title: Fasting insulin and outcome in early-stage breast cancer: results of a prospective cohort study.
abstract: OBJECTIVE
  Insulin, a member of a family of growth factors that includes insulin-like growth factor (IGF)-I and IGF-II, exerts mitogenic effects on normal and malignant breast epithelial cells, acting via insulin and IGF-I receptors. Because of this and because of its recognized association with obesity, an adverse prognostic factor in breast cancer, we examined the prognostic associations of insulin in early-stage breast cancer.
  
  
  METHODS
  A cohort of 512 women without known diabetes, who had early-stage (T1 to T3, N0 to N1, and M0) breast cancer, was assembled and observed prospectively. Information on traditional prognostic factors and body size was collected, and fasting blood was obtained.
  
  
  RESULTS
  Fasting insulin was associated with distant recurrence and death; the hazard ratios and 95% confidence intervals (CI) for those in the highest (> 51.9 pmol/L) versus the lowest (< 27.0 pmol/L) insulin quartile were 2.0 (95% CI, 1.2 to 3.3) and 3.1 (95% CI, 1.7 to 5.7), respectively. There was some evidence to suggest that the association of insulin with breast cancer outcomes may be nonlinear. Insulin was correlated with body mass index (Spearman r = 0.59, P <.001), which, in turn, was associated with distant recurrence and death (P <.001). In multivariate analyses that included fasting insulin and available tumor- and treatment-related variables, adjusted hazard ratios for the upper versus lower insulin quartile were 2.1 (95% CI, 1.2 to 3.6) and 3.3 (95% CI, 1.5 to 7.0) for distant recurrence and death, respectively.
  
  
  CONCLUSIONS
  Fasting insulin level is associated with outcome in women with early breast cancer. High levels of fasting insulin identify women with poor outcomes in whom more effective treatment strategies should be explored.
authors.affiliation: Department of Medicine, Division of Clinical Epidemiology at the Samuel Lunenfeld Research Institute, Mount Sinai Hospital, 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: Yolanda
authors.initials: Y
authors.lastname: Madarnas
authors.forename: Warren
authors.initials: W
authors.lastname: Hartwick
authors.forename: Barry
authors.initials: B
authors.lastname: Hoffman
authors.forename: Nicky
authors.initials: N
authors.lastname: Hood
mesh_terms: D000328:Adult; D000368:Aged; D015992:Body Mass Index; D001943:Breast Neoplasms / Q000097:blood / Q000175:diagnosis* / Q000401:mortality; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007328:Insulin / Q000097:blood*; D008875:Middle Aged; D015999:Multivariate Analysis; D009864:Ontario / Q000453:epidemiology; D011379:Prognosis; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012307:Risk Factors; D015996:Survival Rate
chemical_list: D007328:Insulin