title: Prognostic value of metabolic response in breast cancer patients receiving neoadjuvant chemotherapy.
abstract: BACKGROUND
  Today's clinical diagnostic tools are insufficient for giving accurate prognosis to breast cancer patients. The aim of our study was to examine the tumor metabolic changes in patients with locally advanced breast cancer caused by neoadjuvant chemotherapy (NAC), relating these changes to clinical treatment response and long-term survival.
  
  
  METHODS
  Patients (n = 89) participating in a randomized open-label multicenter study were allocated to receive either NAC as epirubicin or paclitaxel monotherapy. Biopsies were excised pre- and post-treatment, and analyzed by high resolution magic angle spinning magnetic resonance spectroscopy (HR MAS MRS). The metabolite profiles were examined by paired and unpaired multivariate methods and findings of important metabolites were confirmed by spectral integration of the metabolite peaks.
  
  
  RESULTS
  All patients had a significant metabolic response to NAC, and pre- and post-treatment spectra could be discriminated with 87.9%/68.9% classification accuracy by paired/unpaired partial least squares discriminant analysis (PLS-DA) (p < 0.001). Similar metabolic responses were observed for the two chemotherapeutic agents. The metabolic responses were related to patient outcome. Non-survivors (< 5 years) had increased tumor levels of lactate (p = 0.004) after treatment, while survivors (≥ 5 years) experienced a decrease in the levels of glycine (p = 0.047) and choline-containing compounds (p ≤ 0.013) and an increase in glucose (p = 0.002) levels. The metabolic responses were not related to clinical treatment response.
  
  
  CONCLUSIONS
  The differences in tumor metabolic response to NAC were associated with breast cancer survival, but not to clinical response. Monitoring metabolic responses to NAC by HR MAS MRS may provide information about tumor biology related to individual prognosis.
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: Guro F
authors.initials: GF
authors.lastname: Giskeødegård
authors.forename: Tone F
authors.initials: TF
authors.lastname: Bathen
authors.forename: Beathe
authors.initials: B
authors.lastname: Sitter
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: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000175:diagnosis / Q000188:drug therapy* / Q000378:metabolism*; D017024:Chemotherapy, Adjuvant; D015331:Cohort Studies; D015251:Epirubicin / Q000627:therapeutic use; D005260:Female; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008875:Middle Aged; D015999:Multivariate Analysis; D020360:Neoadjuvant Therapy; D017239:Paclitaxel / Q000627:therapeutic use; D011379:Prognosis; D016019:Survival Analysis
chemical_list: D000970:Antineoplastic Agents; D015251:Epirubicin; D017239:Paclitaxel