Depression, Antidepressant Use, and Breast Cancer Risk

抑郁症、抗抑郁药的使用和乳腺癌风险

• 批准号: 8704461
• 负责人: Katherine Whitney Reeves
• 金额: $ 9.18万
• 依托单位: UNIVERSITY OF MASSACHUSETTS AMHERST
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-04-03 至 2016-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8704461
• 关键词: Address; Adult; Affect; Anti-Inflammatory Agents; Anti-inflammatory; Antidepressive Agents; Area; Attenuated; Benefits and Risks; Breast Cancer Risk Factor; Breast Carcinogenesis; Cohort Studies; Complex; Data; Depressed mood; Foundations; General Population; High Risk Woman; Hormone Receptor; Immune system; Inflammation; Joints; Link; Literature; Measurement; Mental Depression; Nurses' Health Study; Obesity; Participant; Patients; Population; Postmenopause; Premenopause; Prolactin; Prospective Studies; Public Health; Recording of previous events; Reporting; Research; Resources; Risk; Sampling; Selective Serotonin Reuptake Inhibitor; Time; Weighing patient; Woman; cancer risk; cost; experience; follow-up; knowledge base; malignant breast neoplasm; middle age; population based; prospective; public health relevance

DESCRIPTION (provided by applicant): Depression has been hypothesized to increase breast cancer risk, with a few prospective studies with e10 years of follow-up suggesting a 2-4 times increased breast cancer risk among women with depression. Antidepressants (ADs) might mitigate hypothesized influences of depression on breast cancer risk through anti-inflammatory effects or may increase breast cancer risk through increasing circulating prolactin, especially for selective serotonin reuptake inhibitors (SSRIs). However, the proportion of SSRI users in the general population who will experience increased prolactin is unknown, and literature relating ADs to breast cancer risk provide inconsistent results. Surprisingly, previous studies have not jointly considered depression and AD use; prior studies of depression on breast cancer risk have not controlled for AD use, and vice versa. Additionally, the possibility that any increased risk associated with AD use might be due to the depression for which the AD is prescribed rather than the AD itself has not been fully explored. Additional questions regarding the impact of duration of each of these factors on breast cancer risk also remain. As a result, the relationships between depression, AD use and breast carcinogenesis remain poorly understood. Clarifying both the independent and joint effects of these exposures will provide critical information for the millions of women who are depressed and/or use ADs. We propose a prospective cohort study using data from the Nurses' Health Study (NHS) and NHS2 with the objective of investigating the complex associations potentially linking depression, AD use, and prolactin to breast cancer risk. Data on depression and AD use, as well as a range of known breast cancer risk factors, are available from 93,696 women (with 3,952 incident breast cancers) in NHS starting in 2000 and from 103,825 women in NHS2 (with 3,571 incident breast cancers) starting in 1993. Additionally, a subset of NHS and NHS2 participants (N=3,575 in NHS and N=1,549 in NHS2) have at least one prolactin measurement available for analysis. This unique resource will afford us excellent statistical power and substantial efficiencies in cos and time to address the following Specific Aims: 1. To evaluate whether depression increases risk of incident breast cancer independent of AD use; 2. To assess the effects of AD use on incident breast cancer risk; and 3. To determine the effects of AD use on circulating prolactin levels. This will be the first study to comprehensively evaluate the relationships between depression, AD use and breast cancer and to examine the effects of ADs on circulating prolactin levels in a large, population-based sample. This research will provide vital new information for clinicians and patients considering the risks and benefits of treatment for depression. Our results can fill key gaps in the knowledge base while providing the foundation for further study (e.g. relating changes in prolactin levels resulting from SSRI use to incident breast cancer).

描述（由申请人提供）：人们假设抑郁症会增加患乳腺癌的风险，一些经过 10 年随访的前瞻性研究表明，患有抑郁症的女性患乳腺癌的风险会增加 2-4 倍。抗抑郁药（AD）可能通过抗炎作用减轻抑郁症对乳腺癌风险的假设影响，或者可能通过增加循环催乳素来增加乳腺癌风险，特别是对于 选择性血清素再摄取抑制剂（SSRI）。然而，一般人群中 SSRI 使用者中催乳素升高的比例尚不清楚，并且将 AD 与乳腺癌风险相关的文献提供了不一致的结果。令人惊讶的是，之前的研究并没有联合考虑抑郁症和 AD 的使用；先前关于抑郁症与乳腺癌风险的研究并未控制 AD 的使用，反之亦然。此外，与 AD 使用相关的任何增加的风险可能是由于 AD 所治疗的抑郁症而不是 AD 本身引起的，这一可能性尚未得到充分探讨。关于这些因素的持续时间对乳腺癌风险的影响的其他问题仍然存在。因此，人们对抑郁症、AD 使用和乳腺癌发生之间的关系仍知之甚少。澄清这些暴露的独立影响和联合影响将为数百万患有抑郁症和/或使用 AD 的女性提供重要信息。我们利用护士健康研究 (NHS) 和 NHS2 的数据提出一项前瞻性队列研究，目的是调查抑郁症、AD 使用和催乳素与乳腺癌风险之间潜在联系的复杂关联。有关抑郁症和 AD 使用情况以及一系列已知乳腺癌危险因素的数据可从 2000 年开始 NHS 中的 93,696 名女性（其中有 3,952 例乳腺癌发生）和自 2000 年开始 NHS2 中的 103,825 名女性（其中有 3,571 例发生乳腺癌）获得。 1993 年。此外，NHS 和 NHS2 参与者的子集（NHS 和 NHS2 中的 N=3,575 人） NHS2 中的 N=1,549）至少有一项催乳素测量可用于分析。这一独特的资源将为我们提供出色的统计能力和显着的成本和时间效率，以实现以下具体目标： 1. 评估抑郁症是否会增加乳腺癌发病风险，与 AD 的使用无关； 2. 评估 AD 使用对乳腺癌风险的影响； 3. 确定 AD 使用对循环催乳素水平的影响。这将是第一项全面评估抑郁症、AD 使用和乳腺癌之间关系的研究，并在大型人群样本中检查 AD 对循环催乳素水平的影响。这项研究将为临床医生和患者考虑抑郁症治疗的风险和益处提供重要的新信息。我们的结果可以填补知识库中的关键空白，同时为进一步研究提供基础（例如，将使用 SSRI 引起的催乳素水平变化与乳腺癌发生联系起来）。