Serum IGFBP-2 and Risk of Atypical Hyperplasia of the Breast

Atypical hyperplasia of the breast (AH) is associated with increased risk of subsequent invasive breast cancer, yet little is known about the etiology of AH. Insulin-like growth factor binding protein 2 (IGFBP-2) may contribute to the development of AH due to its proliferative effects on mammary tissue. We conducted a nested case-control study of postmenopausal women enrolled in Women's Health Initiative-Clinical Trial. Cases were 275 women who developed incident AH during follow-up, individually (1: 1) matched to controls. Levels of IGFBP-2 were determined from fasting serum collected at baseline. Multivariable conditional logistic regression models were used to estimate odds ratios for the association of IGFBP-2 with risk of AH. Serum IGFBP-2 was associated with a nonsignificant decrease in risk for AH, when comparing the highest quartile to lowest quartile (OR = 0.65; 95% CI = 0.32-1.31). This decrease in risk was most evident when analyses were restricted to nondiabetic, nonusers of hormone therapy (OR = 0.33, 95% CI = 0.13-0.86, p_trend = 0.06) and nondiabetic women who were overweight or obese (OR = 0.43, 95% CI = 0.18-1.03, p_trend = 0.05). Results from this study provide some support for an inverse association between serum IGFBP2 levels and risk of AH, particularly in nondiabetic women who are overweight or obese. Further studies are required to confirm these results.