ABC: Antidepressants and Breast Cancer Pharmacoepidemiology

描述(申请人提供)：ABC：抗抑郁剂和乳腺癌治疗药物流行病学成千上万的美国乳腺癌患者正在服用他莫昔芬，以降低复发或第二次原发乳腺癌的机会。这些女性中的许多人还服用抗抑郁药。由于他莫昔芬的副作用会降低女性的生活质量和睡眠质量，包括潮热、盗汗和抑郁，而且荷尔蒙替代疗法是乳腺癌女性的禁忌，因此抗抑郁药物越来越多地被用于缓解他莫昔芬引起的症状。此外，大约50%的女性在确诊为乳腺癌后出现抑郁，通常会开出抗抑郁药。最近的证据表明，选择性5-羟色胺再摄取抑制剂(SSRI)抗抑郁药可能会将他莫昔芬的代谢降低到其活性形式，这可能会降低他莫昔芬对复发或第二次原发乳腺癌的保护作用。这种可能性需要调查。作为一些小规模研究的结果，最近的一些报告警告医生不要在他莫昔芬的同时开SSRI药物。然而，两项临床研究的结果是模棱两可的。只有一项小型研究报告了服用他莫昔芬的女性中抗抑郁药物与乳腺癌死亡率之间的关联，而另一项研究则没有发现关联。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情况。由于数以万计的女性可能同时服用他莫昔芬和抗抑郁药，因此确定SSRI是否真的降低了乳腺癌幸存者中他莫昔芬对继发乳腺癌的保护作用是至关重要的。该项目的目标是调查与只使用他莫昔芬治疗的类似女性相比，同时使用抗抑郁药物和他莫昔芬是否会增加被诊断为第一原发乳腺癌的女性继发乳腺癌(复发或第二原发癌)的风险。从一个服务于600多万会员的SEER附属电子肿瘤登记系统中，我们将汇集超过25,000名被诊断患有早期雌激素受体阳性乳腺癌并接受他莫昔芬治疗的妇女(其中约12,000人曾接触过抗抑郁药物)。使用健康计划的全面药房数据库，我们将确定哪些女性也接受了SSRI或其他抗抑郁药物的治疗。然后，我们将确定该队列中所有继发乳腺癌的女性和那些仍未患乳腺癌的女性，以确定SSRI或其他抗抑郁药的使用是否与继发乳腺癌的风险增加有关。最后，使用队列中的病例对照嵌套研究，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”(抗抑郁药与乳腺癌)研究提供了第一个真正的机会，来确定在最初患乳腺癌后同时服用他莫昔芬和抗抑郁药的妇女是否比没有服用SSRIs或其他抗抑郁药的暴露于他莫昔芬的妇女更有可能患上后续乳腺癌。 公共卫生相关性：这项研究将确定与只接触他莫昔芬的女性相比，联合使用抗抑郁药(包括SSRI或其他类型)和他莫昔芬是否会增加乳腺癌幸存者患乳腺癌的风险，从而对她们的健康构成严重威胁。由于抑郁和潮热在乳腺癌患者中都很常见，有关三苯氧胺和抗抑郁药联合使用的安全性或不良反应的信息将对治疗乳腺癌诊断后的抑郁和潮热具有深远的临床意义。如果没有发现关联，这将保证继续给被诊断为乳腺癌的女性开出某些抗抑郁药物。

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.