title: Predicting long-term survival and treatment response in breast cancer patients receiving neoadjuvant chemotherapy by MR metabolic profiling.
abstract: OBJECTIVE
  This study aimed to evaluate whether MR metabolic profiling can be used for prediction of long-term survival and monitoring of treatment response in locally advanced breast cancer patients during neoadjuvant chemotherapy (NAC).
  
  
  METHODS
  High resolution magic angle spinning (HR MAS) MR spectra of pre- and post-treatment biopsies from 33 patients were acquired. Tissue concentrations of choline-containing metabolites (tCho), glycine and taurine were assessed using electronic reference to access in vivo concentration (ERETIC) of the signal and receiver operating characteristic (ROC) curves was used to define their potential to predict patient survival and treatment response. The metabolite profiles obtained by HR MAS spectroscopy were related to long-term survival and treatment response by genetic algorithm partial least squares discriminant analysis (GA PLS-DA).
  
  
  RESULTS
  Different pre-treatment MR metabolic profiles characterized by higher levels of tCho and lower levels of lactate were observed in patients with long-term survival (≥5 years, survivors) compared to patients who died of cancer recurrence (<5 years, non-survivors). A significant decrease in glycerophosphocholine (GPC) post-treatment was associated with long-term survival (p = 0.046) and partial response (p = 0.014) to NAC. Long-term survival was best predicted by GPC using ROC analyses (sens. 66.7%, spec. 62.5%), while taurine had the best predictive value of treatment response (sens. 72.7%, spec. 63.2%). GA PLS-DA multivariate classification models successfully discriminated between survivors and non-survivors, resulting in 82.7% and 90.2% cross-validation (CV) classification accuracy, pre- and post-treatment, respectively. Classification of treatment response using GA PLS-DA was not successful for this patient cohort.
  
  
  CONCLUSIONS
  Our results demonstrate that HR MAS MR metabolic profiles consisting of important metabolic characteristics of breast cancer tumors could potentially assist the classification and prediction of long-term survival in locally advanced breast cancer patients, in addition to being used as an adjunct for evaluation of treatment response to NAC.
authors.affiliation: Department of Circulation and Medical Imaging, Norwegian University of Science and Technology (NTNU), 7489, Trondheim, Norway. maria.d.cao@ntnu.no
authors.forename: Maria D
authors.initials: MD
authors.lastname: Cao
authors.forename: Beathe
authors.initials: B
authors.lastname: Sitter
authors.forename: Tone F
authors.initials: TF
authors.lastname: Bathen
authors.forename: Anna
authors.initials: A
authors.lastname: Bofin
authors.forename: Per E
authors.initials: PE
authors.lastname: Lønning
authors.forename: Steinar
authors.initials: S
authors.lastname: Lundgren
authors.forename: Ingrid S
authors.initials: IS
authors.lastname: Gribbestad
mesh_terms: D000368:Aged; D000465:Algorithms; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001706:Biopsy; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D016002:Discriminant Analysis; D005260:Female; D005997:Glycerylphosphorylcholine / Q000378:metabolism; D006801:Humans; D016018:Least-Squares Analysis; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D055442:Metabolome; D008875:Middle Aged; D015999:Multivariate Analysis; D020360:Neoadjuvant Therapy; D012372:ROC Curve; D015203:Reproducibility of Results; D016019:Survival Analysis; D013654:Taurine / Q000378:metabolism; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D013654:Taurine; D005997:Glycerylphosphorylcholine