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

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...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Pamela J. Goodwin, Ryan J. O. Dowling, Marguerite Ennis, Bingshu E. Chen, Wendy R. Parulekar, Lois E. Shepherd, Margot J. Burnell, Rachel Vander Meer, Andrea Molckovsky, Anagha Gurjal, Karen A. Gelmon, Jennifer A. Ligibel, Dawn L. Hershman, Ingrid A. Mayer, Timothy J. Whelan, Timothy J. Hobday, Priya Rastogi, Manuela Rabaglio-Poretti, Julie Lemieux, Alastair M. Thompson, Daniel W. Rea, Vuk Stambolic
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/ed8c22cdd63b4d8ab3a69bbf18ba9909
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:ed8c22cdd63b4d8ab3a69bbf18ba9909
record_format	dspace
spelling	oai:doaj.org-article:ed8c22cdd63b4d8ab3a69bbf18ba99092021-12-02T18:06:32ZEffect of metformin versus placebo on metabolic factors in the MA.32 randomized breast cancer trial10.1038/s41523-021-00275-z2374-4677https://doaj.org/article/ed8c22cdd63b4d8ab3a69bbf18ba99092021-06-01T00:00:00Zhttps://doi.org/10.1038/s41523-021-00275-zhttps://doaj.org/toc/2374-4677Abstract 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.Pamela J. GoodwinRyan J. O. DowlingMarguerite EnnisBingshu E. ChenWendy R. ParulekarLois E. ShepherdMargot J. BurnellRachel Vander MeerAndrea MolckovskyAnagha GurjalKaren A. GelmonJennifer A. LigibelDawn L. HershmanIngrid A. MayerTimothy J. WhelanTimothy J. HobdayPriya RastogiManuela Rabaglio-PorettiJulie LemieuxAlastair M. ThompsonDaniel W. ReaVuk StambolicNature PortfolioarticleNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENnpj Breast Cancer, Vol 7, Iss 1, Pp 1-8 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Pamela J. Goodwin Ryan J. O. Dowling Marguerite Ennis Bingshu E. Chen Wendy R. Parulekar Lois E. Shepherd Margot J. Burnell Rachel Vander Meer Andrea Molckovsky Anagha Gurjal Karen A. Gelmon Jennifer A. Ligibel Dawn L. Hershman Ingrid A. Mayer Timothy J. Whelan Timothy J. Hobday Priya Rastogi Manuela Rabaglio-Poretti Julie Lemieux Alastair M. Thompson Daniel W. Rea Vuk Stambolic Effect of metformin versus placebo on metabolic factors in the MA.32 randomized breast cancer trial
description	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 (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.
format	article
author	Pamela J. Goodwin Ryan J. O. Dowling Marguerite Ennis Bingshu E. Chen Wendy R. Parulekar Lois E. Shepherd Margot J. Burnell Rachel Vander Meer Andrea Molckovsky Anagha Gurjal Karen A. Gelmon Jennifer A. Ligibel Dawn L. Hershman Ingrid A. Mayer Timothy J. Whelan Timothy J. Hobday Priya Rastogi Manuela Rabaglio-Poretti Julie Lemieux Alastair M. Thompson Daniel W. Rea Vuk Stambolic
author_facet	Pamela J. Goodwin Ryan J. O. Dowling Marguerite Ennis Bingshu E. Chen Wendy R. Parulekar Lois E. Shepherd Margot J. Burnell Rachel Vander Meer Andrea Molckovsky Anagha Gurjal Karen A. Gelmon Jennifer A. Ligibel Dawn L. Hershman Ingrid A. Mayer Timothy J. Whelan Timothy J. Hobday Priya Rastogi Manuela Rabaglio-Poretti Julie Lemieux Alastair M. Thompson Daniel W. Rea Vuk Stambolic
author_sort	Pamela J. Goodwin
title	Effect of metformin versus placebo on metabolic factors in the MA.32 randomized breast cancer trial
title_short	Effect of metformin versus placebo on metabolic factors in the MA.32 randomized breast cancer trial
title_full	Effect of metformin versus placebo on metabolic factors in the MA.32 randomized breast cancer trial
title_fullStr	Effect of metformin versus placebo on metabolic factors in the MA.32 randomized breast cancer trial
title_full_unstemmed	Effect of metformin versus placebo on metabolic factors in the MA.32 randomized breast cancer trial
title_sort	effect of metformin versus placebo on metabolic factors in the ma.32 randomized breast cancer trial
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/ed8c22cdd63b4d8ab3a69bbf18ba9909
work_keys_str_mv	AT pamelajgoodwin effectofmetforminversusplaceboonmetabolicfactorsinthema32randomizedbreastcancertrial AT ryanjodowling effectofmetforminversusplaceboonmetabolicfactorsinthema32randomizedbreastcancertrial AT margueriteennis effectofmetforminversusplaceboonmetabolicfactorsinthema32randomizedbreastcancertrial AT bingshuechen effectofmetforminversusplaceboonmetabolicfactorsinthema32randomizedbreastcancertrial AT wendyrparulekar effectofmetforminversusplaceboonmetabolicfactorsinthema32randomizedbreastcancertrial AT loiseshepherd effectofmetforminversusplaceboonmetabolicfactorsinthema32randomizedbreastcancertrial AT margotjburnell effectofmetforminversusplaceboonmetabolicfactorsinthema32randomizedbreastcancertrial AT rachelvandermeer effectofmetforminversusplaceboonmetabolicfactorsinthema32randomizedbreastcancertrial AT andreamolckovsky effectofmetforminversusplaceboonmetabolicfactorsinthema32randomizedbreastcancertrial AT anaghagurjal effectofmetforminversusplaceboonmetabolicfactorsinthema32randomizedbreastcancertrial AT karenagelmon effectofmetforminversusplaceboonmetabolicfactorsinthema32randomizedbreastcancertrial AT jenniferaligibel effectofmetforminversusplaceboonmetabolicfactorsinthema32randomizedbreastcancertrial AT dawnlhershman effectofmetforminversusplaceboonmetabolicfactorsinthema32randomizedbreastcancertrial AT ingridamayer effectofmetforminversusplaceboonmetabolicfactorsinthema32randomizedbreastcancertrial AT timothyjwhelan effectofmetforminversusplaceboonmetabolicfactorsinthema32randomizedbreastcancertrial AT timothyjhobday effectofmetforminversusplaceboonmetabolicfactorsinthema32randomizedbreastcancertrial AT priyarastogi effectofmetforminversusplaceboonmetabolicfactorsinthema32randomizedbreastcancertrial AT manuelarabaglioporetti effectofmetforminversusplaceboonmetabolicfactorsinthema32randomizedbreastcancertrial AT julielemieux effectofmetforminversusplaceboonmetabolicfactorsinthema32randomizedbreastcancertrial AT alastairmthompson effectofmetforminversusplaceboonmetabolicfactorsinthema32randomizedbreastcancertrial AT danielwrea effectofmetforminversusplaceboonmetabolicfactorsinthema32randomizedbreastcancertrial AT vukstambolic effectofmetforminversusplaceboonmetabolicfactorsinthema32randomizedbreastcancertrial
_version_	1718378666818273280

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

Ejemplares similares