ABC: Antidepressants and Breast Cancer Pharmacoepidemiology

描述（由申请人提供）：ABC：抗抑郁药和乳腺癌治疗药物流行病学 成千上万的美国乳腺癌妇女正在服用他莫昔芬，以减少复发或第二原发性乳腺癌的机会。这些妇女中的许多人也服用抗抑郁药。由于他莫昔芬具有降低女性生活质量和睡眠质量的副作用，包括潮热，盗汗和抑郁症，并且由于激素替代疗法禁忌用于患有乳腺癌的女性，因此抗抑郁药越来越多地用于缓解由他莫昔芬引起的症状。此外，抗抑郁药通常用于大约50%的女性在乳腺癌诊断后经历抑郁症。最近的证据表明，选择性5-羟色胺再摄取抑制剂（SSRI）抗抑郁药可能会降低他莫昔芬的代谢，使其成为活性形式，这可能会降低他莫昔芬对复发性或第二原发性乳腺癌的保护作用。这种可能性需要调查。由于一些小的研究，最近的一些报告警告医生不要同时开SSRI药物和他莫昔芬。然而，两项临床研究的结果并不明确。只有一项小型研究报告了服用他莫昔芬的女性抗抑郁药与乳腺癌死亡率之间的关联，而另一项研究则没有发现任何关联。重要的是，到目前为止，还没有研究充分衡量抗抑郁药的使用。由于成千上万的女性可能同时服用他莫昔芬和抗抑郁药，因此确定SSRIs是否确实降低了他莫昔芬对乳腺癌幸存者随后患乳腺癌的保护作用至关重要。该项目的目的是调查与仅用他莫昔芬治疗的类似女性相比，在已被诊断患有第一原发性乳腺癌的女性中，同时使用抗抑郁药和他莫昔芬是否会增加后续乳腺癌（复发或第二原发性肿瘤）的风险。从SEER附属的电子肿瘤登记处服务超过600万会员，我们将收集一个大型队列超过25,000名妇女诊断为第一个早期雌激素受体阳性乳腺癌和治疗与他莫昔芬（其中约12,000人暴露于抗抑郁药）。使用健康计划的综合药房数据库，我们将确定哪些妇女也用SSRI或其他抗抑郁药治疗。然后，我们将确定所有随后发生乳腺癌的妇女和在该队列中保持无乳腺癌的妇女，以确定SSRIs或其他抗抑郁药的使用是否与随后乳腺癌的风险增加有关。最后，在队列中使用病例对照嵌套研究，我们将确定某些因素是否混淆或改变了这种关联。这项创新的“ABC”（抗抑郁药和乳腺癌）研究提供了第一个真实的机会，以确定在最初的乳腺癌后同时服用他莫昔芬和抗抑郁药的女性是否比暴露于他莫昔芬但不服用SSRI或其他抗抑郁药的女性更有可能发展为后续乳腺癌。 公共卫生相关性： 这项研究将确定与仅暴露于他莫昔芬的女性相比，抗抑郁药（包括SSRIs或其他类型）和他莫昔芬的联合使用是否会通过增加随后的乳腺癌风险而对乳腺癌幸存者构成严重的健康威胁。由于抑郁症和潮热在乳腺癌患者中很常见，关于他莫昔芬和抗抑郁药联合使用的安全性或不良反应的信息将在治疗乳腺癌诊断后的抑郁症和潮热方面具有深远的临床意义。如果没有发现相关性，这将为继续为诊断为乳腺癌的女性开某些抗抑郁药物提供保证。

DESCRIPTION (provided by applicant): ABC: Antidepressants & Breast Cancer Treatment Pharmacoepidemiology Tens of thousands of American women with breast cancer are taking tamoxifen to reduce their chances of developing a recurrence or second primary breast cancer. Many of these women also take antidepressants. Because tamoxifen has side effects that diminish a woman's quality of life and quality of sleep including hot flashes, night sweats, and depression, and because hormone replacement therapy is contraindicated for women with breast cancer, antidepressants increasingly have been used to relieve symptoms caused by tamoxifen. In addition, antidepressants are commonly prescribed for approximately 50% of women experiencing depression subsequent to a breast cancer diagnosis. Recent evidence suggests selective serotonin reuptake inhibitor (SSRI) antidepressants may reduce the metabolism of tamoxifen to its active form, which could reduce tamoxifen's protection against recurrent or a second primary breast cancer. This possibility needs investigation. As result of a few small studies, some recent reports caution physicians against prescribing SSRI medications concurrently with tamoxifen. However, findings from two clinical studies are ambiguous. Only one small study reported an association between antidepressants and breast cancer mortality in women taking tamoxifen while another found no association. Importantly, to date no study has adequately measured antidepressant use. Because tens of thousands of women are likely taking both tamoxifen and antidepressants, it is critical to determine if SSRIs indeed decrease the protection of tamoxifen against subsequent breast cancer among breast cancer survivors. The goal of this project is to investigate whether concomitant use of antidepressants and tamoxifen increases the risk of subsequent breast cancer (recurrence or second primary tumor) among women who have been diagnosed with a first primary breast cancer, compared to similar women treated only with tamoxifen. From a SEER-affiliated electronic tumor registry serving over 6 million members, we will assemble a large cohort of over 25,000 women diagnosed with a first early stage estrogen receptor positive breast cancer and treated with tamoxifen (of whom approximately 12,000 were exposed to antidepressants). Using a health plan's comprehensive pharmacy database, we will determine which women were also treated with SSRI or other antidepressants. We will then identify all women who developed a subsequent breast cancer and those who remained breast-cancer free in this cohort to determine if SSRIs or other antidepressant use is associated with an increased risk of subsequent breast cancer. Finally, using a case-control nested study within the cohort, we will determine if certain factors confound or modify the association. This innovative "ABC" (Antidepressants & Breast Cancer) study presents the first real opportunity to determine if women who take both tamoxifen and antidepressants following their initial breast cancer have a greater likelihood of developing subsequent breast cancer than women exposed to tamoxifen who do not take SSRIs or other antidepressants. PUBLIC HEALTH RELEVANCE: This study will determine if combined use of antidepressants (including SSRIs or other types) and tamoxifen poses serious health threats among breast cancer survivors by elevating subsequent breast cancer risks, compared to women who were only exposed to tamoxifen. As both depression and hot flashes are common in breast cancer patients, information about the safety or the adverse effects of combined tamoxifen and antidepressant use would have far reaching clinical implications in treating the depression and hot flashes after a diagnosis of breast cancer. If an association is not found, this would provide reassurance to continue prescribing certain antidepressant medications to women diagnosed with breast cancer.