Department of Community Health and Epidemiology, Carruthers Hall, Queen's University Kingston, ON, Canada.
Front Oncol. 2012 Dec 5;2:177. doi: 10.3389/fonc.2012.00177. eCollection 2012.
Selective serotonin reuptake inhibitors (SSRIs) are a widely prescribed class of antidepressants. Laboratory and epidemiologic evidence suggests that a prolactin-mediated mechanism secondary to increased serotonin levels at neuronal synapses could lead to a potentially carcinogenic effect of SSRIs. In this population-based case-control study, we evaluated the association between SSRI use and breast cancer risk as a function of their relative degree of inhibition of serotonin reuptake as a proxy for their impact on prolactin levels. Cases were 2,129 women with primary invasive breast cancer diagnosed from 2003 to 2007, and controls were 21,297 women randomly selected from the population registry. Detailed information for each SSRI prescription dispensed was compiled using the Saskatchewan prescription database. Logistic regression was used to evaluate the impact of use of high and lower inhibitors of serotonin reuptake and duration of use, as well as to assess the effect of individual high inhibitors on the risk of breast cancer. Exclusive users of high or lower inhibitors of serotonin reuptake were not at increased risk for breast cancer compared with non-users of SSRIs (OR = 1.01, CI = 0.88-1.17 and OR = 0.91, CI = 0.67-1.25 respectively), regardless of their duration of use or menopausal status. While we cannot rule out the possibility of a clinically important risk increase (OR = 1.83, CI = 0.99-3.40) for long-term users of sertraline (≥24 prescriptions), given the small number of exposed cases (n = 12), the borderline statistical significance, and the wide confidence interval, these results need to be interpreted cautiously. In this large population-based case-control study, we found no conclusive evidence of breast cancer risk associated with the use of SSRIs even after assessing the degree of serotonin reuptake inhibition and duration of use. Our results do not support the serotonin-mediated pathway for the prolactin-breast cancer hypothesis.
选择性 5-羟色胺再摄取抑制剂（SSRIs）是一类广泛应用的抗抑郁药。实验室和流行病学证据表明，神经元突触中血清素水平升高导致的催乳素介导机制可能导致 SSRIs 具有潜在致癌作用。在这项基于人群的病例对照研究中，我们评估了 SSRIs 使用与乳腺癌风险之间的关联，其作用机制是通过 SSRIs 对血清素再摄取的抑制程度（作为其对催乳素水平影响的替代指标）来评估。病例组为 2003 年至 2007 年间诊断出的 2129 名原发性浸润性乳腺癌女性，对照组为从人群登记处随机抽取的 21297 名女性。使用萨斯喀彻温省处方数据库详细编制了每位患者 SSRIs 处方的使用信息。使用逻辑回归评估了高和低血清素再摄取抑制剂的使用、使用时间以及个体高抑制剂的使用对乳腺癌风险的影响。与未使用 SSRIs 的患者相比，高或低血清素再摄取抑制剂的独家使用者罹患乳腺癌的风险并未增加（比值比（OR）=1.01，95%置信区间（CI）=0.88-1.17 和 OR=0.91，95%CI=0.67-1.25），无论其使用时间或绝经状态如何。虽然我们不能排除长期使用舍曲林（≥24 剂）的患者（n=12）乳腺癌风险增加的可能性（OR=1.83，95%CI=0.99-3.40），但鉴于暴露病例数量较少（n=12）、统计意义边缘性和置信区间较宽，这些结果需要谨慎解释。在这项大型基于人群的病例对照研究中，我们甚至在评估了血清素再摄取抑制程度和使用时间后，没有发现与 SSRIs 使用相关的乳腺癌风险的确凿证据。我们的结果不支持催乳素-乳腺癌假说中的血清素介导途径。
