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: 8445007
• 负责人: JOANNE F DORGAN
• 金额: $ 2.72万
• 依托单位: RESEARCH INST OF FOX CHASE CAN CTR
• 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 2013-07-01
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8445007
• 关键词: 10 year old; Adolescence; Adolescent; Age; Age at Menarche; Androgens; Behavior Therapy; Binding; Biological Markers; Blood; Breast; Breast Cancer Risk Factor; Child; Collection; Control Groups; Data; Development; Dietary Intervention; Duct (organ) structure; Ductal Epithelium; Effectiveness of Interventions; Estradiol; Estrogens; 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; Measurement; 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; density; follow-up; girls; improved; malignant breast neoplasm; middle age; parity; prepuberty; public health relevance; reproductive; treatment as usual; young adult; young woman

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.

描述（由申请人提供）：背景：乳腺癌是一种荷尔蒙依赖的癌症，女性的血清雌激素和雄激素浓度与风险正相关。乳房密度是乳腺癌最强的危险因素之一，血清激素可能会通过影响乳腺密度来影响乳腺癌的风险。然而，绝经后内源性雌激素和雄激素浓度通常与乳房密度无关，尽管据报道了绝经前女性的正相关，但结果尚无定论。绝经前激素和乳房密度研究的大多数参与者都是40岁以上，并且远远超过了乳房发育时期，这主要发生在青春期，当时雌激素和孕酮调节乳房导管的伸长和分支，并且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，以前瞻性地评估青少年血清性激素水平与乳房密度的关联，该资源先前作为儿童饮食干预研究（DISC）和DISC06随访研究的一部分收集到的资源。目标/假设：我们假设青春期的性激素水平较高与成年年轻人的乳房密度更高有关。具体目的：主要目的是确定青少年血清雌二醇，睾丸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密集的乳房组织量有关。研究设计：将使用先前收集的DISC和DISC06随访研究的资源。椎间盘是一项随机对照试验，在该试验中，将LDL-胆固醇升高的健康，前8-10岁的孩子随机分配到行为干预措施中，以降低脂肪并增加纤维摄入量或通常的护理对照组。干预措施平均持续7年，并在参与者的平均年龄为16.7岁时被终止。收集血液以分析血清生物标志物，包括基线，1年，3年，5年和最后一次访问时的性激素。女性参与者的后续访问评估椎间盘干预对乳腺癌（包括乳腺癌）相关的生物标志物的长期影响，包括在参与者25-29岁时终止椎间盘后9年。我们将使用多级线性模型来评估177名圆盘参与者的青少年血清性激素水平与乳房密度的关联，他们在青少年期间在椎间盘中进行了更多的激素，并且在Disc06的随访访问中测量了乳房密度。意义：我们意识到没有先前评估青少年血清激素水平与年轻成年期的乳房密度的关联的先前研究。调查结果将为我们对青少年性激素水平对乳腺癌密度和乳腺癌风险的影响的理解重要。