Jennifer W. Wu, Laurent Azoulay, Jean-François Boivin, and Samy Suissa, McGill University; Jewish General Hospital; Michael Pollak, McGill University; and Agnieszka Majdan, Jewish General Hospital, Montreal, Quebec, Canada.
J Clin Oncol. 2017 Nov 10;35(32):3647-3653. doi: 10.1200/JCO.2017.73.4491. Epub 2017 Sep 27.
Purpose The association between long-acting insulin analogs and increased breast cancer risk is uncertain, particularly with the short follow-up in previous studies. We assessed this risk long term in women with type 2 diabetes. Methods A population-based cohort of women 40 years or older, all of whom were treated with long-acting (glargine, detemir) or neutral protamine Hagedorn (NPH) insulin between 2002 and 2012, was formed using the United Kingdom's Clinical Practice Research Datalink. Women were followed until February 2015 or breast cancer diagnosis. Cox proportional hazards models were used to estimate adjusted hazard ratios (HRs) and 95% CIs of incident breast cancer, comparing long-acting insulin analogs with NPH overall, as well as by duration and cumulative dose. Results The cohort included 22,395 women who received insulin treatment, with 321 incident breast cancer events occurring during up to 12 years of follow-up (incidence rate 3.3 per 1,000 person-years). Compared with NPH insulin, insulin glargine was associated with an increased risk of breast cancer (HR, 1.44; 95% CI, 1.11 to 1.85), mainly increasing 5 years after glargine initiation (HR, 2.23; 95% CI, 1.32 to 3.77) and after > 30 prescriptions (HR, 2.29; 95% CI, 1.26 to 4.16). The risk was particularly elevated among prior insulin users (HR, 1.53; 95% CI, 1.10 to 2.12) but not for new users, which included fewer patients and for which one cannot rule out an HR of 1.81. The risk associated with insulin detemir was not significantly elevated (HR, 1.17; 95% CI, 0.77 to 1.77). Conclusion Long-term use of insulin glargine is associated with an increased risk of breast cancer in women with type 2 diabetes. The risk associated with insulin detemir remains uncertain because there are fewer users of this insulin.
长效胰岛素类似物与乳腺癌风险增加之间的关联尚不确定，尤其是在之前的研究中随访时间较短。我们评估了 2 型糖尿病女性中这种风险的长期情况。
本研究通过英国临床实践研究数据链，建立了一个年龄在 40 岁或以上的人群队列，所有患者均在 2002 年至 2012 年期间接受长效（甘精胰岛素、地特胰岛素）或中性鱼精蛋白锌胰岛素（NPH）治疗。患者随访至 2015 年 2 月或乳腺癌确诊。采用 Cox 比例风险模型比较了长效胰岛素类似物与 NPH 总体以及根据持续时间和累积剂量的情况下，评估发生乳腺癌的校正风险比（HR）和 95%CI。
该队列包括 22395 名接受胰岛素治疗的女性，在 12 年的随访中发生了 321 例乳腺癌事件（发病率为每 1000 人年 3.3 例）。与 NPH 胰岛素相比，甘精胰岛素与乳腺癌风险增加相关（HR，1.44；95%CI，1.11 至 1.85），主要在甘精胰岛素开始使用后 5 年（HR，2.23；95%CI，1.32 至 3.77）和使用>30 剂后（HR，2.29；95%CI，1.26 至 4.16）增加。这种风险在先前使用胰岛素的患者中尤其升高（HR，1.53；95%CI，1.10 至 2.12），但对于新使用者则没有增加，新使用者的患者人数较少，不能排除 HR 为 1.81。与胰岛素地特胰岛素相关的风险没有显著增加（HR，1.17；95%CI，0.77 至 1.77）。
在 2 型糖尿病女性中，长期使用甘精胰岛素与乳腺癌风险增加相关。由于使用这种胰岛素的患者较少，因此与胰岛素地特胰岛素相关的风险仍不确定。
