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哺乳的激素，也可能在乳腺癌的发生中发挥作用。人类的数据一直很稀少，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)研究了这个问题，指出血浆催乳素水平与雌激素水平和乳腺癌之间存在显著的正相关关系。如果得到证实，这些发现将建议对化学预防药物的开发进行更多重点研究，类似于用于乳腺癌预防的SERMS的开发。因此，迫切需要一项大规模的前瞻性研究。这项应用的目的是前瞻性地评估绝经后妇女PRL水平与乳腺癌的关系程度。我们将具体检验以下假设：在绝经后女性中，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-乳腺癌相关性的影响。作为第二个目标，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(SOF)研究中进行一项病例队列研究。SOF是一项前瞻性研究，收集了危险因素数据并储存了9704名美国绝经后妇女的空腹血清。自1986年以来，有481名妇女在登记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参与者的血清中催乳素的水平。为了评估催乳素与乳腺癌的关系，我们将使用COX回归模型控制协变量，如年龄、家族史、首次生育年龄、月经初潮年龄、绝经年龄、既往使用激素替代疗法、产次、是否曾哺乳、良性乳腺疾病病史，以及影响催乳素的因素。我们研究中的一项积极发现将支持针对催乳素途径的乳腺癌化学预防药物的开发。这项研究的批准已经从SOF获得，一旦获得资金，我们就可以开始研究。

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.