Department of Adult Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Breast Cancer Res Treat. 2012 Jan;131(2):589-97. doi: 10.1007/s10549-011-1754-1. Epub 2011 Sep 1.
Clinical trials suggest that increased risk of osteoporosis and fracture are the only serious side effects of adjuvant aromatase inhibitors (AIs), but little is known regarding toxicities of AIs in non-trial populations. We evaluated whether use of AIs was associated with myocardial infarction, stroke, and fracture in a community-based population. Using data from the HealthCore Integrated Research Database, 44,463 women aged ≥ 50 years with ≥ 2 breast cancer diagnosis codes between 2001 and 2007 were followed through 2008. Of these, 44,026 were matched using propensity score methods to women aged ≥ 50 years with no breast cancer codes. We assessed whether treatment with AIs was associated with myocardial infarction, stroke, and fracture using Cox proportional hazards models with time-varying treatment variables. Among breast cancer patients, 68.7% received no hormonal therapy, 20.6% received AIs (15.8% received only AIs, 4.8% were also treated with tamoxifen), and 10.7% received tamoxifen only. Breast cancer patients on AIs had a higher risk of any fracture (AHR = 1.13, 95% CI = 1.02-1.25) than breast cancer patients not receiving hormonal therapy. Patients on tamoxifen had a lower risk of hip fracture (AHR = 0.51, 95% CI = 0.32-0.81) than breast cancer patients not receiving hormonal therapy. Rates of myocardial infarction and stroke for patients on AIs or tamoxifen did not differ significantly from breast cancer patients not on therapy. The side effect profile of AIs in this community-based population was similar to that seen in clinical trials. These findings provide reassurance that AIs appear to be associated with few serious side effects.
临床试验表明，骨质疏松症和骨折风险增加是芳香化酶抑制剂（AIs）唯一的严重副作用，但对于非试验人群中 AIs 的毒性知之甚少。我们评估了在基于社区的人群中，使用 AIs 是否与心肌梗死、中风和骨折有关。使用 HealthCore 综合研究数据库的数据，我们对 2001 年至 2007 年间至少有 2 个乳腺癌诊断代码的年龄≥50 岁且≥44463 名女性进行了随访，直至 2008 年。其中，44026 名女性通过倾向评分方法与年龄≥50 岁且没有乳腺癌代码的女性进行了匹配。我们使用时变治疗变量的 Cox 比例风险模型评估了 AIs 的治疗是否与心肌梗死、中风和骨折有关。在乳腺癌患者中，68.7%未接受激素治疗，20.6%接受 AIs（15.8%仅接受 AIs，4.8%同时接受他莫昔芬治疗），10.7%仅接受他莫昔芬治疗。接受 AIs 治疗的乳腺癌患者发生任何骨折的风险更高（AHR=1.13，95%CI=1.02-1.25），而未接受激素治疗的乳腺癌患者。接受他莫昔芬治疗的患者髋部骨折的风险较低（AHR=0.51，95%CI=0.32-0.81），而未接受激素治疗的乳腺癌患者。接受 AIs 或他莫昔芬治疗的患者心肌梗死和中风的发生率与未接受治疗的乳腺癌患者无显著差异。在这个基于社区的人群中，AIs 的副作用谱与临床试验中观察到的相似。这些发现提供了保证，即 AIs 似乎与很少有严重副作用相关。
