Relationship between Diabetes and Diabetes Medications and Risk of Different Molecular Subtypes of Breast Cancer
Relationship between Diabetes and Diabetes Medications and Risk of Different Molecular Subtypes of Breast Cancer
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DOI：
10.1158/1055-9965.epi-19-0291
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发表时间：
2019-11-01
影响因子：
3.8
通讯作者：
Li, Christopher, I
中科院分区：
文献类型：
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作者：
Chen, Hongjie;Cook, Linda S.;Li, Christopher, I
背景：II型糖尿病和某些糖尿病治疗已被观察到影响乳腺癌的风险。然而，它们与由雌激素受体（ER）/孕激素受体（PR）/HER 2状态定义的不同乳腺癌分子亚型的关联尚不清楚。我们进行了一项回顾性多中心基于人群的病例-病例研究，包括4，557例乳腺癌病例，以评估II型糖尿病和糖尿病药物对不同乳腺癌分子亚型[ER+/HER 2（-），ER+/HER 2（+）、三阴性（ER-/PR-/HER 2（-））和HER 2过表达（H2 E，ER-/dPR（-）/HER 2（+））]。以ER+/HER 2（-）病例为参照组，采用多分类Logistic回归分析，估计各亚型的OR值及相应的95%可信区间（CI）。结果：与无糖尿病史的女性相比，II型糖尿病女性发生三阴性乳腺癌（TNBC）的几率增加38%（95%CI，1.01-1.89）。当前和近期长期使用二甲双胍（在乳腺癌诊断前的24个月内治疗13-24个月）与TNBC的几率升高相关。（OR = 1.54; 95%CI，1.07-2.22和OR = 1.80; 95%CI，1.13-2.85）。对于患有II型糖尿病的女性，特别是那些使用二甲双胍的女性，患三阴性而不是ER+/HER 2（-）乳腺癌的几率更大。这一发现得到了一些临床前数据的支持，表明糖尿病可能与三阴性疾病的风险更密切相关。影响：我们的研究提供了新的证据，关于II型糖尿病和二甲双胍使用对不同分子亚型乳腺癌风险的潜在差异效应。
Background: Type II diabetes and certain diabetes treatments have been observed to impact breast cancer risk. However, their associations with different breast cancer molecular subtype defined by estrogen receptor (ER)/progesterone receptor (PR)/HER2 status are unclear.Methods: We conducted a retrospective multi-center population-based case-case study consisting of 4,557 breast cancer cases to evaluate the impact of type II diabetes and diabetes medications on the risk of different breast cancer molecular subtypes [ER+/HER2(-), ER+/HER2(+), triple negative (ER-/PR-/HER2(-)), and HER2 overexpressing (H2E, ER-/dPR(-)/HER2(+))]. Using ER+/HER2(-) cases as the reference group, we estimated OR sand corresponding 95% confidence intervals (CI) for each subtype using polytomous logistic regression.Results: Compared with those without a diabetes history, women with type II diabetes had a 38% (95% CI, 1.01-1.89) increased odds of triple-negative breast cancer (TNBC). Current and longer term recent metformin use (13-24 months of treatment within the 24-month period prior to breast cancer diagnosis) was associated with elevated odds of TNBC (OR = 1.54; 95% CI, 1.07-2.22 and OR = 1.80; 95% CI, 1.13-2.85, respectively).Conclusions: The odds of having a triple-negative rather than ER+/HER2(-) breast cancer is greater for women with type II diabetes, and particularly for those who were users of metformin. This finding is supported by some preclinical data suggesting that diabetes may be more strongly associated with risk of triple-negative disease.Impact: Our study provides novel evidence regarding potential differential effects of type II diabetes and metformin use on risk of different molecular subtypes of breast cancer.