Fasting insulin and outcome in early-stage breast cancer: results of a prospective cohort study.
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.
Goodwin
Pamela J
PJ
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
Ennis
Marguerite
M
Pritchard
Kathleen I
KI
Trudeau
Maureen E
ME
Koo
Jarley
J
Madarnas
Yolanda
Y
Hartwick
Warren
W
Hoffman
Barry
B
Hood
Nicky
N
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
D007328:Insulin