Effect of metformin versus placebo on metabolic factors in the MA.32 randomized breast cancer trial.

NPJ Breast Cancer
Pamela J GoodwinVuk Stambolic

Abstract

Metformin may exert anticancer effects through indirect (mediated by metabolic changes) or direct mechanisms. The goal was to examine metformin impact on metabolic factors in non-diabetic subjects and determine whether this impact varies by baseline BMI, insulin, and rs11212617 SNP in CCTG MA.32, a double-blind placebo-controlled randomized adjuvant breast cancer (BC) trial. 3649 subjects with T1-3, N0-3, M0 BC were randomized; pretreatment and 6-month on-treatment fasting plasma was centrally assayed for insulin, leptin, highly sensitive C-reactive protein (hsCRP). Glucose was measured locally and homeostasis model assessment (HOMA) calculated. Genomic DNA was analyzed for the rs11212617 SNP. Absolute and relative change of metabolic factors (metformin versus placebo) were compared using Wilcoxon rank and t-tests. Regression models were adjusted for baseline differences and assessed interactions with baseline BMI, insulin, and the SNP. Mean age was 52 years. The majority had T2/3, node positive, hormone receptor positive, HER2 negative BC treated with (neo)adjuvant chemotherapy and hormone therapy. Median baseline body mass index (BMI) was 27.4 kg/m2 (metformin) and 27.3 kg/m2 (placebo). Median weight change was -1.4 kg (metfo...Continue Reading

References

Feb 8, 2002·The New England Journal of Medicine·William C KnowlerUNKNOWN Diabetes Prevention Program Research Group
Apr 26, 2005·BMJ : British Medical Journal·Josie M M EvansAndrew D Morris
Dec 17, 2008·Clinical Breast Cancer·Pamela J GoodwinI George Fantus
Dec 28, 2010·Nature Genetics·UNKNOWN GoDARTS and UKPDS Diabetes Pharmacogenetics Study GroupEwan R Pearson
Feb 23, 2012·Journal of Molecular Endocrinology·Ryan J O DowlingPamela J Goodwin
Jul 4, 2012·Diabetes Care·Jose C FlorezUNKNOWN Diabetes Prevention Program Research Group
Aug 31, 2012·Breast Cancer Research and Treatment·Saroj NiraulaPamela J Goodwin
Oct 26, 2013·British Journal of Cancer·M CazzanigaB Bonanni
Jun 13, 2014·The Journal of Clinical Endocrinology and Metabolism·L Keoki WilliamsDavid E Lanfear
Mar 6, 2015·Journal of the National Cancer Institute·Pamela J GoodwinVuk Stambolic

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