INSULIN AND RELATED FACTORS IN PREMENOPAUSAL BREAST-CANCER RISK

Background: Insulin and insulin-like growth factor I (IGF-I) are impor tant mitogens in vitro and in vivo. It has been hypothesized that thes e factors may play an important role in the development of breast canc er. Methods: A case-control study comparing plasma insulin levels in 9 9 premenopausal women with newly diagnosed node-negative invasive carc inoma of the breast and 99 age-matched controls with incident biopsied nonproliferative breast disease (NP) was conducted. Women with known diabetes were excluded. Results: For the entire study group, mean age was 42.6 +/- 5.1 years and mean weight was 62.9 +/- 10.3 kg. After adj ustment for age and weight, elevated insulin levels were significantly associated with breast cancer, Odds Ratio (OR) for women in the highe st insulin quintile versus the lowest quintile = 2.83 (95% Confidence Interval [CI] 1.22-6.58). There were no statistically significant diff erences between cases and controls for IGF-I and IGFBP-1 levels. Howev er, after adjustment for age, the association between plasma levels of insulin-like growth factor binding protein 3 (IGFBP-3) and breast can cer approached statistical significance; OR for highest quintile versu s lowest quintile of IGFBP-3 being 2.05 (95% CI, 0.93-4.53). All resul ts were independent of diet and other known risk factors for breast ca ncer. Conclusion: Circulating insulin levels and possibly IGFBP-3 leve ls are elevated in women with premenopausal breast cancer. This associ ation may reflect an underlying syndrome of insulin resistance that is independent of obesity.