Serum insulin-like growth factor-I and breast cancer

Insulin-like growth factor I (IGF-I) is a systemic hormone with potent mito genic and anti-apoptotic properties, which could influence the proliferativ e behavior of normal breast cells. Limited epidemiological observations sug gest that the hormone may play a role in the etiology of breast cancer, esp ecially at pre-menopausal ages. In a prospective case-control study nested within a cohort of New York City women, IGF-I, IGF-binding protein 3 (IGFBP -3) and C peptide were measured in frozen serum samples from 172 premenopau sal and 115 post-menopausal subjects who were subsequently diagnosed with b reast cancer. Subjects were eligible if diagnosed 6 months or more after re cruitment into the study (7 to 120 months). Cohort members who matched the cases on age, menopausal status, date of blood sampling and day of menstrua l cycle at blood collection served as controls. Post-menopausal breast canc er was not associated with serum IGF-I, IGFBP-3 or C-peptide levels. Howeve r, the risk of breast cancer increased with increasing serum concentrations of ICF-I in pre-menopausal women. The odds ratio (OR) for the highest quar tile of IGF-I (>256 ng/ml) compared to the lowest (<168 ng/ml) was 1.60 [95 % confidence interval (CI) 0.91-2.81]. The OR decreased to 1.49 (95% CI 0.8 0-2.79) after adjustment for IGFBP-3. In analyses restricted to subjects wh o were pre-menopausal at the time of blood sampling and whose cancer was di agnosed before age 50, the top vs. bottom quartile OR increased appreciably to 2.30 (95% CI 1.07-4.94). Adjustment for IGFBP-3 reduced the OR to 1.90 (95% CI 0.82-4.42). There was no association between pre-menopausal breast cancer and IGFBP-3, IGF-I: IGFBP-3 ratio or non-fasting levels of C peptide . Elevated circulating levels of IGF-I may be an indicator of increased ris k of breast cancer occurring before age 50. (C) 2000 Wiley-Liss, Inc.