhofer
authors.affiliation: Department of Radiation Oncology, Paracelsus Medical University, SALK, Müllner Hauptstraße 48, A-5020 Salzburg, Austria.
authors.forename: Gerd
authors.initials: G
authors.lastname: Fastner
authors.affiliation: Department of Radiation Oncology, Paracelsus Medical University, SALK, Müllner Hauptstraße 48, A-5020 Salzburg, Austria ; radART - Institute for Research and Development on Advanced Radiation Technologies, Paracelsus Medical University, Salzburg, Austria.
authors.forename: Heinz
authors.initials: H
authors.lastname: Deutschmann
authors.affiliation: radART - Institute for Research and Development on Advanced Radiation Technologies, Paracelsus Medical University, Salzburg, Austria.
authors.forename: Philipp
authors.initials: P
authors.lastname: Steininger
authors.affiliation: Department of Gynecology and Obstetrics, Paracelsus Medical University, SALK, Salzburg, Austria.
authors.forename: Roland
authors.initials: R
authors.lastname: Reitsamer
authors.affiliation: Department of Gynecology and Obstetrics, Paracelsus Medical University, SALK, Salzburg, Austria.
authors.forename: Thorsten
authors.initials: T
authors.lastname: Fischer
authors.affiliation: Department of Radiation Oncology, Paracelsus Medical University, SALK, Müllner Hauptstraße 48, A-5020 Salzburg, Austria ; radART - Institute for Research and Development on Advanced Radiation Technologies, Paracelsus Medical University, Salzburg, Austria.
authors.forename: Felix
authors.initials: F
authors.lastname: Sedlmayer
mesh_terms: D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000175:diagnosis / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D005819:Genetic Markers; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D011379:Prognosis; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D005819:Genetic Markers; C540933:MIRN375 microRNA, human; D035683:MicroRNAs
keywords: Early stage breast cancer; Local control; MicroRNAs; Predictive markers; hsa-miR-375