Type 2 Diabetes, but Not Insulin (Analog) Treatment, Is Associated With More Advanced Stages of Breast Cancer: A National Linkage of Cancer and Pharmacy Registries
Type 2 Diabetes, but Not Insulin (Analog) Treatment, Is Associated With More Advanced Stages of Breast Cancer: A National Linkage of Cancer and Pharmacy Registries
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DOI：
10.2337/dc18-2146
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发表时间：
2019-03-01
期刊：
影响因子：
16.2
通讯作者：
Nijpels, Giel
中科院分区：
文献类型：
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作者：
Overbeek, Jetty A.;van Herk-Sukel, Myrthe P. P.;Nijpels, Giel
目的研究2型糖尿病（T2 D）女性是否发展为更晚期的乳腺癌，以及胰岛素（类似物）治疗是否与特定的乳腺癌特征相关。研究设计和方法对于这项巢式病例对照研究，2002-2014年诊断为乳腺癌的女性选自荷兰癌症登记-PHARMO数据库网络（N = 33，377）。T2 D定义为在乳腺癌诊断前接受两次或多次非胰岛素降糖药物治疗。患有T2 D的女性与没有糖尿病的女性相匹配。在患有T2 D的女性中，比较了胰岛素使用者和非使用者。采用多变量有序Logistic回归分析T2 D/胰岛素与乳腺癌特征之间的关系，包括TNM分类（肿瘤大小、淋巴结状态、转移）、形态学、分级、雌激素受体和孕激素受体（PR）、人表皮生长因子受体2和分子亚型。结果与非糖尿病女性（n = 6，267）相比，T2 D女性（n = 1，567）更常被诊断为更晚期的肿瘤分期（比值比1.28 [95%CI 13-1.44]）和更高的级别（1.22 [1.08-1.39]），尽管PR阴性乳腺肿瘤（0.77 [0.67-0.89]）的频率较低。未发现与其他乳腺癌特征相关。与未使用胰岛素的T2 D女性（n = 1，179）相比，使用胰岛素的T2 D女性（n = 388）未被诊断为不同的乳腺癌特征。结论：我们的研究表明，与无糖尿病的女性相比，患有T2 D的女性被诊断为更具侵袭性的乳腺癌的风险增加。没有证据表明使用胰岛素（类似物）与发展更晚期的乳腺癌肿瘤有关。
OBJECTIVE To investigate whether women with type 2 diabetes (T2D) develop a more advanced stage of breast cancer and whether treatment with insulin (analogs) is associated with specific breast cancer characteristics. RESEARCH DESIGN AND METHODS For this nested case-control study, women with breast cancer diagnosed in 2002-2014 were selected from the linked Netherlands Cancer Registry-PHARMO Database Network (N = 33,377). T2D was defined as receiving two or more dispensings of noninsulin blood glucose-lowering drugs prior to breast cancer diagnosis. Women with T2D were matched to women without diabetes. Among women with T2D, insulin users and nonusers were compared. Multivariable ordinal logistic regression was used to investigate the association between T2D/insulin and breast cancer characteristics, including TNM classification (tumor size, lymph node status, metastasis), morphology, grade, estrogen receptor and progesterone receptor (PR), human epidermal growth factor receptor 2, and molecular subtype. RESULTS Women with T2D (n = 1,567) were more often diagnosed with a more advanced tumor stage (odds ratio 1.28 [95% CI 13-1.44]) and a higher grade (1.22 [1.08-1.39]) though less often with a PR-negative breast tumor (0.77 [0.67-0.89]) than women without diabetes (n = 6,267). No associations were found for the other breast cancer characteristics. Women with T2D using insulin (n = 388) were not diagnosed with different breast cancer characteristics compared with women with T2D not using insulin (n = 1,179). CONCLUSIONS Our study suggests that women with T2D are at increased risk to be diagnosed with a more aggressive type of breast cancer than women without diabetes. No evidence was found that the use of insulin (analogs) is associated with developing more advanced breast cancer tumors.