Goodwin Pamela J, Parulekar Wendy R, Gelmon Karen A, Shepherd Lois E, Ligibel Jennifer A, Hershman Dawn L, Rastogi Priya, Mayer Ingrid A, Hobday Timothy J, Lemieux Julie, Thompson Alastair M, Pritchard Kathleen I, Whelan Timothy J, Mukherjee Som D, Chalchal Haji I, Oja Conrad D, Tonkin Katia S, Bernstein Vanessa, Chen Bingshu E, Stambolic Vuk
Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada (PJG); NCIC Clinical Trials Group, Cancer Research Institute, Queen's University, Kingston, Ontario, Canada (WRP, LES, BEC); NCIC Clinical Trials Group, British Columbia Cancer Agency, University of British Columbia, Vancouver, British Columbia, Canada (KAG); Dana Farber Cancer Institute, Harvard Medical School, Boston, MA (JAL); Columbia University Medical Center, New York, NY (DLH); National Surgical Adjuvant Breast and Bowel Project, University of Pittsburgh Cancer Institute, University of Pittsburgh, Pittsburgh, PA (PR); Vanderbilt-Ingram Medical Center, Vanderbilt University Medical Center, Nashville, TN (IAM); Mayo Clinic College of Medicine, Rochester, MN (TJH); Centre de recherche du CHU de Québec, Unité de recherche en santé des populations Hôpital du Saint-Sacrement, Quebec, Quebec, Canada (JL); National Cancer Research Institute Breast Clinical Studies Group, London, UK (AMT); Sunnybrook Odette Cancer Center, University of Toronto, Toronto, Ontario, Canada (KIP); Juravinski Cancer Center at Hamilton Health Sciences, McMaster University, Hamilton, Ontario, Canada (TJW, SDM); Allan Blair Cancer Centre, Regina, Saskatchewan, Canada (HIC); British Columbia Cancer Agency, Fraser Valley Center, Surrey, British Columbia, Canada (CDO); University of Alberta, Cross Cancer Institute, Edmonton, Alberta, Canada (KST); British Columbia Cancer Agency - Vancouver Island Center, University of British Columbia, British Columbia, Canada (VB); Ontario Cancer Institute, University Health Network, Princess Margaret Hospital, University of Toronto, Toronto, Ontario, Canada (VS).
J Natl Cancer Inst. 2015 Mar 4;107(3). doi: 10.1093/jnci/djv006. Print 2015 Mar.
Metformin may improve metabolic factors (insulin, glucose, leptin, highly sensitive C-reactive protein [hs-CRP]) associated with poor breast cancer outcomes. The NCIC Clinical Trials Group (NCIC CTG) MA.32 investigates effects of metformin vs placebo on invasive disease-free survival and other outcomes in early breast cancer. Maintaining blinding of investigators to outcomes, we conducted a planned, Data Safety Monitoring Committee-approved, analysis of the effect of metformin vs placebo on weight and metabolic factors at six months, including examination of interactions with baseline body mass index (BMI) and insulin, in the first 492 patients with paired blood samples.
Eligible nondiabetic subjects with T1-3, N0-3, M0 breast cancer who had completed surgery and (neo)adjuvant chemotherapy (if given) provided fasting plasma samples at random assignment and at six months. Glucose was measured locally; blood was aliquoted, frozen, and stored at -80°C. Paired plasma aliquots were analyzed for insulin, hs-CRP, and leptin. Spearman correlation coefficients were calculated and comparisons analyzed using Wilcoxon signed rank test. All statistical tests were two-sided.
Mean age was 52.1±9.5 years in the metformin group and 52.6 ± 9.8 years in the placebo group. Arms were balanced for estrogen/progesterone receptor, BMI, prior (neo)adjuvant chemotherapy, and stage. At six months, decreases in weight and blood variables were statistically significantly greater in the metformin arm (vs placebo) in univariate analyses: weight -3.0%, glucose -3.8%, insulin -11.1%, homeostasis model assessment -17.1%, leptin -20.2%, hs-CRP -6.7%; all P values were less than or equal to .03. There was no statistically significant interaction of change in these variables with baseline BMI or insulin.
Metformin statistically significantly improved weight, insulin, glucose, leptin, and CRP at six months. Effects did not vary by baseline BMI or fasting insulin.
二甲双胍可能改善与乳腺癌不良预后相关的代谢因素（胰岛素、葡萄糖、瘦素、高敏C反应蛋白[hs-CRP]）。加拿大国家癌症研究所临床试验组（NCIC CTG）的MA.32研究旨在探究二甲双胍与安慰剂对早期乳腺癌无侵袭性疾病生存期及其他预后的影响。在研究者对研究结果不知情的情况下，我们对前492例有配对血样的患者进行了一项经数据安全监测委员会批准的计划分析，比较二甲双胍与安慰剂在6个月时对体重和代谢因素的影响，包括与基线体重指数（BMI）和胰岛素的相互作用。
符合条件的T1-3、N0-3、M0期非糖尿病乳腺癌患者，在完成手术及（新）辅助化疗（若接受）后，于随机分组时和6个月时提供空腹血浆样本。葡萄糖在当地进行检测；血液进行分装、冷冻，并储存在-80°C。对配对的血浆样本分析胰岛素、hs-CRP和瘦素。计算Spearman相关系数，并使用Wilcoxon符号秩检验进行比较分析。所有统计检验均为双侧检验。
二甲双胍组的平均年龄为52.1±9.5岁，安慰剂组为52.6±9.8岁。两组在雌激素/孕激素受体、BMI、既往（新）辅助化疗及分期方面均衡可比。在6个月时，单因素分析显示二甲双胍组（与安慰剂组相比）体重和血液变量的下降在统计学上显著更大：体重下降3.0%，葡萄糖下降3.8%，胰岛素下降11.1%，稳态模型评估下降17.1%，瘦素下降20.2%，hs-CRP下降6.7%；所有P值均小于或等于0.03。这些变量的变化与基线BMI或胰岛素之间无统计学显著的相互作用。
二甲双胍在6个月时能使体重、胰岛素、葡萄糖、瘦素和CRP在统计学上显著改善。其效果不因基线BMI或空腹胰岛素而有所不同。
