P4-11-02: Insulin-Like Growth Factor-1 (IGF-1), Insulin-Like Growth Factor Binding Protein-3 (IGFBP-3) and Lobule Type among Women in the Nurses' Health Study II (NHS II).

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Abstract In a previous analysis of women enrolled in NHSII, we found that among women diagnosed with benign breast disease (BBD), those with predominant type 1/no type 3 lobules were at lower risk of subsequent breast cancer compared to women with other lobule types. Additionally, studies in animal models suggest that higher levels of IGF-1, a polypeptide hormone involved in the proliferation/differentiation of normal mammary epithelium, may inhibit involution of breast lobules. However, the interaction between IGF-1 levels and lobule types in determining breast cancer risk has not been previously evaluated. Therefore, we examined the association between IGF-1 levels and lobule type among women with BBD. Methods: We conducted a cross-sectional study among 484 women in NHSII with biopsy-confirmed BBD between 1993–2001 who had blood samples available for determining levels of IGF-1 and IGFBP-3. A pathologist, blinded to exposure status, classified lobule type on biopsy slides according to the number of acini per lobule (type 1 < 12; type 2∼50; type 3∼80 acini). Lobule type was classified into (1) predominant type 1/no type 3 lobules or (2) other lobule types. Multivariate logistic models were used to assess the associations between plasma IGF-1, IGFBP-3, and IGF-1/IGFBP-3 levels with lobule type. Models were adjusted for age, IGF-1 batch and additional potential confounders in secondary analyses. Results: In univariate analyses, older age at biopsy, higher body mass index, postmenopausal status, nulliparity, and lower IGF-1 levels were associated with predominant type1/no type 3 lobules (p<0.05). In multivariate logistic models adjusting for age, higher IGF-1 levels were associated with a decreased risk of predominant type 1/no type 3 lobules (OR quartile 4 vs. quartile 1 = 0.35, 95%CI: 0.15−0.81). Greater IGF-1/IGFBP-3 ratio was also associated with a decreased risk of predominant type1/no type 3 lobules (OR quartile 4 vs. quartile 1 = 0.24, 95%CI: 0.10−0.57). These associations persisted, though were slightly attenuated, in models adjusting for additional potential confounders. Conclusion: Higher IGF-1 levels and greater IGF-1/IGFBP-3 ratios are associated with a decreased risk of predominant type 1 lobules/no type 3 lobules among women with BBD in the NHSII. Whether this association contributes to the mechanism by which IGF-1 confers an elevated breast cancer risk requires further investigation. Acknowledgements: This work was supported by T32 CA09001-35 CA124865, R01 CA050385, and the Breast Cancer Research Foundation Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P4-11-02.