A cross‐sectional investigation of breast density and insulin‐like growth factor I

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Abstract
Our study investigated the association of breast cancer risk as assessed by mammographic density with insulin‐like growth factor I (IGF‐I) and one of its binding proteins (IGFBP‐3) in healthy premenopausal women with different ethnic backgrounds. In a cross‐sectional design, we analyzed the baseline mammograms and fasting serum samples (collected 5 days after ovulation) of premenopausal women entering a nutritional intervention. Serum concentrations of IGF‐I and IGFBP‐3 were measured by double‐antibody ELISA. Mammographic densities were assessed using a computer‐assisted method. We calculated Spearman correlation coefficients between mammographic characteristics and analytes and estimated means of mammographic characteristics by quartiles of IGF‐I and IGFBP‐3 while adjusting for age, body mass index (BMI) and reproductive factors. In this group of 240 women, IGF‐I, IGFBP‐3 and percent densities did not differ significantly by ethnicity. Whereas mammographic densities were not associated with IGF‐I, we found an inverse relation with IGFBP‐3 (rs = ‐0.15, p = 0.02) and a positive association with the IGF‐I/IGFBP‐3 ratio (rs = 0.13, p = 0.04). The size of the dense areas was not associated with the analytes, but the size of the nondense areas was correlated directly with IGFBP‐3 (rs = 0.20, p = 0.002) and inversely with the molar ratio (rs = −0.19, p = 0.004). These associations were limited to women with a BMI of less than 25 kg/m2. These results suggest that the balance of circulating IGF‐I and IGFBP‐3 levels may influence the growth of the fatty part of the breast more than the epithelial and stromal breast tissue, but the exact mechanism of action needs to be explored in more detail.