title: Identification of a serum-detectable metabolomic fingerprint potentially correlated with the presence of micrometastatic disease in early breast cancer patients at varying risks of disease relapse by traditional prognostic methods.
abstract: BACKGROUND
  Prognostic tools in early breast cancer are inadequate. The evolving field of metabolomics may allow more accurate identification of patients with residual micrometastases.
  
  
  METHODS
  Forty-four early breast cancer patients with pre- and postoperative serum samples had metabolomic assessment by nuclear magnetic resonance. Fifty-one metastatic patients served as control. Differential clustering was identified and used to calculate individual early patient 'metabolomic risk', calculated as inverse distance of each early patient from the metastatic cluster barycenter. Metabolomic risk was compared with Adjuvantionline 10-year mortality assessment.
  
  
  RESULTS
  Innate serum metabolomic differences exist between early and metastatic patients. Preoperative patients were identified with 75% sensitivity, 69% specificity and 72% predictive accuracy. Comparison with Adjuvantionline revealed discordance. Of 21 patients assessed as high risk by Adjuvantionline, 10 (48%) and 6 (29%) were at high risk by metabolomics in pre- and postoperative settings, respectively. Of 23 low-risk patients by Adjuvantionline, 11 (48%) preoperative and 20 (87%) postoperative patients were at low risk by metabolomics.
  
  
  CONCLUSIONS
  This study identifies metabolomic discrimination between early and metastatic breast cancer. Micrometastatic disease may account for metabolomic misclassification of some early patients as metastatic. Metabolomics identifies more patients as low relapse risk compared with Adjuvantionline. Further exploration of this metabolomic fingerprint is warranted.
authors.affiliation: Department of Oncology, "Sandro Pitigliani" Medical Oncology Unit, Hospital of Prato, Istituto Toscano Tumori, Prato.
authors.forename: C
authors.initials: C
authors.lastname: Oakman
authors.affiliation: Magnetic Resonance Center (CERM), University of Florence, Sesto Fiorentino; FiorGen Foundation, Sesto Fiorentino, Italy.
authors.forename: L
authors.initials: L
authors.lastname: Tenori
authors.affiliation: Department of Oncology, "Sandro Pitigliani" Medical Oncology Unit, Hospital of Prato, Istituto Toscano Tumori, Prato.
authors.forename: W M
authors.initials: WM
authors.lastname: Claudino
authors.affiliation: Department of Oncology, "Sandro Pitigliani" Medical Oncology Unit, Hospital of Prato, Istituto Toscano Tumori, Prato.
authors.forename: S
authors.initials: S
authors.lastname: Cappadona
authors.affiliation: Magnetic Resonance Center (CERM), University of Florence, Sesto Fiorentino; FiorGen Foundation, Sesto Fiorentino, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Nepi
authors.affiliation: Department of Oncology, "Sandro Pitigliani" Medical Oncology Unit, Hospital of Prato, Istituto Toscano Tumori, Prato.
authors.forename: A
authors.initials: A
authors.lastname: Battaglia
authors.affiliation: Magnetic Resonance Center (CERM), University of Florence, Sesto Fiorentino.
authors.forename: P
authors.initials: P
authors.lastname: Bernini
authors.affiliation: Department of Oncology, "Sandro Pitigliani" Medical Oncology Unit, Hospital of Prato, Istituto Toscano Tumori, Prato.
authors.forename: E
authors.initials: E
authors.lastname: Zafarana
authors.affiliation: Magnetic Resonance Center (CERM), University of Florence, Sesto Fiorentino.
authors.forename: E
authors.initials: E
authors.lastname: Saccenti
authors.affiliation: Breast Cancer Medicine Service, Memorial Sloan-Kettering Cancer Center, New York, USA.
authors.forename: M
authors.initials: M
authors.lastname: Fornier
authors.affiliation: Breast Cancer Medicine Service, Memorial Sloan-Kettering Cancer Center, New York, USA.
authors.forename: P G
authors.initials: PG
authors.lastname: Morris
authors.affiliation: Department of Oncology, "Sandro Pitigliani" Medical Oncology Unit, Hospital of Prato, Istituto Toscano Tumori, Prato.
authors.forename: L
authors.initials: L
authors.lastname: Biganzoli
authors.affiliation: Magnetic Resonance Center (CERM), University of Florence, Sesto Fiorentino; Department of Chemistry, University of Florence, Sesto Fiorentino, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Luchinat
authors.affiliation: Magnetic Resonance Center (CERM), University of Florence, Sesto Fiorentino; Department of Chemistry, University of Florence, Sesto Fiorentino, Italy.
authors.forename: I
authors.initials: I
authors.lastname: Bertini
authors.affiliation: Department of Oncology, "Sandro Pitigliani" Medical Oncology Unit, Hospital of Prato, Istituto Toscano Tumori, Prato. Electronic address: adileo@usl4.toscana.it.
authors.forename: A
authors.initials: A
authors.lastname: Di Leo
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000097:blood*; D001943:Breast Neoplasms / Q000097:blood* / Q000473:pathology*; D055088:Early Detection of Cancer; D005260:Female; D006801:Humans; D055432:Metabolomics / Q000379:methods*; D008875:Middle Aged; D061206:Neoplasm Micrometastasis; D009364:Neoplasm Recurrence, Local / Q000097:blood*; D011379:Prognosis; D012306:Risk
chemical_list: D014408:Biomarkers, Tumor