title: Insulin- and obesity-related variables in early-stage breast cancer: correlations and time course of prognostic associations.
abstract: OBJECTIVE
  To investigate patterns of prognostic associations over time of insulin- and obesity-related variables measured at diagnosis of early breast cancer (BC), focusing on whether the prognostic associations with distant recurrence and death changed over time.
  
  
  METHODS
  Five hundred thirty-five nondiabetic women with T1-3, N0-1, M0 invasive BC diagnosed from 1989 to 1996 were included in the study. Insulin-related variables included fasting insulin, Homeostasis Model Assessment, C-peptide, and glucose. Obesity-related variables included weight, body mass index (BMI), waist and hip circumference, and leptin. Correlations were examined using the Pearson correlation coefficient and prognostic associations using the Cox model.
  
  
  RESULTS
  There was evidence that associations of baseline insulin-related variables with distant recurrence and death were not constant over time; univariable adverse prognostic associations were significant only during the first 5 years (eg, insulin quartile 4 v 1: hazard ratio [HR], 2.32; 95% CI, 1.39 to 3.86; P < .001 for distant disease-free survival [DDFS]; and HR, 2.85; 95% CI, 1.48 to 5.50; P = .002 for overall survival [OS], with little attenuation of this pattern in multivariable analyses). In contrast, obesity-related variables (BMI, weight, leptin) exerted significant adverse univariable associations that were constant over time (eg, BMI quartile 4 v 2: HR, 1.40; 95% CI, 1.07 to 1.82 for DDFS; P = .014; and HR, 1.50; 95% CI, 1.16 to 1.93; P < .001 for OS); prognostic associations of leptin remained significant in multivariable analyses.
  
  
  CONCLUSIONS
  Baseline insulin- and obesity-related variables exert different patterns of prognostic associations over time in early BC.
authors.affiliation: Mount Sinai Hospital, 1284-600 University Ave, Toronto, Ontario M5G 1X5, Canada. pgoodwin@mtsinai.on.ca
authors.forename: Pamela J
authors.initials: PJ
authors.lastname: Goodwin
authors.forename: Marguerite
authors.initials: M
authors.lastname: Ennis
authors.forename: Kathleen I
authors.initials: KI
authors.lastname: Pritchard
authors.forename: Maureen E
authors.initials: ME
authors.lastname: Trudeau
authors.forename: Jarley
authors.initials: J
authors.lastname: Koo
authors.forename: Sara K
authors.initials: SK
authors.lastname: Taylor
authors.forename: Nicky
authors.initials: N
authors.lastname: Hood
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D015992:Body Mass Index; D001943:Breast Neoplasms / Q000097:blood* / Q000473:pathology; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007328:Insulin / Q000097:blood*; D020738:Leptin / Q000097:blood; D008875:Middle Aged; D009367:Neoplasm Staging; D009765:Obesity / Q000097:blood / Q000503:physiopathology*; D011379:Prognosis; D012307:Risk Factors
chemical_list: D007328:Insulin; D020738:Leptin