Frydenberg Hanne, Flote Vidar G, Iversen Anita, Finstad Sissi E, Furberg Anne-Sofie, Torjesen Peter A, Wilsgaard Tom, Schlichting Ellen, Ellison Peter T, Ursin Giske, Thune Inger
Department of Oncology, Oslo University Hospital HF, Ullevål, 0424, Oslo, Norway,
Cancer Causes Control. 2014 Jul;25(7):891-903. doi: 10.1007/s10552-014-0389-z. Epub 2014 May 7.
Mammographic density represents epithelial and stromal proliferation, while insulin-like growth factor (IGF)-1, insulin-like growth factor-binding protein-3, growth hormone (GH), and estrogen may influence cellular proliferation. However, whether these growth factors independently, or in combination with estrogen, influence mammographic density in premenopausal women remains unclear.
Growth factors were assessed in 202 ovulating premenopausal women participating in the Energy Balance and Breast Cancer Aspects-I study. Estrogen was assessed in serum, and daily in saliva, throughout a menstrual cycle. Computer-assisted mammographic density (Madena) was obtained from digitized mammograms (days 7-12 of the menstrual cycle). Associations between growth factors, estrogen, and mammographic density were studied in regression models.
Women with a mean age of 30.7 years had a mean percent mammographic density of 29.8%. Among women in the strata (above median split) of IGF-1 (>25 nmol/l) or GH (>0.80 mlU/l), we observed that an increase in salivary 17β-estradiol was associated with a higher odds for having higher percent mammographic density (>28.5%). The odds ratios (ORs) per standard deviation increase in 17β-estradiol were 1.81 [95% confidence interval (CI) 1.08-3.03] in the high IGF-1 stratum and 2.08 (95% CI 1.10-3.94) in the high GH stratum. Furthermore, women in these strata of growth factors (above median) who had an overall average 17β-estradiol above median (>16.8 pmol/l) had higher ORs for having higher percent mammographic density (>28.5%): IGF-1 4.13 (95 % CI 1.33-12.83) and GH 4.17 (95 % CI 1.41-12.28).
Growth factors, in combination with cycling estrogen, were associated with percent mammographic density, and may be of potential clinical relevance.
乳腺X线密度代表上皮和间质增生，而胰岛素样生长因子（IGF）-1、胰岛素样生长因子结合蛋白-3、生长激素（GH）和雌激素可能影响细胞增殖。然而，这些生长因子是独立作用，还是与雌激素共同作用来影响绝经前女性的乳腺X线密度，目前尚不清楚。
对参与能量平衡与乳腺癌研究项目一期的202名排卵正常的绝经前女性进行生长因子评估。在整个月经周期中，检测血清中的雌激素，并每天检测唾液中的雌激素。通过数字化乳腺X线片（月经周期第7至12天）获得计算机辅助乳腺X线密度（Madena）。在回归模型中研究生长因子、雌激素与乳腺X线密度之间的关联。
平均年龄为30.7岁的女性，其乳腺X线平均密度百分比为29.8%。在IGF-1（>25 nmol/l）或GH（>0.80 mIU/l）分层（中位数以上分组）的女性中，我们观察到唾液中17β-雌二醇水平升高与乳腺X线密度百分比更高（>28.5%）的几率增加有关。在高IGF-1分层中，17β-雌二醇每增加一个标准差，优势比（OR）为1.81 [95%置信区间（CI）1.08 - 3.03]；在高GH分层中，OR为2.08（95% CI 1.10 - 3.94）。此外，在这些生长因子分层（中位数以上）中，总体平均17β-雌二醇高于中位数（>16.8 pmol/l）的女性，其乳腺X线密度百分比更高（>28.5%）的OR更高：IGF-1为4.13（95% CI 1.33 - 12.83），GH为4.17（95% CI 1.41 - 12.28）。
生长因子与周期性雌激素共同作用，与乳腺X线密度百分比相关，可能具有潜在的临床意义。
