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）：终生接触性类固醇是乳腺癌风险的一个主要因素。如果能够评估激素敏感性乳腺癌的风险，那么针对内分泌轴的预防策略的风险效益比将显着提高。乳头液激素水平是乳腺癌风险的有吸引力的候选标志。我们的初步研究提供了初步数据，表明乳头抽吸液 (NAF) 中性类固醇（雌二醇和黄体酮）的水平是绝经前和绝经后女性患乳腺癌风险的潜在生物标志物。我们发现，这些标记物在 NAF 中显着高于在血清中，并且随着时间的推移保持稳定，并且具有生物学相关性，正如 NAF 雌二醇水平与 NAF 中雌激素反应蛋白含量的强相关性所反映的那样。此外，我们发现NAF的激素含量反映了全身环境，因为激素水平随着激素替代疗法的使用而升高，在口服避​​孕药使用者中较低，并且在停止口服避孕药后升高。最后，初步分析首次显示 NAF 雌二醇和黄体酮与估计的盖尔风险之间的相关性。该提案要检验的主要假设是 NAF 雌二醇水平是激素敏感乳腺癌风险的标志。为了实现这一目标，我们提议对 600 名女性进行病例对照研究：300 名来自 Lynn Sage 乳腺中心的 40 至 60 岁新诊断乳腺癌病例，以及来自邻近的西北大学乳房 X 光检查中心的 300 名对照患者。病例和对照将根据年龄和绝经状况进行匹配。我们将获得 NAF、血液样本和乳房 X 光密度测量值。 NAF 检测包括性类固醇（雌二醇和黄体酮）、其前体（雌酮、硫酸雌酮、雄烯二酮、脱氢表雄酮和睾酮）和相关蛋白质（表皮生长因子、组织蛋白酶 D、pS2 和前列腺特异性抗原）。我们将进行亚组分析，以检查特定乳腺癌风险因素、绝经状态和种族对 NAF 激素与乳腺癌风险之间关系的影响。我们将通过检查雌激素和孕激素相关蛋白的 NAF 含量，寻求 NAF 激素水平生物学重要性的确凿证据。通过检查病例中癌症的激素受体 (HR) 状态，我们将检验 NAF 激素水平与 HR 阳性乳腺癌密切相关的假设。最后，我们将评估 NAF 激素解释病例和对照乳房 X 光密度的程度。该项目评估乳腺分泌学、乳房 X 光密度和癌症风险，将提供 NAF 激素作为新的乳腺癌风险标记物有效性的数据，该标记物可以通过预防性干预措施进行调节，因此可以作为评估其效果的替代终点。