Ko Kwang-Pil, Ma Seung Hyun, Yang Jae-Jeong, Hwang Yunji, Ahn Choonghyun, Cho Young-Min, Noh Dong-Young, Park Byung-Joo, Han Wonshik, Park Sue K
Department of Preventive Medicine, Gacheon University College of Medicine, Inchon, Republic of Korea.
Breast Cancer Res Treat. 2015 Sep;153(2):361-70. doi: 10.1007/s10549-015-3519-8. Epub 2015 Aug 21.
Previous observational studies have suggested that metformin in diabetes patients may reduce breast cancer risk more than the reductions from other anti-diabetes medications. This randomized, double-blind, placebo-controlled trial was performed to evaluate the efficacy of metformin for controlling physical and metabolic profiles related to prognosis and adverse events in non-diabetic breast cancer patients. Female breast cancer patients (N = 105), at least 6 months post-mastectomy, with obesity (≥25 kg/m(2)) and/or pre-diabetes (fasting blood sugar levels ≥100 mg/dL), were randomly assigned to three groups (placebo, metformin 500 mg, and metformin 1000 mg) stratified by tamoxifen use. A linear mixed model for repeated measurements among three groups and ANOVA for profile differences during 6 months of treatment were used for the intention-to-treat analysis. The metformin 1000 mg group had a significantly greater decline in glucose and HbA1c levels between treatment weeks 0 and 6 month (p = 0.008 and 0.009, respectively), and the declines increased with an increase in body mass index (BMI) level (p interaction with BMI = 0.007 and 0.067, respectively). A marginally significant different effect from the metformin 1000 mg treatment was detected for glucose and HbA1c levels (p interaction = 0.084 and 0.063, respectively) in the intention-to-treat analysis. Metformin 1000 mg treatment had a favorable effect on controlling glucose and HbA1C levels in obese non-diabetic breast cancer patients, indicating prognostic importance. Further trials are needed to elucidate the risk-benefit ratio of long-term use of metformin.
先前的观察性研究表明，糖尿病患者使用二甲双胍可能比使用其他抗糖尿病药物更能降低患乳腺癌的风险。本随机、双盲、安慰剂对照试验旨在评估二甲双胍对控制非糖尿病乳腺癌患者与预后和不良事件相关的身体和代谢状况的疗效。女性乳腺癌患者（N = 105），在乳房切除术后至少6个月，患有肥胖症（≥25 kg/m²）和/或糖尿病前期（空腹血糖水平≥100 mg/dL），根据他莫昔芬的使用情况分层随机分为三组（安慰剂组、500 mg二甲双胍组和1000 mg二甲双胍组）。采用三组间重复测量的线性混合模型和治疗6个月期间的概况差异方差分析进行意向性分析。在治疗第0周和第6个月之间，1000 mg二甲双胍组的血糖和糖化血红蛋白水平显著下降更多（分别为p = 0.008和0.009），且下降幅度随体重指数（BMI）水平的升高而增加（与BMI的交互作用p分别为0.007和0.067）。在意向性分析中，对于血糖和糖化血红蛋白水平，检测到1000 mg二甲双胍治疗有边缘显著的不同效果（交互作用p分别为0.084和0.063）。1000 mg二甲双胍治疗对肥胖非糖尿病乳腺癌患者控制血糖和糖化血红蛋白水平有良好效果，表明其对预后具有重要意义。需要进一步的试验来阐明长期使用二甲双胍的风险效益比。
