Effect of metformin versus placebo on metabolic factors in the MA.32 randomized breast cancer trial
| Autor: | Daniel Rea, Marguerite Ennis, Vuk Stambolic, Timothy J. Hobday, Ingrid A. Mayer, Manuela Rabaglio-Poretti, Julie Lemieux, Anagha Gurjal, Bingshu E. Chen, Rachel Vander Meer, Andrea Molckovsky, Dawn L. Hershman, Karen A. Gelmon, Timothy J. Whelan, Margot J. Burnell, Priya Rastogi, Jennifer A. Ligibel, Ryan J. O. Dowling, Alastair M. Thompson, Pamela J. Goodwin, Wendy R. Parulekar, Lois E. Shepherd |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
medicine.medical_specialty medicine.medical_treatment Placebo Article 03 medical and health sciences 0302 clinical medicine Breast cancer Internal medicine medicine Pharmacology (medical) Radiology Nuclear Medicine and imaging RC254-282 business.industry Insulin Leptin Weight change nutritional and metabolic diseases Neoplasms. Tumors. Oncology. Including cancer and carcinogens Translational research medicine.disease Cancer metabolism Metformin 030104 developmental biology Endocrinology Oncology 030220 oncology & carcinogenesis Hormone therapy business Body mass index medicine.drug |
| Zdroj: | npj Breast Cancer, Vol 7, Iss 1, Pp 1-8 (2021) NPJ Breast Cancer |
| ISSN: | 2374-4677 |
| Popis: | 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 (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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|