ABC: Antidepressants and Breast Cancer Pharmacoepidemiology

ABC：抗抑郁药和乳腺癌药物流行病学

• 批准号: 8059706
• 负责人: Reina Haque
• 金额: $ 56.05万
• 依托单位: KAISER FOUNDATION RESEARCH INSTITUTE
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-04-15 至 2013-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8059706
• 关键词: Address; Adjuvant; Adverse effects; American; Antidepressive Agents; Antihypertensive Agents; Atypical hyperplasia; Body mass index; Breast; Breast Cancer Treatment; California; Cancer Patient; Cancer Survivor; Characteristics; Clinical; Clinical Research; Comorbidity; Comprehensive Health Planning; Cytochrome P-450 CYP2D6; Cytochrome P450; Data; Databases; Diagnosis; Diagnostic; Disease; Drug Interactions; Effectiveness; Electronics; Endogenous depression; Enzymes; Estrogen receptor positive; Ethnic Origin; Family; Family history of; First Degree Relative; Goals; Guidelines; Health; Health Maintenance Organizations; Health Planning; Hormone replacement therapy; Hot flushes; Investigation; Journals; Label; Life; Link; Manufacturer Name; Marketing; Measures; Medical; Menopause; Mental Depression; Metabolism; Molecular; Nested Case-Control Study; Night Sweating; Outcome; Paroxetine; Patients; Pharmaceutical Preparations; Pharmacoepidemiology; Pharmacologic Substance; Pharmacy facility; Physicians; Positioning Attribute; Primary Neoplasm; Publications; Quality of life; Race; Recording of previous events; Recurrence; Reporting; Risk; Safety; Selective Serotonin Reuptake Inhibitor; Sleep; Staging; Stroke; Symptoms; System; Tamoxifen; Time; Vasomotor; Venous Thrombosis; Woman; Women' s Group; breast cancer diagnosis; cancer recurrence; cancer risk; cohort; depressive symptoms; electronic data; evidence base; experience; health care service utilization; inhibitor/antagonist; innovation; lifestyle factors; malignant breast neoplasm; member; mortality; prevent; public health priorities; public health relevance; success; tumor; tumor registry

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.

描述（由申请人提供）：ABC：抗抑郁药与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来减少复发或第二原发性乳腺癌的机会。其中许多女性还服用抗抑郁药。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，而且由于激素替代疗法是乳腺癌女性的禁忌，抗抑郁药越来越多地被用于缓解他莫昔芬引起的症状。此外，大约50%的乳腺癌诊断后出现抑郁症的女性通常会服用抗抑郁药。最近的证据表明，选择性5 -羟色胺再摄取抑制剂（SSRI）抗抑郁药可能会降低他莫昔芬的活性代谢，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。由于一些小型研究的结果，最近的一些报告警告医生不要同时开SSRI类药物和他莫西芬。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服用抗抑郁药和乳腺癌死亡率之间的联系，而另一项研究则没有发现这种联系。重要的是，迄今为止还没有研究充分衡量抗抑郁药的使用情况。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后续乳腺癌的保护作用至关重要。该项目的目的是调查在诊断为原发性乳腺癌的妇女中，与仅接受他莫昔芬治疗的类似妇女相比，同时使用抗抑郁药和他莫昔芬是否会增加随后乳腺癌（复发或第二原发肿瘤）的风险。从seer附属的电子肿瘤登记处服务超过600万会员，我们将收集超过25,000名诊断为第一个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接受了SSRI或其他抗抑郁药的治疗。然后，我们将在这个队列中确定所有后来患乳腺癌的妇女和那些没有患乳腺癌的妇女，以确定SSRIs或其他抗抑郁药的使用是否与后来患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”（抗抑郁药与乳腺癌）研究首次提供了真正的机会，以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服用他莫昔芬但不服用SSRIs或其他抗抑郁药的妇女更有可能患后续乳腺癌。