BACKGROUND Mammographic density (MD) is a strong breast cancer risk factor that reflects fibroglandular and adipose tissue composition, but its biologic underpinnings are poorly understood. Insulin-like growth factor binding proteins (IGFBPs) are markers that may be associated with MD given their hypothesized role in breast carcinogenesis. IGFBPs sequester IGF-I, limiting its bioavailability. Prior studies have found positive associations between circulating IGF-I and the IGF-I:IGFBP-3 ratio and breast cancer risk. We evaluated the associations of IGF-I, IGFBP-3, and six other IGFBPs with MD. METHODS Serum IGF measures were quantified in 296 women, ages 40-65, undergoing diagnostic image-guided breast biopsy. Volumetric density measures (MD-V) were assessed in pre-biopsy digital mammograms using single X-ray absorptiometry. Area density measures (MD-A) were estimated by computer-assisted thresholding software. Age, body mass index (BMI), and BMI2-adjusted linear regression models were used to examine associations of serum IGF measures with MD. Effect modification by BMI was also assessed. RESULTS IGF-I and IGFBP-3 were not strongly associated with MD after BMI adjustment. In multivariable analyses among premenopausal women, IGFBP-2 was positively associated with both percent MD-V (β = 1.49, p value = 0.02) and MD-A (β = 1.55, p value = 0.05). Among postmenopausal women, positive relationships between IGFBP-2 and percent MD-V (β = 2.04, p = 0.003) were observed; the positive associations between IGFBP-2 and percent MD-V were stronger among lean women (BMI < 25 kg/m2) (β = 5.32, p = 0.0002; p interaction = 0.0003). CONCLUSIONS In this comprehensive study of IGFBPs and MD, we observed a novel positive association between IGFBP-2 and MD, particularly among women with lower BMI. In concert with in vitro studies suggesting a dual role of IGFBP-2 on breast tissue, promoting cell proliferation as well as inhibiting tumorigenesis, our findings suggest that further studies assessing the role of IGFBP-2 in breast tissue composition, in addition to IGF-1 and IGFBP-3, are warranted.

中文翻译：

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进行图像引导诊断性乳腺穿刺活检的妇女中，循环胰岛素样生长因子-I和结合蛋白1-7与乳房X线照片密度的关系。

背景技术乳房X线照片密度（MD）是反映乳腺癌和脂肪组织组成的强烈乳腺癌风险因素，但对其生物学基础的了解却很少。胰岛素样生长因子结合蛋白（IGFBPs）是可能与MD相关的标志物，因为它们在乳腺癌的致癌作用中具有假定的作用。IGFBP螯合IGF-I，限制了其生物利用度。先前的研究发现循环中的IGF-I和IGF-I：IGFBP-3比例与乳腺癌风险呈正相关。我们评估了IGF-I，IGFBP-3和其他六个IGFBP与MD的关联。方法对296名年龄在40-65岁的接受影像学诊断性乳腺穿刺活检的女性进行血清IGF检测。使用单X射线吸收光度法在活检前的乳房X线照片中评估体积密度测量（MD-V）。面积密度测量（MD-A）通过计算机辅助阈值软件进行估算。年龄，体重指数（BMI）和BMI2调整的线性回归模型用于检查血清IGF测量值与MD的关联。还评估了BMI对效果的影响。结果BMI调整后，IGF-I和IGFBP-3与MD的相关性不强。在绝经前妇女的多变量分析中，IGFBP-2与MD-V百分比（β= 1.49，p值= 0.02）和MD-A（β= 1.55，p值= 0.05）均呈正相关。在绝经后妇女中，观察到IGFBP-2与MD-V百分比呈正相关（β= 2.04，p = 0.003）。在瘦弱的女性中（BMI <25 kg / m2），IGFBP-2与MD-V百分比之间的正相关性较强（β= 5.32，p = 0.0002； p相互作用= 0.0003）。结论在对IGFBPs和MD的全面研究中，我们观察到了IGFBP-2和MD之间的新型正相关性，特别是在BMI较低的女性中。与表明IGFBP-2在乳腺组织中具有双重作用，促进细胞增殖以及抑制肿瘤发生的体外研究相一致，我们的研究结果表明，除IGF-I外，进一步的研究评估了IGFBP-2在乳腺组织成分中的作用。保证1和IGFBP-3。