Adolescent Sex Hormones and Breast Density in Young Women

描述（由申请人提供）：乳腺癌是一种激素依赖性癌症，女性血清雌激素和雄激素浓度与风险呈正相关。乳腺密度是乳腺癌的最大危险因素之一，血清激素可能通过对乳腺密度的影响而潜在地影响乳腺癌的风险。然而，绝经后内源性雌激素和雄激素浓度通常与乳腺密度无关，尽管有报道称绝经前妇女的雌激素和雄激素浓度与乳腺密度呈正相关，但结果尚无定论。大多数绝经前激素和乳腺密度研究的参与者年龄在40岁或以上，并且远远超过了乳房发育的时间，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，我们建议利用一个独特的机会，利用先前收集的儿童饮食干预研究（DISC）和DISC06随访研究的资源，前瞻性地评估青少年血清性激素水平与乳腺密度的关系。拟议的研究将大大提高我们对青春期血清性激素对乳腺密度的影响的理解，最终对乳腺癌风险的影响。目的/假设：我们假设青春期较高的性激素水平与成年早期较高的乳腺密度有关。具体目的：主要目的是确定青少年血清雌激素、雄激素和孕激素浓度是否与年轻成年女性乳腺密度百分比和致密乳腺组织体积相关。研究设计：将使用DISC和DISC06随访研究中先前收集的资源。DISC是一项随机对照试验，在试验中，健康的8-10岁低密度脂蛋白胆固醇升高的青春期前儿童被随机分配到减少脂肪和增加纤维摄入的行为干预组或常规护理对照组。干预平均持续了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，分析包括性激素在内的血清生物标志物。对女性参与者进行随访以评估长期影响

DESCRIPTION (provided by applicant): 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. The proposed research will greatly improve our understanding of the influence of serum sex hormones during adolescence on breast density and ultimately on breast cancer risk. 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 estrogen, androgen 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.