| Autor: |
Goodwin PJ; Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, and Department of Medicine, University of Toronto, Toronto, ON, Canada. Pamela.Goodwin@sinaihealthsystem.ca., Dowling RJO; Hoffman-La Roche Limited, Mississauga, ON, Canada., Ennis M; Applied Statistician, Markham, ON, Canada., Chen BE; Canadian Cancer Trials Group, Queen's University, Kingston, ON, Canada., Parulekar WR; Canadian Cancer Trials Group, Queen's University, Kingston, ON, Canada., Shepherd LE; Canadian Cancer Trials Group, Queen's University, Kingston, ON, Canada., Burnell MJ; Department of Oncology, Saint John Regional Hospital, St. John, NB, Canada., Vander Meer R; Department of Oncology, Niagara Health System, St. Catharines, ON, Canada., Molckovsky A; Department of Medical Oncology, Grand River Regional Cancer Centre, Kitchener, ON, Canada., Gurjal A; Abbotsford Centre, British Columbia Cancer Agency, Abbotsford, BC, Canada., Gelmon KA; University of British Columbia, BC Cancer Agency, Vancouver, BC, Canada., Ligibel JA; Dana-Farber Cancer Institute, Boston, MA, USA., Hershman DL; Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center, Columbia, NY, USA., Mayer IA; Vanderbilt University, Nashville, TN, USA., Whelan TJ; McMaster University, Juravinski Cancer Centre, Hamilton, ON, Canada., Hobday TJ; Mayo Clinic, Rochester, MN, USA., Rastogi P; NRG Oncology and University of Pittsburgh Medical Center, Pittsburgh, PA, USA., Rabaglio-Poretti M; IBCSG and Department of Oncology, Bern University Hospital, University of Bern, Berne, Switzerland., Lemieux J; CHU de Québec-Université Laval, Québec, QC, Canada., Thompson AM; Baylor College of Medicine, Houston, TX, USA., Rea DW; Cancer Research UK Clinical Trials Unit (CRCTU), Institute of Cancer and Genomic Sciences, University of Birmingham, Birmingham, UK., Stambolic V; Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.; Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada. |
| Abstrakt: |
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/m 2 (metformin) and 27.3 kg/m 2 (placebo). Median weight change was -1.4 kg (metformin) vs +0.5 kg (placebo). Significant improvements were seen in all metabolic factors, with 6 month standardized ratios (metformin/placebo) of 0.85 (insulin), 0.83 (HOMA), 0.80 (leptin), and 0.84 (hsCRP), with no qualitative interactions with baseline BMI or insulin. Changes did not differ by rs11212617 allele. Metformin (vs placebo) led to significant improvements in weight and metabolic factors; these changes did not differ by rs11212617 allele status. |
