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。乳腺密度是乳腺癌最重要的危险因素之一，血清激素可能通过影响乳腺密度来影响乳腺癌风险。然而，绝经后内源性雌激素和雄激素浓度通常与乳腺密度无关，尽管据报道绝经前女性存在正相关关系，但结果尚无定论。大多数绝经前激素和乳房密度研究的参与者都在 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，此时雌激素和孕激素调节乳腺导管的伸长和分支，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，利用先前作为儿童饮食干预研究 (DISC) 和 DISC06 后续研究的一部分收集的资源，前瞻性评估青少年血清性激素水平与乳腺密度的关联。目标/假设：我们假设青春期较高的性激素水平与成年初期较高的乳房密度有关。具体目的：主要目的是确定青少年血清雌二醇、睾酮和黄体酮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：将使用先前在 DISC 和 DISC06 后续研究中收集的资源。 DISC 是一项随机对照试验，其中 LDL 胆固醇升高的青春期前 8-10 岁健康儿童被随机分配到降低脂肪和增加纤维摄入量的行为干预组或常规护理对照组。干预平均持续 7 年，并在参与者的平均年龄为 16.7 岁时终止。收集血液用于分析血清生物标志物，包括基线、第一年、第三年、第五年和最后一次就诊时的性激素。对女性参与者进行随访，以评估 DISC 干预对乳腺癌相关生物标志物（包括乳腺密度）的长期影响，在 DISC 终止后 9 年进行，当时参与者年龄为 25-29 岁。我们将使用多水平线性模型来评估 177 名 DISC 参与者的青少年血清性激素水平与乳腺密度的关联，这些参与者在 DISC 青春期的多个场合之一进行了激素测量，并且在 DISC06 随访中测量了乳腺密度。意义：据我们所知，之前没有任何研究按照我们的建议前瞻性地评估了青少年血清激素水平与青年期乳腺密度之间的关系。研究结果将有助于我们了解青少年性激素水平对乳腺密度和乳腺癌风险的影响。