title: Long non-coding RNA expression profiles predict metastasis in lymph node-negative breast cancer independently of traditional prognostic markers.
abstract: BACKGROUND
  Patients with clinically and pathologically similar breast tumors often have very different outcomes and treatment responses. Current prognostic markers allocate the majority of breast cancer patients to the high-risk group, yielding high sensitivities in expense of specificities below 20%, leading to considerable overtreatment, especially in lymph node-negative patients. Seventy percent would be cured by surgery and radiotherapy alone in this group. Thus, precise and early indicators of metastasis are highly desirable to reduce overtreatment. Previous prognostic RNA-profiling studies have only focused on the protein-coding part of the genome, however the human genome contains thousands of long non-coding RNAs (lncRNAs) and this unexplored field possesses large potential for identification of novel prognostic markers.
  
  
  METHODS
  We evaluated lncRNA microarray data from 164 primary breast tumors from adjuvant naïve patients with a mean follow-up of 18 years. Eighty two patients who developed detectable distant metastasis were compared to 82 patients where no metastases were diagnosed. For validation, we determined the prognostic value of the lncRNA profiles by comparing the ability of the profiles to predict metastasis in two additional, previously-published, cohorts.
  
  
  RESULTS
  We showed that lncRNA profiles could distinguish metastatic patients from non-metastatic patients with sensitivities above 90% and specificities of 64-65%. Furthermore; classifications were independent of traditional prognostic markers and time to metastasis.
  
  
  CONCLUSIONS
  To our knowledge, this is the first study investigating the prognostic potential of lncRNA profiles. Our study suggest that lncRNA profiles provide additional prognostic information and may contribute to the identification of early breast cancer patients eligible for adjuvant therapy, as well as early breast cancer patients that could avoid unnecessary systemic adjuvant therapy. This study emphasizes the potential role of lncRNAs in breast cancer prognosis.
authors.affiliation: Department of Clinical Genetics, Odense University Hospital, Sdr. Boulevard 29, 5000, Odense C, Denmark. kristina.sorensen1@rsyd.dk.|Human Genetics, Clinical Institute, University of Southern Denmark, Sdr. Boulevard 29, 5000, Odense C, Denmark. kristina.sorensen1@rsyd.dk.
authors.forename: Kristina P
authors.initials: KP
authors.lastname: Sørensen
authors.affiliation: Department of Clinical Genetics, Odense University Hospital, Sdr. Boulevard 29, 5000, Odense C, Denmark. mads.thomasssen@rsyd.dk.|Human Genetics, Clinical Institute, University of Southern Denmark, Sdr. Boulevard 29, 5000, Odense C, Denmark. mads.thomasssen@rsyd.dk.
authors.forename: Mads
authors.initials: M
authors.lastname: Thomassen
authors.affiliation: Human Genetics, Clinical Institute, University of Southern Denmark, Sdr. Boulevard 29, 5000, Odense C, Denmark. qtan@health.sdu.dk.|Epidemiology, Institute of Public Health, University of Southern Denmark, J.B. Winsløvs Vej 9, 5000, Odense C, Denmark. qtan@health.sdu.dk.
authors.forename: Qihua
authors.initials: Q
authors.lastname: Tan
authors.affiliation: Department of Pathology, Odense University Hospital, J.B. Winsløvs Vej 15, 5000, Odense C, Denmark. martin.bak@rsyd.dk.
authors.forename: Martin
authors.initials: M
authors.lastname: Bak
authors.affiliation: Department of Oncology, Odense University Hospital, Sdr. Boulevard 29, 5000, Odense C, Denmark. soeren.cold@rsyd.dk.
authors.forename: Søren
authors.initials: S
authors.lastname: Cold
authors.affiliation: Department of Clinical Genetics, Odense University Hospital, Sdr. Boulevard 29, 5000, Odense C, Denmark. mark.burton@rsyd.dk.|Human Genetics, Clinical Institute, University of Southern Denmark, Sdr. Boulevard 29, 5000, Odense C, Denmark. mark.burton@rsyd.dk.
authors.forename: Mark
authors.initials: M
authors.lastname: Burton
authors.affiliation: Department of Clinical Genetics, Odense University Hospital, Sdr. Boulevard 29, 5000, Odense C, Denmark. martin.larsen@rsyd.dk.|Human Genetics, Clinical Institute, University of Southern Denmark, Sdr. Boulevard 29, 5000, Odense C, Denmark. martin.larsen@rsyd.dk.
authors.forename: Martin J
authors.initials: MJ
authors.lastname: Larsen
authors.affiliation: Department of Clinical Genetics, Odense University Hospital, Sdr. Boulevard 29, 5000, Odense C, Denmark. torben.kruse@rsyd.dk.|Human Genetics, Clinical Institute, University of Southern Denmark, Sdr. Boulevard 29, 5000, Odense C, Denmark. torben.kruse@rsyd.dk.
authors.forename: Torben A
authors.initials: TA
authors.lastname: Kruse
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers; D001706:Biopsy; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D055106:Genome-Wide Association Study; D006801:Humans; D008207:Lymphatic Metastasis; D008875:Middle Aged; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D016017:Odds Ratio; D011379:Prognosis; D062085:RNA, Long Noncoding / Q000235:genetics*; D015203:Reproducibility of Results; D015398:Signal Transduction; D059467:Transcriptome; D047368:Tumor Burden
chemical_list: D015415:Biomarkers; D062085:RNA, Long Noncoding