Vissers Pauline A J, Cardwell Chris R, van de Poll-Franse Lonneke V, Young Ian S, Pouwer Frans, Murray Liam J
CoRPS-Center of Research on Psychology in Somatic Diseases, Department of Medical and Clinical Psychology, Tilburg University, P. O. Box 90153, 5000 LE, Tilburg, The Netherlands,
Breast Cancer Res Treat. 2015 Apr;150(2):427-37. doi: 10.1007/s10549-015-3331-5. Epub 2015 Mar 12.
This study assessed the association between glucose-lowering drug (GLD) use, including metformin, sulphonylurea derivatives and insulin, after breast cancer diagnosis and breast cancer-specific and all-cause mortality. 1763 breast cancer patients, diagnosed between 1998 and 2010, with type 2 diabetes were included. Cancer information was retrieved from English cancer registries, prescription data from the UK Clinical Practice Research Datalink and mortality data from the Office of National Statistics (up to January 2012). Time-varying Cox regression models were used to calculate HRs and 95 % CIs for the association between GLD use and breast cancer-specific and all-cause mortality. In 1057 patients with diabetes before breast cancer, there was some evidence that breast cancer-specific mortality decreased with each year of metformin use (adjusted HR 0.88; 95 % CI 0.75-1.04), with a strong association seen with over 2 years of use (adjusted HR 0.47; 95 % CI 0.26-0.82). Sulphonylurea derivative use for less than 2 years was associated with increased breast cancer-specific mortality (adjusted HR 1.70; 95 % CI 1.18-2.46), but longer use was not (adjusted HR 0.94; 95 % CI 0.54-1.66). In 706 patients who developed diabetes after breast cancer, similar patterns were seen for metformin, but sulphonylurea derivative use was strongly associated with cancer-specific mortality (adjusted HR 3.64; 95 % CI 2.16-6.16), with similar estimates for short- and long-term users. This study provides some support for an inverse association between, mainly long-term, metformin use and (breast cancer-specific) mortality. In addition, sulphonylurea derivative use was associated with increased breast cancer-specific mortality, but this should be interpreted cautiously, as it could reflect selective prescribing in advanced cancer patients.
本研究评估了乳腺癌诊断后使用降糖药物（GLD）（包括二甲双胍、磺脲类衍生物和胰岛素）与乳腺癌特异性死亡率及全因死亡率之间的关联。研究纳入了1998年至2010年间诊断为2型糖尿病的1763例乳腺癌患者。癌症信息从英国癌症登记处获取，处方数据来自英国临床实践研究数据链，死亡率数据来自国家统计局（截至2012年1月）。采用时变Cox回归模型计算GLD使用与乳腺癌特异性死亡率及全因死亡率之间关联的风险比（HR）和95%置信区间（CI）。在1057例乳腺癌前患有糖尿病的患者中，有证据表明，每年使用二甲双胍可使乳腺癌特异性死亡率降低（调整后HR为0.88；95%CI为0.75 - 1.04），使用超过2年时这种关联更为显著（调整后HR为0.47；95%CI为0.26 - 0.82）。使用磺脲类衍生物不足2年与乳腺癌特异性死亡率增加相关（调整后HR为1.70；95%CI为1.18 - 2.46），但使用时间较长则无此关联（调整后HR为0.94；95%CI为0.54 - 1.66）。在706例乳腺癌后发生糖尿病的患者中，二甲双胍呈现出类似的模式，但使用磺脲类衍生物与癌症特异性死亡率密切相关（调整后HR为3.64；95%CI为2.16 - 6.16），短期和长期使用者的估计值相似。本研究为主要是长期使用二甲双胍与（乳腺癌特异性）死亡率之间的负相关提供了一定支持。此外，使用磺脲类衍生物与乳腺癌特异性死亡率增加相关，但对此应谨慎解读，因为这可能反映了晚期癌症患者的选择性用药情况。
