Adolescent Sex Hormones and Breast Density in Young Women

背景：乳腺癌是一种激素依赖型癌症，女性的血清雌激素和雄激素浓度与风险呈正相关。乳房密度是乳腺癌的最大风险因素之一，血清激素可能通过影响乳房密度来潜在地影响乳腺癌风险。然而，绝经后内源性雌激素和雄激素浓度通常与乳房密度无关，尽管有报道称绝经前妇女存在正相关，但结果尚不确定。参与绝经前荷尔蒙和乳房密度研究的大多数人年龄都在40岁或以上，远远超过乳房发育的时间，乳房发育主要发生在青春期，此时雌激素和黄体酮调节乳房导管的伸长和分支，可能对乳房密度产生最大的影响。因此，我们建议利用先前在儿童饮食干预研究(DISC)和DISC06后续研究中收集的资源，利用一个独特的机会前瞻性地评估青春期血清性激素水平与乳房密度的关系。目的/假设：我们假设青春期较高的性激素水平与青年时期较大的乳房密度有关。具体目标：主要目的是确定青春期血清雌二醇、睾酮和孕酮浓度是否与年轻成年女性的乳房密度百分比和致密乳房组织体积有关。研究设计：将使用先前收集的光盘资料和DISC06后续研究。DISC是一项随机对照试验，将8-10岁低密度脂蛋白升高的健康青春期前儿童随机分配到行为干预组，以降低脂肪和增加纤维摄入量，或分配到常规护理对照组。干预平均持续7年，当参与者的平均年龄为16.7岁时终止。在基线、第1年、第3年、第5年和最后一次就诊时采集血液进行包括性激素在内的血清生物标志物分析。女性参与者的随访是在25-29岁的参与者在椎间盘终止9年后进行的，以评估椎间盘干预对乳腺癌相关生物标记物的长期影响，包括乳房密度。我们将使用多水平线性模型来评估177名盘参与者的青春期性激素水平与乳房密度的关系，这些参与者在青春期盘中多次测量激素，并在DISC06随访时测量乳房密度。意义：据我们所知，先前没有任何研究如我们所建议的那样，前瞻性地评估青春期血清激素水平与青年时期乳房密度的关系。研究结果将有助于我们更好地理解青春期性激素水平对乳房密度和乳腺癌风险的影响。

DESCRIPTION (provided by applicant): Background: Breast cancer is a hormonally dependent cancer and a woman's serum estrogen and androgen concentrations are positively associated with risk. Breast density is one of the strongest risk factors for breast cancer, and serum hormones could potentially influence breast cancer risk via effects on breast density. However, postmenopausal endogenous estrogen and androgen concentrations generally are not associated with breast density, and although positive associations have been reported for premenopausal women, results are inconclusive. Most of the participants in studies of premenopausal hormones and breast density were 40 years or older and well past the time of breast development, which occurs primarily during adolescence when estrogens and progesterone regulate elongation and branching of breast ducts and could have their greatest effects on breast density. Thus, we propose to take advantage of a unique opportunity to prospectively evaluate associations of adolescent serum sex hormone levels with breast density using resources previously collected as part of the Dietary Intervention Study in Children (DISC) and the DISC06 Follow-Up Study. Objectives/Hypothesis: We hypothesize that higher sex hormone levels during adolescence are associated with greater breast density in young adulthood. Specific Aims: Primary aims are to determine if adolescent serum estradiol, testosterone and progesterone concentrations are associated with percent breast density and volume of dense breast tissue in young adult women. Study Design: Previously collected resources in DISC and the DISC06 Follow-Up Study will be used. DISC was a randomized controlled trial in which healthy, prepubertal 8-10 year olds with elevated LDL-cholesterol were randomly assigned to a behavioral intervention to lower fat and increase fiber intake or to a usual care control group. The intervention continued for an average of 7 years and was terminated when participants' mean age was 16.7 years. Blood was collected for analysis of serum biomarkers including sex hormones at baseline, Year-1, Year-3, Year-5 and last visits. Follow-up visits for female participants to evaluate longer-term effects of the DISC intervention on biomarkers associated with breast cancer including breast density took place 9 years after termination of DISC when participants were 25-29 years old. We will use multilevel linear models to evaluate associations of adolescent serum sex hormone levels with breast density in 177 DISC participants who had hormones measured on one of more occasions during adolescence in DISC and who had breast density measured at the DISC06 follow-up visit. Significance: We are aware of no prior studies that have prospectively evaluated associations of adolescent serum hormone levels with breast density in young adulthood as we propose. Findings will add importantly to our understanding of the influence of adolescent sex hormone levels on breast density and breast cancer risk.