Fasting Insulin and Outcome in Early-Stage Breast Cancer:
Results of a Prospective Cohort Study

Journal of Clinical Oncology, v.20, i.1 Jan02

From the Department of Medicine, Department of Pathology and Laboratory Medicine, and Department of Surgery, Division of Clinical Epidemiology at the Samuel Lunenfeld Research Institute, Mount Sinai Hospital; Toronto-Sunnybrook Regional Cancer Centre; Sunnybrook and Women’s College Health Sciences Centre; St Michael’s Hospital; and University of Toronto, Toronto, Ontario, Canada.

Address reprint requests Pamela J. Goodwin, MD, Mount Sinai Hospital, 600 University Ave, Ste 1284, Toronto, Ontario M5G 1X5, Canada; email: pgoodwin@mtsinai.on.ca.

PURPOSE:
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.

PATIENTS AND 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.

CONCLUSION:
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