The Role of Prolactin in Postmenopausal Breast Cancer

催乳素在绝经后乳腺癌中的作用

• 批准号: 6948505
• 负责人: FRANCESMARY MODUGNO
• 金额: $ 7.43万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-09-14 至 2007-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6948505
• 关键词: biomarker; breast neoplasms; cancer prevention; cancer risk; estrogen receptors; female; hormone therapy; human data; meta analysis; neoplasm /cancer epidemiology; postmenopause; progesterone receptors; prolactin; women' s health

DESCRIPTION (provided by applicant): Laboratory data suggests that prolactin (PRL), a hormone that controls breast development and lactation, may also play a role in breast carcinogenesis. Data in humans has been sparse consisting of mainly case-control studies with extremely small sample sizes. Only one large prospective study (the Nurses" Health Study) has examined the question, noting a significant positive association between plasma PRL levels similar in magnitude to that of estrogen and breast cancer. If validated, these findings would suggest additional areas for focused research into the development of chemopreventive agents, similar to the development of SERMS for breast cancer prevention. Thus, a large prospective study is urgently needed. The objective of this application is to prospectively evaluate the extent to which PRL levels are related to breast cancer in postmenopausal women. We will specifically test the following hypothesis: Among postmenopausal women, serum prolactin levels are positively associated with breast cancer risk. We will further evaluate the effects of sex steroid hormones and growth factors levels on the prolactin-breast cancer association. As a secondary aim, we will explore the relationship of prolactin levels to clinical characteristics of breast cancer, including tumor stage, grade and ER/PR status. We will undertake a case-cohort study within the Study of Osteoporotic Fractures (SOF). SOF is a prospective study that collected risk factor data and banked fasting serum on 9704 postmenopausal women in the United States. Since 1986, 481 women were diagnosed with breast cancer after enrollment. We will measure prolactin levels in the prospectively-collected serum of 375 women who developed breast cancer during follow-up and 375 SOF participants who did not develop the disease during follow-up. To assess the relationship between prolactin and breast cancer, we will use Cox regression models controlling for covariates such as age, family history, age at first birth, age at menarche, age at menopause, past use of hormone replacement therapy, parity, ever breast fed, and history of benign breast disease, as well as factors affecting prolactin. A positive finding in our study will support the development of breast cancer chemopreventive agents aimed at the prolactin pathway. Approval for this study has already been obtained from SOF and we can begin the study as soon as funding is obtained.

描述（由申请人提供）： 实验室数据表明，催乳素（PRL）是一种控制乳房发育和哺乳的激素，也可能在乳腺癌发生中发挥作用。人类数据很少，主要由样本量极小的病例对照研究组成。只有一项大型前瞻性研究（护士健康研究）探讨了这个问题，指出血浆 PRL 水平与雌激素水平相似，与乳腺癌之间存在显着的正相关关系。如果得到验证，这些发现将表明需要重点研究的其他领域化学预防剂的开发，类似于乳腺癌预防的 SERMS 的开发，因此，迫切需要进行一项大型前瞻性研究，旨在前瞻性评估 PRL 水平与乳腺癌的相关程度。我们将专门检验以下假设：在绝经后妇女中，血清催乳素水平与乳腺癌风险呈正相关。我们将进一步评估性类固醇激素和生长因子水平对催乳素与乳腺癌之间关系的影响。第二个目标是探讨催乳素水平与乳腺癌临床特征的关系，包括肿瘤分期、分级和 ER/PR 状态。我们将在骨质疏松性骨折研究 (SOF) 范围内进行病例队列研究。 SOF 是一项前瞻性研究，收集了美国 9704 名绝经后妇女的危险因素数据并储存了空腹血清。自1986年以来，有481名女性在入学后被诊断出患有乳腺癌。我们将测量前瞻性收集的 375 名在随访期间患乳腺癌的女性和 375 名在随访期间未患乳腺癌的 SOF 参与者血清中的催乳素水平。为了评估催乳素和乳腺癌之间的关系，我们将使用 Cox 回归模型控制协变量，例如年龄、家族史、第一次生育年龄、初潮年龄、绝经年龄、既往使用激素替代疗法、产次、曾经乳房喂养情况、良性乳腺疾病史，以及影响催乳素的因素。我们研究的积极发现将支持针对催乳素途径的乳腺癌化学预防剂的开发。这项研究已经获得SOF的批准，一旦获得资金我们就可以开始研究。