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.

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.

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).

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，尤其是在先前研究中随访时间较短的情况下。我们对患有2型糖尿病的妇女的这一长期风险进行了评估。

根据英国的临床实践研究数据链，在40岁以上的人群中，均于2002年至2012年间接受了长效（长效谷氨酰胺，地特米尔）或中性鱼精蛋白Hagedorn（NPH）胰岛素治疗的人群。对女性进行随访直至2015年2月或诊断为乳腺癌。使用Cox比例风险模型来评估经过调整的风险比（HRs）和发生乳腺癌的95％CI，通过比较长效胰岛素类似物与NPH的总体，持续时间和累积剂量来比较。

该队列包括22395名接受胰岛素治疗的妇女，在长达12年的随访中发生了321起乳腺癌事件（每千人年3.3的发生率）。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），主要是在甘精胰岛素启动后5年内增加（HR，2.23； 95％CI，1.32至3.77）。并经过30次以上的处方后（HR，2.29； 95％CI，1.26至4.16）。在以前的胰岛素使用者中，该风险特别高（HR，1.53； 95％CI，1.10至2.12），但对于新使用者则不然，新使用者包括较少的患者，并且不能排除HR为1.81。与胰岛素地特米尔相关的风险没有显着升高（HR，1.17； 95％CI，0.77至1.77）。

长期使用甘精胰岛素会增加2型糖尿病女性患乳腺癌的风险。与胰岛素地特米尔有关的风险仍然不确定，因为这种胰岛素的使用者较少。