title: Metabolic characterization of triple negative breast cancer.
abstract: BACKGROUND
  The aims of this study were to characterize the metabolite profiles of triple negative breast cancer (TNBC) and to investigate the metabolite profiles associated with human epidermal growth factor receptor-2/neu (HER-2) overexpression using ex vivo high resolution magic angle spinning magnetic resonance spectroscopy (HR MAS MRS). Metabolic alterations caused by the different estrogen receptor (ER), progesterone receptor (PgR) and HER-2 receptor statuses were also examined. To investigate the metabolic differences between two distinct receptor groups, TNBC tumors were compared to tumors with ER(pos)/PgR(pos)/HER-2(pos) status which for the sake of simplicity is called triple positive breast cancer (TPBC).
  
  
  METHODS
  The study included 75 breast cancer patients without known distant metastases. HR MAS MRS was performed for identification and quantification of the metabolite content in the tumors. Multivariate partial least squares discriminant analysis (PLS-DA) modeling and relative metabolite quantification were used to analyze the MR data.
  
  
  RESULTS
  Choline levels were found to be higher in TNBC compared to TPBC tumors, possibly related to cell proliferation and oncogenic signaling. In addition, TNBC tumors contain a lower level of Glutamine and a higher level of Glutamate compared to TPBC tumors, which indicate an increase in glutaminolysis metabolism. The development of glutamine dependent cell growth or "Glutamine addiction" has been suggested as a new therapeutic target in cancer. Our results show that the metabolite profiles associated with HER-2 overexpression may affect the metabolic characterization of TNBC. High Glycine levels were found in HER-2(pos) tumors, which support Glycine as potential marker for tumor aggressiveness.
  
  
  CONCLUSIONS
  Metabolic alterations caused by the individual and combined receptors involved in breast cancer progression can provide a better understanding of the biochemical changes underlying the different breast cancer subtypes. Studies are needed to validate the potential of metabolic markers as targets for personalized treatment of breast cancer subtypes.
authors.affiliation: Department of Circulation and Medical Imaging, Norwegian University of Science and Technology (NTNU), Trondheim, Norway. maria.d.cao@ntnu.no.
authors.forename: Maria D
authors.initials: MD
authors.lastname: Cao
authors.forename: Santosh
authors.initials: S
authors.lastname: Lamichhane
authors.forename: Steinar
authors.initials: S
authors.lastname: Lundgren
authors.forename: Anna
authors.initials: A
authors.lastname: Bofin
authors.forename: Hans
authors.initials: H
authors.lastname: Fjøsne
authors.forename: Guro F
authors.initials: GF
authors.lastname: Giskeødegård
authors.forename: Tone F
authors.initials: TF
authors.lastname: Bathen
mesh_terms: D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology; D016000:Cluster Analysis; D019295:Computational Biology; D005260:Female; D006801:Humans; D008207:Lymphatic Metastasis; D055442:Metabolome; D055432:Metabolomics / Q000379:methods; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D064726:Triple Negative Breast Neoplasms / Q000378:metabolism* / Q000473:pathology