title: Use of dynamic contrast-enhanced MR imaging to predict survival in patients with primary breast cancer undergoing neoadjuvant chemotherapy.
abstract: OBJECTIVE
  To investigate whether early changes in vascular parameters determined with dynamic contrast material-enhanced magnetic resonance (MR) imaging after two cycles of neoadjuvant chemotherapy (NAC) are predictive of disease-free and overall survival in primary breast cancer.
  
  
  METHODS
  Institutional ethics approval and informed consent were obtained. Patients with primary breast cancer (median age, 45 years; age range, 22-70 years) recruited from January 2001 to September 2008 underwent dynamic contrast-enhanced MR imaging before and after two cycles of NAC. Quantitative and semiquantitative kinetic parameters were calculated, including the volume transfer constant (K(trans)) and the initial area under the gadolinium concentration-time curve over 60 seconds (IAUGC(60)). Cut points optimized to the receiver operating characteristic curve were used to dichotomize MR imaging data for Kaplan-Meier survival analysis. MR imaging parameters and known prognostic indicators in primary breast cancer were correlated with disease-free and overall survival by using the Cox proportional hazards model for univariate and multivariate analyses.
  
  
  RESULTS
  MR imaging was performed before (n = 62) and after (n = 58) two cycles of NAC. The median follow-up time was 43.9 months for disease-free survival and 60.3 months for overall survival. There were 28 recurrences; 26 patients had distant metastases (two had additional local recurrence) and two had local recurrence only. There were 20 deaths, all of which were related to breast cancer. At univariate analysis, progesterone receptor status, the type of surgery performed, higher posttreatment K(trans) (P = .048), and larger posttreatment IAUGC(60) (P = .035) were significant predictors of worse disease-free survival. At multivariate analysis, progesterone receptor status (P = .002) and mean transit time (P = .025) were significant predictors of disease-free survival. Univariate analysis showed that clinical tumor stage (P = .005), progesterone receptor status (P = .025), and type of surgery performed (P = .017) were significant predictors of overall survival. Higher posttreatment K(trans) (P = .043), larger IAUGC(60) (P = .029), and larger tumor size at posttreatment MR imaging were predictive of worse overall survival (P = .018). Of these variables, K(trans) remained an independent indicator of overall survival (P = .038).
  
  
  CONCLUSIONS
  Higher posttreatment tumor vascularization as depicted with dynamic contrast-enhanced MR imaging may be associated with higher recurrence and lower survival rates. Dynamic contrast-enhanced MR imaging parameters, in conjunction with traditional prognostic factors, have the potential to be prognostic biomarkers for disease-free and overall survival in primary breast cancer.
authors.affiliation: Academic Oncology Unit, Mount Vernon Cancer Centre, Rickmansworth Rd, Northwood, Middlesex, HA6 2RN, England. soniali@gmail.com
authors.forename: Sonia P
authors.initials: SP
authors.lastname: Li
authors.forename: Andreas
authors.initials: A
authors.lastname: Makris
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Beresford
authors.forename: N Jane
authors.initials: NJ
authors.lastname: Taylor
authors.forename: Mei-Lin W
authors.initials: ML
authors.lastname: Ah-See
authors.forename: J James
authors.initials: JJ
authors.lastname: Stirling
authors.forename: James A
authors.initials: JA
authors.lastname: d'Arcy
authors.forename: David J
authors.initials: DJ
authors.lastname: Collins
authors.forename: Robert
authors.initials: R
authors.lastname: Kozarski
authors.forename: Anwar R
authors.initials: AR
authors.lastname: Padhani
mesh_terms: D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality*; D017024:Chemotherapy, Adjuvant / Q000401:mortality; D003287:Contrast Media; D004739:England; D005260:Female; D019786:Gadolinium DTPA; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000706:statistics & numerical data*; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D015995:Prevalence; D011379:Prognosis; D018570:Risk Assessment / Q000379:methods; D012307:Risk Factors; D016019:Survival Analysis; D015996:Survival Rate; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D003287:Contrast Media; D019786:Gadolinium DTPA