Serum IGF-1 and IGFBP-3 and risk of fibrocystic breast conditions among women in the Chinese breast self-examination trial.

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Insulin-like growth factor-1 (IGF-1) is involved in cellular proliferation, and it binds with high affinity to IGF binding protein-3 (IGFBP-3). A case-control study of serum IGF-1 and IGFBP-3 in relation to fibrocystic breast conditions (FC) was conducted using participants in a randomized trial of breast self-examination in Shanghai, China that included female members of the Shanghai Textile Industry Bureau ages 30–64 years. For the case-control study, all women biopsied between 1995 and 2000 who were found to have FC were included as cases (n=540), and 688 women free of FC were frequency matched to the cases by five-year age groups as controls. Immunoradiometric assay kits (Diagnostic System Laboratories, Inc., Webster, TX) were used to measure serum IGF-1 and IGFBP-3. Quartiles of each, as well as their molar ratio, were calculated from distributions in the control women. Analyses were adjusted for age and assay batch; other factors, such as body mass index, weight, and physical activity, did not alter the results. Relative to the lowest fourth, odds ratios (ORs) and 95% confidence intervals (CIs) for the risk of FC for increasing fourths of the IGF-1 distribution were 1.5 (1.0–2.2), 1.4 (0.9–2.1), and 2.3 (1.6–3.3), respectively. After further adjustment for IGFBP-3, the ORs and 95% CIs were 1.3 (0.8–1.9), 1.1 (0.7–1.7), and 1.7 (1.1–2.6), respectively. A similar association was seen for IGFBP-3 (ORs, 95% CIs: 1.7 (1.2–2.4), 1.7 (1.2–2.5), and 2.3 (1.6–3.2); after further adjustment for IGF-1: 1.5 (1.0–2.2), 1.5 (1.0–2.2), and 1.8 (1.2–2.7)). A high IGF-1/IGFBP-3 ratio was also associated with an increased risk (ORs, 95% CIs: 1.1 (0.8–1.7), 1.3 (0.9–1.9), and 1.9 (1.3–2.9)). The results for IGF-1 and IGF-1/IGFBP-3 were stronger among post-menopausal women (ORs, 95% CIs: 1.6 (0.8–3.1), 1.9 (0.9–4.1), and 3.0 (1.3–6.7) for IGF-1; and 1.2 (0.7–2.3), 1.6 (0.7–3.3), and 2.7 (1.1–6.5) for IGF-1/IGFBP-3), although the results for IGFBP-3 were not (ORs, 95% CIs: 1.1 (0.5–2.4), 1.8 (0.9–3.9), and 1.5 (0.8–3.0)). Among the 320 women for whom enough breast biopsy tissue was available to determine proliferative status according to the scheme of Stalsberg (Int J Cancer, 71: 333–9, 1997), 177 had proliferative elements and 143 lacked signs of cellular proliferation. The risk of developing FC associated with IGF-1 and IGF-1/IGFBP-3 was particularly strong among women with proliferation (ORs, 95% CIs: 2.5 (1.3–5.0), 2.8 (1.4–5.5), and 4.7 (2.4–9.2) for IGF-1; and 2.4 (1.3–4.8), 2.1 (1.0–4.2), and 4.6 (2.3–9.2) for IGF-1/IGFBP-3). This study suggests that IGF-1, IGFBP-3 and their molar ratio may contribute to the development of FC, particularly among post-menopausal women and for proliferative FC. Further studies to explore these relationships are needed.