The Role of Prolactin in Postmenopausal Breast Cancer

描述（由申请人提供）： 实验室数据表明，催乳素（PRL），一种控制乳房发育和泌乳的激素，也可能在乳腺癌发生中发挥作用。人类的数据很少，主要是病例对照研究，样本量极小。只有一项大型前瞻性研究（护士健康研究）研究了这个问题，指出血浆PRL水平与雌激素水平相似，与乳腺癌之间存在显著的正相关。如果得到验证，这些发现将为化学预防剂的开发提供更多的重点研究领域，类似于SERMS用于预防乳腺癌的开发。因此，迫切需要进行大规模的前瞻性研究。本申请的目的是前瞻性地评估PRL水平与绝经后妇女乳腺癌相关的程度。我们将特别检验以下假设：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相关性的影响。作为次要目的，我们将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）中进行一项病例队列研究。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和空腹血清。自1986年以来，481名妇女在登记后被诊断患有乳腺癌。我们将测量375名在随访期间患乳腺癌的妇女和375名在随访期间未患乳腺癌的SOF参与者的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，我们将使用考克斯回归模型控制协变量，如年龄、家族史、首次生育年龄、初潮年龄、绝经年龄、既往激素替代治疗的使用、产次、母乳喂养史和良性乳腺疾病史，以及影响催乳素的因素。在我们的研究中的一个积极的发现将支持乳腺癌化学预防剂的发展，旨在催乳素途径。这项研究已经获得了SOF的批准，一旦获得资金，我们就可以开始这项研究。

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.