Epidemiology Branch, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, USA.
Westat, Durham, USA.
Ann Oncol. 2021 Mar;32(3):351-359. doi: 10.1016/j.annonc.2020.12.008. Epub 2021 Jan 29.
Type 2 diabetes (T2D) has been associated with increased breast cancer risk, but commonly prescribed antidiabetic medications such as metformin may reduce risk. Few studies have investigated T2D and medications together in relation to breast cancer.
Data came from 44 541 Sister Study participants aged 35 to 74 years at enrollment (2003-2009) who satisfied eligibility criteria, followed through 15 September 2017. Information on time-varying, self-reported, physician-diagnosed, prevalent and incident T2D, use of antidiabetic medications, and covariates was obtained from baseline and follow-up questionnaires. Incident breast cancers were confirmed with medical records. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated.
During follow-up (median, 8.6 years), 2678 breast cancers were diagnosed at least 1 year after enrollment. There were 3227 women (7.2%) with prevalent and 2389 (5.3%) with incident T2D, among whom 61% (n = 3386) were ever treated with metformin. There was no overall association between T2D and breast cancer risk (HR 0.99; 95% CI, 0.87-1.13). However, T2D was associated with increased risk of triple-negative breast cancer (HR 1.40; 95% CI, 0.90-2.16). Compared with not having T2D, T2D with metformin use was not associated with overall breast cancer risk (HR 0.98; 95% CI, 0.83-1.15), but it was associated with decreased risk of estrogen receptor (ER)-positive breast cancer (HR 0.86; 95% CI 0.70-1.05) and increased risk of ER-negative (HR 1.25; 95% CI, 0.84-1.88) and triple-negative breast cancer (HR 1.74; 95% CI, 1.06-2.83). The inverse association with ER-positive cancer was stronger for longer duration (≥10 year) metformin use (HR 0.62; 95% CI, 0.38-1.01; P for trend = 0.09). Results were supported by sensitivity analyses.
Our findings suggest that associations between T2D and breast cancer may differ by hormone receptor status and that associations between T2D and ER-positive breast cancer may be reduced by long-term metformin use.
2 型糖尿病（T2D）与乳腺癌风险增加有关，但常用的降糖药物如二甲双胍可能会降低风险。很少有研究同时探讨 T2D 和药物与乳腺癌之间的关系。
数据来自于 44541 名年龄在 35 至 74 岁之间（2003-2009 年入组）、符合入组条件的“姐妹研究”参与者，随访至 2017 年 9 月 15 日。通过基线和随访问卷获取了关于时间变化的、自我报告的、医生诊断的、现患和新发 T2D、降糖药物使用情况以及混杂因素的信息。通过病历记录来确认新发乳腺癌。使用风险比（HR）和 95%置信区间（CI）来进行估计。
在随访期间（中位数 8.6 年），至少在入组后 1 年被诊断出 2678 例乳腺癌。其中 3227 名女性（7.2%）患有现患 T2D，2389 名（5.3%）患有新发 T2D，其中 61%（n=3386）曾接受二甲双胍治疗。T2D 与乳腺癌风险之间没有总体关联（HR 0.99；95%CI，0.87-1.13）。然而，T2D 与三阴性乳腺癌的风险增加相关（HR 1.40；95%CI，0.90-2.16）。与没有 T2D 相比，T2D 伴二甲双胍使用与总体乳腺癌风险无关（HR 0.98；95%CI，0.83-1.15），但与雌激素受体（ER）阳性乳腺癌风险降低相关（HR 0.86；95%CI，0.70-1.05），与 ER 阴性（HR 1.25；95%CI，0.84-1.88）和三阴性乳腺癌（HR 1.74；95%CI，1.06-2.83）风险增加相关。二甲双胍使用时间较长（≥10 年）与 ER 阳性癌症的负相关更强（HR 0.62；95%CI，0.38-1.01；P 趋势=0.09）。敏感性分析结果支持了上述发现。
我们的研究结果表明，T2D 与乳腺癌之间的关联可能因激素受体状态而异，而 T2D 与 ER 阳性乳腺癌之间的关联可能通过长期使用二甲双胍来降低。
