Medical Scientist Training Program, Washington University School of Medicine, St. Louis, Missouri.
Department of Surgery, Division of Public Health Sciences, Washington University School of Medicine, St. Louis, Missouri.
Cancer Prev Res (Phila). 2022 Jun 2;15(6):391-398. doi: 10.1158/1940-6207.CAPR-21-0253.
Mammographic breast density (MBD) is a risk factor for breast cancer, but its molecular basis is poorly understood. Growth factors stimulate cellular and epithelial proliferation and could influence MBD via these mechanisms. Studies investigating the associations of circulating growth factors with MBD have, however, yielded conflicting results especially in postmenopausal women. We, therefore, investigated the associations of plasma growth factor gene expression [insulin-like growth factor (IGF)-1, IGF-binding protein 3, FGF-1, FGF-12, TGFβ1 and bone morphogenetic protein (BMP)-2] with MBD in postmenopausal women. We used NanoString nCounter platform to quantify plasma growth factor gene expression and Volpara to evaluate volumetric MBD measures. We investigated the associations of growth factor gene expression with MBD using both multiple linear regression (fold change) and multinomial logistic regression models, adjusted for potential confounders. The mean age of the 368 women enrolled was 58 years (range, 50-64). In analyses using linear regression models, one unit increase in IGF-1 gene expression was associated with a 35% higher volumetric percent density (VPD, 1.35; 95% confidence interval (CI), 1.13-1.60; P = 0.001). There were suggestions that TGFβ1 gene expression was positively associated with VPD while BMP-2 gene expression was inversely associated with VPD, but these were not statistically significant. In analyses using multinomial logistic regression, TGFβ1 gene expression was 33% higher (OR = 1.33; 95% CI, 1.13-1.56; P = 0.0008) in women with extremely dense breasts than those with almost entirely fatty breasts. There were no associations between growth factor gene expression and dense volume or nondense volume. Our study provides insights into the associations of growth factors with MBD in postmenopausal women and requires confirmation in other study populations.
Mammographic breast density is a strong risk factor for breast cancer. Understanding its underlying biological mechanisms could have utility in breast cancer prevention.
乳腺密度（MBD）是乳腺癌的一个危险因素，但它的分子基础知之甚少。生长因子刺激细胞和上皮细胞增殖，并可能通过这些机制影响 MBD。然而，研究循环生长因子与 MBD 之间的关联的研究结果存在冲突，尤其是在绝经后妇女中。因此，我们研究了绝经后妇女血浆生长因子基因表达[胰岛素样生长因子（IGF）-1、IGF 结合蛋白 3、FGF-1、FGF-12、TGFβ1 和骨形态发生蛋白（BMP）-2]与 MBD 的关系。我们使用 NanoString nCounter 平台定量检测血浆生长因子基因表达，并用 Volpara 评估容积 MBD 测量值。我们使用多元线性回归（倍数变化）和多项逻辑回归模型，调整潜在混杂因素，研究生长因子基因表达与 MBD 的关系。纳入的 368 名女性的平均年龄为 58 岁（范围，50-64 岁）。在使用线性回归模型的分析中，IGF-1 基因表达增加一个单位，与容积百分比密度（VPD）增加 35%相关（1.35；95%置信区间（CI），1.13-1.60；P = 0.001）。有迹象表明 TGFβ1 基因表达与 VPD 呈正相关，而 BMP-2 基因表达与 VPD 呈负相关，但这些结果没有统计学意义。在使用多项逻辑回归的分析中，TGFβ1 基因表达在乳腺密度极高的女性中增加 33%（OR = 1.33；95%CI，1.13-1.56；P = 0.0008），而在乳腺密度几乎完全为脂肪的女性中则降低 33%。生长因子基因表达与致密体积或非致密体积之间没有关联。我们的研究提供了绝经后妇女生长因子与 MBD 之间关系的见解，需要在其他研究人群中得到证实。
乳腺密度是乳腺癌的一个强有力的危险因素。了解其潜在的生物学机制可能对乳腺癌预防具有实用价值。
