Growth Hormones and Breast Cancer Risk

生长激素和乳腺癌风险

• 批准号: 8089411
• 负责人: Shelley S Tworoger
• 金额: $ 43.58万
• 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/8089411
• 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; public health relevance; research study; shift work; tumor

DESCRIPTION (provided by applicant): 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. PUBLIC HEALTH RELEVANCE: The relationship between growth factors and breast cancer etiology is complex and not completely understood; this proposal will extend knowledge about how prolactin, an important growth hormone, is associated with breast cancer risk among premenopausal and perimenopausal women. Characterizing this relationship will provide important knowledge that will translate to prevention and treatment applications. In particular, evaluation of whether prolactin improves risk prediction models could lead to better assessment of women at high risk of breast cancer and more accurate targeting of chemoprevention to these women, given that the Gail model already is utilized clinically and prolactin is an easily measured hormone that is stable across the menstrual cycle and the menopausal transition.

描述（由申请人提供）：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，在此提案中，我们将对催乳素及其与乳腺癌风险的关联进行详细评估。这项研究将在收集血液中使用前期或绝经性妇女中的前瞻性病例对照设计（1,542例诊断为2011年）。 1996 - 99年在护士健康研究II（NHSII）中收集了样本，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，年龄在43至62岁之间。除了评估整体催乳素 - 胸癌的关联外，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以及催乳素受体，细胞周期蛋白D1和磷酸化的STAT3和STAT3和STAT5呈阳性的肿瘤是否更加密切相关。观察到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。先前的研究已经使用免疫测定法评估了催乳素水平，该免疫测定测量具有不同生物学活性的多种同工型。这项研究将通过催乳素生物活性测定法提供首次对乳腺癌风险的前瞻性评估，这可以更好地反映生物学上重要的催乳素的一部分。同样，由于很少知道生物活性催乳素的相关性，因此该提案将首次评估其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。现有的激素数据在该队列中的可用性将使催乳素作为独立的乳腺癌危险因素及其与其他激素的相互关系的研究。重要的是，我们添加了一个目的，目的是直接评估催乳素在乳腺癌的综合风险预测模型中的添加，这在临床上可能很有用。催乳素的几个特征使其成为将其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，非常便宜且易于测量。此外，催乳素关联的大小似乎与乳腺癌风险预测模型中包括的其他因素相似。我们还将评估生物测定的包含；如果这比免疫测定更好地改善了预测，它将提供动力，以识别催乳素的特定同工型，从而增加乳腺癌的风险并开发廉价的测量方法。其他赠款将为随访和其他激素分析提供资金，从而提高该项目的成本效益。最终，阐明催乳素在乳腺癌中的作用可能会为治疗和预防开辟多个新的研究领域。 公共卫生相关性：生长因素与乳腺癌病因之间的关系很复杂，尚未完全理解；该提案将扩展有关催乳素是一种重要的生长激素与绝经前和绝经次苏联妇女中乳腺癌风险有关的知识。表征这种关系将提供重要的知识，这些知识将转化为预防和治疗应用。特别是，鉴于癌症模型已经在临床上被利用，并且催乳素是一种易于测量的激素，因此评估催乳素是否改善风险预测模型是否可以更好地评估乳腺癌高风险的女性，并更准确地将化学预防靶向对这些女性进行靶向。