title: Increased expression of miR-126 and miR-10a predict prolonged relapse-free time of primary oestrogen receptor-positive breast cancer following tamoxifen treatment.
abstract: BACKGROUND
  Adjuvant tamoxifen is a valid treatment option for women with oestrogen receptor (ER)-positive breast cancer. However, up to 40% of patients experience distant or local recurrence or die. MicroRNAs have been suggested to be important prognosticators in breast cancer. This study aims to identify microRNAs with the potential to predict tamoxifen response.
  
  
  METHODS
  We performed a global microRNA screen (1105 human microRNAs) in primary tumours of six matched pairs of postmenopausal, ER-positive breast cancer patients treated with tamoxifen, who were either recurrence free or had developed a recurrence (median follow up: 8.84 years; range: 1.28-12.7 years). Patients of this discovery set and the 81 patients of the validation set (median follow up: 8.64 years; range: 0.21-19.85 years) were treated at the Robert Bosch Hospital, Stuttgart, Germany, between 1986 and 2005.
  
  
  RESULTS
  Out of the top 20 deregulated microRNAs (12 up-regulated, eight down-regulated) miR-126 (Hazard Ratio (HR) = 0.56, 95% confidence interval (CI): 0.38-0.83; Holm-adj. P = 0.022) and miR-10a (HR = 0.53, 95% CI: 0.33-0.85; Holm-adj. P = 0.031) were identified as significant predictors of tamoxifen outcome by multivariate Cox regression analysis in the independent validation set of 81 postmenopausal, ER-positive patients. Kaplan-Meier survival analyses based on cut-offs determined by receiver operating characteristics curves confirmed that a higher expression of miR-126 and miR-10a in the patients tumour was associated with longer relapse-free time (log-rank P = 0.037, P<0.0001, respectively).
  
  
  CONCLUSIONS
  Our data suggest that miR-126 and miR-10a are independent predictors for tumour relapse in early postmenopausal breast cancer patients treated with adjuvant tamoxifen.
authors: Dr. Margarete Fischer-Bosch-Institute of Clinical Pharmacology, Stuttgart, Germany; University Tuebingen, Tuebingen, Germany.
authors: Reiner
authors: R
authors: Hoppe
authors: Joanna
authors: J
authors: Achinger-Kawecka
authors: Stefan
authors: S
authors: Winter
authors: Peter
authors: P
authors: Fritz
authors: Wing-Yee
authors: WY
authors: Lo
authors: Werner
authors: W
authors: Schroth
authors: Hiltrud
authors: H
authors: Brauch
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000235:genetics*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000401:mortality; D016022:Case-Control Studies; D017024:Chemotherapy, Adjuvant; D018572:Disease-Free Survival; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D017698:Postmenopause; D011379:Prognosis; D011960:Receptors, Estrogen / Q000378:metabolism; D012008:Recurrence; D012189:Retrospective Studies; D013629:Tamoxifen / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D018931:Antineoplastic Agents, Hormonal; D014408:Biomarkers, Tumor; C547183:MIRN10 microRNA, human; C527111:MIRN126 microRNA, human; D035683:MicroRNAs; D011960:Receptors, Estrogen; D013629:Tamoxifen
keywords: Breast cancer; MicroRNA; Outcome; Tamoxifen; Tamoxifen resistance