Effect of Metformin Versus Placebo on New Primary Cancers in Canadian Cancer Trials Group MA.32: A Secondary Analysis of a Phase III Randomized Double-Blind Trial in Early Breast Cancer.
Effect of Metformin Versus Placebo on New Primary Cancers in Canadian Cancer Trials Group MA.32: A Secondary Analysis of a Phase III Randomized Double-Blind Trial in Early Breast Cancer.
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DOI：
10.1200/jco.23.00296
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发表时间：
2023-12-10
期刊：
影响因子：
--
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中科院分区：
文献类型：
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临床试验通常包括在不同时间成熟的多个终点。初始报告通常基于主要终点，当关键计划的共同主要或次要分析尚未可用时，可发表。临床试验更新提供了一个机会，可以传播在JCO或其他地方发表的研究的其他结果，这些研究的主要终点已经报告。在流行病学和临床前研究中，美托洛尔与较低的癌症风险相关。在MA.32随机辅助乳腺癌试验中，二甲双胍（与安慰剂相比）不影响无侵袭性疾病或总生存期。在这里，我们报告二甲双胍对新发癌症风险的影响。在2010年至2013年期间，3，649例年龄小于75岁且无糖尿病的高危T1-3，N 0 -3 M0乳腺癌（任何雌激素受体，孕酮受体，人表皮生长因子受体2）乳腺癌患者被随机分配至二甲双胍850 mg口服每日两次或安慰剂每日两次，持续5年。确定新发原发性浸润性癌症（同侧乳腺外）作为首发事件。采用竞争风险法描述至事件发生的时间;采用调整年龄、BMI、吸烟和饮酒的双侧似然比检验比较二甲双胍组与安慰剂组。共有184例患者发生新发浸润性癌症：二甲双胍组102例，安慰剂组82例，风险比（HR）为1.25; 95% CI为0.94 - 1.68; P = 0.13。其中包括48例对侧浸润性乳腺癌（二甲双胍组27例，安慰剂组21例），HR，1. 29; 95% CI，0. 72 - 2. 27; P = 0. 40; 136例新发非乳腺原发性癌症（二甲双胍组75例，安慰剂组61例），HR，1. 24; 95% CI，0. 88 - 1. 74; P = 0. 21。在这些非糖尿病乳腺癌患者中，二甲双胍并没有降低新发癌症的风险。二甲双胍（与安慰剂相比）不能预防非糖尿病早期乳腺癌患者的新癌症。
Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned coprimary or secondary analyses are not yet available. Clinical trial updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported. Metformin has been associated with lower cancer risk in epidemiologic and preclinical research. In the MA.32 randomized adjuvant breast cancer trial, metformin (v placebo) did not affect invasive disease-free or overall survival. Here, we report metformin effects on the risk of new cancer. Between 2010 and 2013, 3,649 patients with breast cancer younger than 75 years without diabetes with high-risk T1-3, N0-3 M0 breast cancer (any estrogen receptor, progesterone receptor, human epidermal growth factor receptor 2) were randomly assigned to metformin 850 mg orally twice a day or placebo twice a day for 5 years. New primary invasive cancers (outside the ipsilateral breast) developing as a first event were identified. Time to events was described by the competing risks method; two-sided likelihood ratio tests adjusting for age, BMI, smoking, and alcohol intake were used to compare metformin versus placebo arms. A total of 184 patients developed new invasive cancers: 102 metformin and 82 placebo, hazard ratio (HR), 1.25; 95% CI, 0.94 to 1.68; P = .13. These included 48 contralateral invasive breast cancers (27 metformin v 21 placebo), HR, 1.29; 95% CI, 0.72 to 2.27; P = .40 and 136 new nonbreast primary cancers (75 metformin v 61 placebo), HR, 1.24; 95% CI, 0.88 to 1.74; P = .21. Metformin did not reduce the risk of new cancer development in these nondiabetic patients with breast cancer. Metformin (v placebo) did not prevent new cancers in nondiabetic patients with early breast cancer.
影响因子：
8.2
作者：
van Leeuwen, N.;Nijpels, G.;Becker, M. L.;Deshmukh, H.;Zhou, K.;Stricker, B. H. C.;Uitterlinden, A. G.;Hofman, A.;van 't Riet, E.;Palmer, C. N. A.;Guigas, B.;Slagboom, P. E.;Durrington, P.;Calle, R. A.;Neil, A.;Hitman, G.;Livingstone, S. J.;Colhoun, H.;Holman, R. R.;McCarthy, M. I.;Dekker, J. M.;'t Hart, L. M.;Pearson, E. R.
通讯作者：
Pearson, E. R.
影响因子：
4.5
作者：
Luizon MR;Eckalbar WL;Wang Y;Jones SL;Smith RP;Laurance M;Lin L;Gallins PJ;Etheridge AS;Wright F;Zhou Y;Molony C;Innocenti F;Yee SW;Giacomini KM;Ahituv N
通讯作者：
Ahituv N