Department of Community Medicine and Epidemiology, Carmel Medical Center and Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology and Clalit National Cancer Control Center, Haifa, Israel.
Zuckerman STEM Post-Doctoral Fellowship Program, Zuckerman Institute, Tel Aviv, Israel.
Int J Epidemiol. 2022 Jun 13;51(3):807-816. doi: 10.1093/ije/dyac004.
Approximately one in six women in the USA takes antidepressants and a third use selective serotonin reuptake inhibitors (SSRIs) after breast cancer diagnosis. Recent investigation demonstrated serotonin receptor (5-HTR2B) expression in the breast and serotonin production as an indicator of poor breast cancer prognosis. This study investigates the association between SSRI use at different time intervals relative to breast cancer diagnosis on survival.
A population-based sample of 6959 consecutive, newly diagnosed breast cancer cases in Northern Israel was included. Patients were recruited from January 2000 and followed up through March 2020. Participants completed risk factor questionnaires regarding medical, reproductive and family history, medication use and health habits. Full prescription data were available through the Israeli national Clalit medical database. Multivariate Cox proportional hazard models were used to determine survival based on time of SSRI use.
Use of SSRIs in the 5 years prior to breast cancer diagnosis was associated with a 66% increase in overall mortality (HRadj = 1.66; CI: 1.05-2.63). SSRI use that initiated after breast cancer diagnosis was associated with an 81% increase in mortality (HRadj = 1.81; CI: 1.58-2.06). Use of SSRIs in the 5 years post-diagnosis was associated with a dose-response increase (P < 0.001) in long-term mortality (>5 years). Heavy SSRI use (≥24 prescription fills) after diagnosis was associated with nearly doubling in mortality (HR = 1.99; CI: 1.39-2.83).
SSRI use prior to and after breast cancer diagnosis is associated with increased mortality in breast cancer patients. Additional research is needed to better understand mechanisms mediating this association.
在美国，大约六分之一的女性在被诊断出患有乳腺癌后会服用抗抑郁药，其中三分之一会使用选择性 5-羟色胺再摄取抑制剂（SSRIs）。最近的研究表明，5-羟色胺受体（5-HTR2B）在乳房中表达，而 5-羟色胺的产生则是乳腺癌预后不良的一个指标。本研究旨在探讨乳腺癌诊断前后不同时间间隔使用 SSRIs 与生存的关系。
纳入了以色列北部一个由 6959 例连续新诊断乳腺癌患者组成的基于人群的样本。患者于 2000 年 1 月招募，并随访至 2020 年 3 月。参与者完成了有关医疗、生殖和家族史、用药和健康习惯的风险因素问卷。通过以色列全国医疗保健系统 Clalit 的数据库获得了完整的处方数据。使用多变量 Cox 比例风险模型根据 SSRI 使用时间确定生存情况。
在乳腺癌诊断前 5 年内使用 SSRIs 与总死亡率增加 66%相关（调整后的 HR = 1.66；95%CI：1.05-2.63）。在乳腺癌诊断后开始使用 SSRIs 与死亡率增加 81%相关（调整后的 HR = 1.81；95%CI：1.58-2.06）。在诊断后 5 年内使用 SSRIs 与长期死亡率（>5 年）呈剂量反应增加（P < 0.001）相关。在诊断后大量使用 SSRIs（≥24 张处方）与死亡率增加近两倍相关（HR = 1.99；95%CI：1.39-2.83）。
在乳腺癌诊断前后使用 SSRIs 与乳腺癌患者的死亡率增加相关。需要进一步研究以更好地理解介导这种关联的机制。
