Nipple Fluid Hormone Levels and Breast Cancer Risk

乳头液激素水平与乳腺癌风险

• 批准号: 7825331
• 负责人: SEEMA Ahsan KHAN
• 金额: $ 51.03万
• 依托单位: NORTHWESTERN UNIVERSITY AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-06-11 至 2012-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7825331
• 关键词: Age; Androgens; Androstenedione; Biological; Biological Assay; Biological Markers; Blood Circulation; Blood specimen; Breast; Breast Cancer Risk Factor; Case-Control Studies; Cathepsins; Chemoprevention; Clinical; Data; Disease; EGF gene; Endocrine; Environment; Enzymes; Epidemiologic Studies; Epidermal Growth Factor; Estradiol; Estrogens; Estrone; Estrone-Sulfate; Exposure to; Gonadal Steroid Hormones; Hand; Hormone Receptor; Hormone replacement therapy; Hormones; Inorganic Sulfates; Intervention; Link; Liquid substance; Malignant Neoplasms; Mammary Gland Parenchyma; Mammographic Density; Mammography; Measurement; Measures; Mediating; Menopausal Status; Menopause; Menstrual cycle; Methods; Newly Diagnosed; Nipples; Oral Contraceptives; Ovarian; Pattern; Phase; Phenotype; Pilot Projects; Postmenopause; Premenopause; Prevention; Prevention strategy; Preventive Intervention; Progesterone; Prostate-Specific Antigen; Proteins; Race; Research; Research Personnel; Risk; Risk Marker; Risk Reduction; Screening procedure; Serum; Steroids; Stratification; Subgroup; Surrogate Endpoint; TFF1 gene; Testing; Testosterone; Time; Tissues; Unspecified or Sulfate Ion Sulfates; Woman; Work; aged; base; cancer risk; candidate marker; case control; dehydroepiandrosterone; density; design; improved; interest; malignant breast neoplasm; nipple aspirate fluid; prevent; programs; response; risk benefit ratio; steroid hormone; tool; tumor

DESCRIPTION (provided by applicant): Lifetime exposure to sex steroids is a major contributor to breast cancer risk. The risk-benefit ratio of prevention strategies that target the endocrine axis would be significantly improved if it were possible to assess risk for hormone sensitive breast cancer. Nipple fluid hormone levels are attractive candidate markers of breast cancer risk. Our pilot studies provide preliminary data that nipple aspirate fluid (NAF) levels of sex steroids (estradiol and progesterone) are potential biomarkers of breast cancer risk in both pre and postmenopausal women. We show that these markers are significantly higher in NAF than in serum, are stable over time, and are biologically relevant, as reflected by the strong correlations of NAF estradiol levels with the content of estrogen response proteins in NAF. Additionally, we show that the hormone content of NAF reflects the systemic environment, since hormone levels rise with the use of hormone replacement therapy, are low in oral contraceptive users, and rise after cessation of oral contraceptives. Finally, preliminary analyses show, for the first time, a correlation of NAF estradiol and progesterone with estimated Gail risk. The primary hypothesis to be examined in this proposal is that NAF estradiol levels are markers of risk for hormone sensitive breast cancer. To accomplish this, we are proposing a case-control study of 600 women: 300 newly diagnosed breast cancer cases aged 40 to 60 from the Lynn Sage Breast Center, and 300 controls from the adjacent Mammography Screening Center of Northwestern. Cases and controls will be matched for age and menopausal status. We will obtain NAF, blood samples, and mammographic density measurements. NAF assays will include sex steroids (estradiol and progesterone), their precursors (estrone, estrone sulphate, androstenedione dehydroepiandrosterone and testosterone) and related proteins (epidermal growth factor, cathepsin D, pS2, and prostate specific antigen). We will perform sub-analyses to examine the effect of specific breast cancer risk factors, menopausal status, and race on the association of NAF hormones and breast cancer risk. We will seek corroborating evidence for the biological importance of NAF hormone levels by examining the NAF content of estrogen and progesterone related proteins. By examining the hormone receptor (HR) status of the cancers among cases, we will test the hypothesis that NAF hormone levels are more strongly related to HR positive breast cancers. Finally, we will assess the degree to which NAF hormones explain mammographic density in cases and controls. This project, evaluating breast intracrinology, mammographic density, and cancer risk will provide data on the validity of NAF hormones as new breast cancer risk markers, which can potentially be modulated by preventive interventions and therefore may serve as surrogate endpoints to assess their effects.

描述（由申请人提供）：终生暴露于性类固醇是乳腺癌风险的主要因素。如果有可能评估激素敏感乳腺癌的风险，则针对内分泌轴的预防策略的风险效益比将得到显着改善。乳液激素水平是乳腺癌风险的有吸引力的候选标志物。我们的试点研究提供了初步数据，即性类固醇水平（NAF）的性类固醇水平（雌二醇和孕酮）是绝经前和绝经后妇女乳腺癌风险的潜在生物标志物。我们表明，NAF的这些标记显着高于血清，随着时间的推移稳定，并且在生物学上具有相关性，正如NAF雌二醇水平与NAF中雌激素反应蛋白的含量的强相关性所反映的那样。此外，我们表明，NAF的激素含量反映了系统环境，因为激素水平随使用激素替代疗法而上升，口服避孕药使用者的含量较低，并且在停止口服避孕药后增加。最后，初步分析首次表明，NAF雌二醇和孕酮与估计的Gail风险之间的相关性。该提案中要研究的主要假设是NAF雌二醇水平是激素敏感乳腺癌的风险标志。为此，我们提出了一项对600名妇女的病例对照研究：300名新诊断为林恩·贤者乳房中心40至60岁的乳腺癌病例，以及来自西北地区邻近乳房X线摄影筛查中心的300例对照。案件和控件将与年龄和更年期状态相匹配。我们将获得NAF，血液样本和乳腺X线摄影密度测量。 NAF分析将包括性类固醇（雌二醇和孕激素），其前体（雌激素，硫酸雌酮，雄激素二羟基苯甲酸酯和睾丸激素）及其相关蛋白质（表皮生长因子，Catherpsin d，ps2，ps2，PS2，PS2，PS2，PS2和前列腺特异性抗原）。我们将执行亚分析，以检查特定的乳腺癌危险因素，绝经状态以及种族对NAF激素和乳腺癌风险关联的影响。我们将通过检查雌激素和孕酮相关蛋白的NAF含量来寻求证据证明NAF激素水平的生物学重要性。通过检查癌症在病例中的激素受体（HR）状态，我们将检验以下假设：NAF激素水平与HR阳性乳腺癌更密切相关。最后，我们将评估NAF激素在病例和对照中解释乳房X线摄影密度的程度。该项目评估乳房内部学，乳房X线照相密度和癌症风险将提供有关NAF激素作为新的乳腺癌风险标志物的有效性的数据，这些乳腺癌风险标志物可能受到预防干预措施的可能调节，因此可以作为评估其影响的替代终点。