Adolescent Sex Hormones and Breast Density in Young Women

年轻女性的青春期性激素和乳房密度

• 批准号: 8699449
• 负责人: JOANNE F DORGAN
• 金额: $ 5.92万
• 依托单位: UNIVERSITY OF MARYLAND BALTIMORE
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-02-01 至 2015-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8699449
• 关键词: 10 year old; Adolescence; Adolescent; Age; Age at Menarche; Androgens; Androstenedione; Behavior Therapy; Binding; Biological Markers; Blood; Breast; Breast Cancer Risk Factor; Child; Collection; Control Groups; Data; Dehydroepiandrosterone Sulfate; Development; Dietary Intervention; Duct (organ) structure; Ductal Epithelium; Effectiveness of Interventions; Estradiol; Estrogens; Estrone; Estrone-Sulfate; Fatty acid glycerol esters; Female; Fiber; Gonadal Steroid Hormones; Hormones; Intake; Intervention; Intervention Studies; LDL Cholesterol Lipoproteins; Linear Models; Long-Term Effects; Malignant Neoplasms; Mammary Gland Parenchyma; Measures; Menarche; Menopause; Menstrual cycle; Mitogens; Participant; Pathway interactions; Phase; Postmenopause; Pregnancy; Premenopause; Progesterone; Randomized; Randomized Controlled Clinical Trials; Randomized Controlled Trials; Reporting; Reproductive History; Research; Research Design; Resources; Risk; Risk Factors; Serum; Testosterone; Time; Visit; Woman; breast density; cancer risk; follow-up; girls; improved; malignant breast neoplasm; parity; prepuberty; reproductive; treatment as usual; young adult; young woman

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.

描述（由申请人提供）：乳腺癌是一种生殖依赖性癌症，女性血清雌激素和雄激素浓度与风险呈正相关。乳腺密度是乳腺癌最强的危险因素之一，血清激素可能通过影响乳腺密度而影响乳腺癌的风险。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，尽管绝经前妇女的相关性报道，结果是不确定的。绝经前激素和乳腺密度研究的大多数参与者年龄在40岁或以上，并且已经过了乳房发育的时间，乳房发育主要发生在青春期，此时雌激素和孕激素调节乳腺导管的伸长和分支，并可能对乳腺密度产生最大影响。因此，我们建议利用一个独特的机会，前瞻性地评估青少年血清性激素水平与乳腺密度的关联，使用以前收集的资源作为儿童饮食干预研究（DISC）和DISC 06随访研究的一部分。这项研究将大大提高我们对青春期血清性激素对乳腺密度和最终乳腺癌风险影响的理解。目的/假设：我们假设青春期较高的性激素水平与青年期较高的乳腺密度相关。具体目标：主要目的是确定青春期血清雌激素、雄激素和孕激素浓度是否与年轻成年女性的乳腺密度百分比和致密乳腺组织体积相关。研究设计：将使用先前在DISC和DISC 06随访研究中收集的资源。DISC是一项随机对照试验，在该试验中，健康的、青春期前的8-10岁的LDL胆固醇升高的儿童被随机分配到行为干预组，以降低脂肪和增加纤维摄入量，或常规护理对照组。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年和末次访视时采集血液用于分析血清生物标志物，包括性激素。对女性参与者进行随访，以评估 DISC干预与乳腺癌相关的生物标志物，包括乳腺密度，发生在DISC终止后9年，参与者年龄为25-29岁。我们将使用多水平线性模型来评估青少年血清性激素水平与177名DISC参与者的乳腺密度的相关性，这些参与者在DISC青春期期间多次测量激素，并在DISC 06随访时测量乳腺密度。重要性：据我们所知，以前没有研究前瞻性地评估青春期血清激素水平与成年早期乳腺密度的关系。研究结果将重要地增加我们对青春期性激素水平对乳腺密度和乳腺癌风险的影响的理解。