Growth Hormones and Breast Cancer Risk

生长激素和乳腺癌风险

• 批准号: 8257494
• 负责人: Shelley S Tworoger
• 金额: $ 42.19万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-07-01 至 2014-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8257494
• 关键词: Address; Age; Age-Years; Androgens; Anti-Inflammatory Agents; Anti-inflammatory; Area; Biological Assay; Blood; Blood specimen; Body Size; Breast; Breast Cancer Model; Breast Cancer Risk Assessment Tool; Breast Cancer Risk Factor; Breast Feeding; Cancer Etiology; Cells; Chemoprevention; Clinical; Collection; Complex; Cyclin D1; Data; Development; Diagnosis; Epidemiologic Studies; Estrogen receptor positive; Estrogens; Etiology; Evaluation; First Births; Funding; Gonadal Steroid Hormones; Grant; Growth Factor; High Risk Woman; Hormones; Human; Immunoassay; Knowledge; Laboratory Animals; Lactation; Lead; Life; Lymphoma; Mammary Neoplasms; Mammographic Density; Mammography; Measurement; Measures; Melatonin; Menopause; Menstrual cycle; Modeling; Nurses' Health Study; Participant; Pathway interactions; Perimenopause; Pharmaceutical Preparations; Physical activity; Plasma; Population; Postmenopause; Premenopause; Prevention; Prolactin; Prolactin Receptor; Protein Isoforms; Questionnaires; Recording of previous events; Research; Risk; Risk Factors; Role; STAT3 gene; STAT5A gene; Sampling; Sleep; Somatotropin; Specificity; Staining method; Stains; Time; Tissue Microarray; Translating; Tumor Tissue; Vitamin D; Woman; Work; animal data; base; breast cancer diagnosis; cancer risk; carcinogenesis; case control; clinical practice; cohort; cost effective; cost effectiveness; design; follow-up; improved; malignant breast neoplasm; novel; parity; prospective; research study; shift work; tumor

ABSTRACT The relationship between growth factors and breast cancer etiology is complex and not completely understood; however, strong experimental evidence supports their role in breast carcinogenesis. Therefore, in this proposal, we will conduct a detailed evaluation of prolactin and its association with breast cancer risk. This study will use a prospective nested case-control design among pre- or perimenopausal women at blood collection (1,542 cases diagnosed through 2011). Samples were collected in the Nurses' Health Study II (NHSII) in 1996-99 from 29,611 women, ages 32 to 52 years, and in 1989-90 from 32,826 NHS participants, ages 43 to 62 years. In addition to assessing the overall prolactin-breast cancer association, this study will examine whether prolactin is more strongly associated with risk of estrogen receptor positive tumors, as well as tumors staining positive for prolactin, prolactin receptor, cyclin D1, and phosphorylated STAT3 and STAT5. Observing such specificity to the prolactin receptor and its downstream targets would add substantially to the case for causality. Prior studies have assessed prolactin levels using an immunoassay that measures multiple isoforms with differing biologic activities. This study will provide the first prospective assessment of breast cancer risk with a prolactin bioactivity assay, which may better reflect the portion of prolactin that is biologically important. Also, since few correlates of bioactive prolactin are known, this proposal will assess, for the first time, its relationship with known and putative breast cancer risk factors (e.g., parity, shift work). The availability of existing hormone data for this cohort will enable the examination of prolactin as an independent breast cancer risk factor and its interrelationships with other hormones. Importantly, we have added an aim to directly evaluate the addition of prolactin to a comprehensive risk prediction model for breast cancer, which could be useful clinically. Several features of prolactin make it an attractive candidate for inclusion into such models, including that the immunoassay is a standardized and common clinical assay that is very inexpensive and easy to measure. Further, the magnitude of the prolactin association appears to be similar to other factors included in breast cancer risk prediction models. We also will evaluate the inclusion of the bioassay; if this improves prediction better than the immunoassay, it would provide impetus to identify the specific isoforms of prolactin that increase risk of breast cancer and develop inexpensive assays for their measurement. Other grants will provide funding for follow-up and other hormone assays, increasing the cost-effectiveness of this project. Ultimately, elucidating the role of prolactin in breast cancer could open up multiple new areas of research for both treatment and prevention.

抽象的 生长因子与乳腺癌病因之间的关系很复杂，尚未完全理解。 但是，有力的实验证据支持它们在乳腺癌发生中的作用。因此，在此 提案，我们将对催乳素及其与乳腺癌风险的关联进行详细评估。这 研究将在血液前或围绝经内妇女中使用前瞻性嵌套的病例对照设计 收集（在2011年诊断为1,542例病例）。在护士健康研究II中收集样品II （NHSII）1996 - 99年，从29,611名女性，年龄在32至52岁之间，1989 - 90年从32,826 NHS参与者， 年龄43至62岁。除了评估整体催乳素 - 胸癌协会外，这项研究还将 检查催乳素是否与雌激素受体阳性肿瘤的风险更密切相关 作为催乳素，催乳素受体，细胞周期蛋白D1和磷酸化的STAT3和STAT5的肿瘤染色阳性。 观察对催乳素受体及其下游靶标的这种特异性将大大增加 因果关系的案例。先前的研究已使用用于测量多个的免疫测定法评估了催乳素水平 具有不同生物学活性的同工型。这项研究将对乳房进行首次前瞻性评估 催乳素生物活性测定法的癌症风险，可以更好地反映生物学上催乳素的一部分 重要的。同样，由于很少知道生物活性催乳素的相关性，因此该提案将评估第一个建议 时间，它与已知和推定的乳腺癌危险因素（例如，平等，转移工作）的关系。可用性 该队列的现有激素数据将使催乳素作为独立乳腺 癌症危险因素及其与其他激素的相互关系。重要的是，我们添加了直接的目标 评估将催乳素添加到乳腺癌的综合风险预测模型中，这可能是 在临床上有用。催乳素的几个特征使其成为将这种模型纳入此类模型的有吸引力的候选者 包括免疫测定是一种标准化且常见的临床测定法，非常便宜且容易 测量。此外，催乳素关联的大小似乎与包括其他因素相似 在乳腺癌风险预测模型中。我们还将评估生物测定的包含；如果这有所改善 预测比免疫测定更好，它将提供识别催乳素的特定同工型的动力 这增加了乳腺癌的风险并开发出廉价的测量方法以进行测量。其他赠款将 为随访和其他激素分析提供资金，从而提高了该项目的成本效益。 最终，阐明催乳素在乳腺癌中的作用可能会为多个新的研究领域开放 治疗和预防。