Charles Guenancia1, Annick Lefebvre2, Daniela Cardinale2, Anthony F Yu2, Sylvain Ladoire2, François Ghiringhelli2, Marianne Zeller2, Luc Rochette2, Yves Cottin2, Catherine Vergely2. 1. Charles Guenancia, Annick Lefebvre, and Yves Cottin, University Hospital; Charles Guenancia, Marianne Zeller, Luc Rochette, Yves Cottin, and Catherine Vergely, Institut National de la Santé et de la Recherche Médicale, U866, Laboratoire de Physiopathologie et Pharmacologie Cardio-Métaboliques; Sylvain Ladoire and François Ghiringhelli, Georges François Leclerc Cancer Center; Sylvain Ladoire and François Ghiringhelli, Institut National de la Santé et de la Recherche Médicale, CRI-866, University of Burgundy, Dijon; Annick Lefebvre, University Hospital, Reims, France; Daniela Cardinale, European Institute of Oncology, Milan, Italy; and Anthony F. Yu, Memorial Sloan Kettering Cancer Center, New York, NY. charles.guenancia@chu-dijon.fr. 2. Charles Guenancia, Annick Lefebvre, and Yves Cottin, University Hospital; Charles Guenancia, Marianne Zeller, Luc Rochette, Yves Cottin, and Catherine Vergely, Institut National de la Santé et de la Recherche Médicale, U866, Laboratoire de Physiopathologie et Pharmacologie Cardio-Métaboliques; Sylvain Ladoire and François Ghiringhelli, Georges François Leclerc Cancer Center; Sylvain Ladoire and François Ghiringhelli, Institut National de la Santé et de la Recherche Médicale, CRI-866, University of Burgundy, Dijon; Annick Lefebvre, University Hospital, Reims, France; Daniela Cardinale, European Institute of Oncology, Milan, Italy; and Anthony F. Yu, Memorial Sloan Kettering Cancer Center, New York, NY.
Abstract
PURPOSE: Patients with metabolic syndrome have a greater risk of cardiovascular disease, although their susceptibility to chemotherapy-induced cardiac disease is not well documented. The aim of this meta-analysis was to assess associations between obesity or being overweight and cardiotoxicity from anthracyclines and sequential anthracyclines and trastuzumab in patients with breast cancer. METHODS: We performed a random-effects analysis and a network meta-analysis and assessed publication bias. We included 15 studies and 8,745 patients with breast cancers who were treated with anthracyclines and sequential anthracyclines and trastuzumab. RESULTS: Combination of obesity and being overweight was significantly associated with a greater risk of developing cardiotoxicity after anthracyclines and a sequential anthracyclines and trastuzumab regimen in patients with breast cancer. Pooled odds ratio for cardiotoxicity was 1.38 (95% CI, 1.06 to 1.80; I(2) = 43%; N = 8,745) for overweight or obesity (body mass index > 25 kg/m(2)), 1.47 (95% CI, 0.95 to 2.28; I(2) = 47%; n = 2,615) for obesity, and 1.15 (95% CI, 0.83 to 1.58; I(2) = 27%; n = 2,708) for overweight. Associations were independent of study design, year of publication, drug regimen (anthracyclines alone v sequential anthracyclines and trastuzumab), or definitions of cardiotoxicity and of overweight or obesity. There was no evidence of publication bias; however, we could not separate the contributions of obesity-related cardiovascular risk factors, such as diabetes and hypertension, from that of obesity itself in this largely unadjusted analysis. CONCLUSION: Our findings in a largely unadjusted analysis suggest that overweight and obesity are risk factors for cardiotoxicity from anthracyclines and sequential anthracyclines and trastuzumab.
PURPOSE:Patients with metabolic syndrome have a greater risk of cardiovascular disease, although their susceptibility to chemotherapy-induced cardiac disease is not well documented. The aim of this meta-analysis was to assess associations between obesity or being overweight and cardiotoxicity from anthracyclines and sequential anthracyclines and trastuzumab in patients with breast cancer. METHODS: We performed a random-effects analysis and a network meta-analysis and assessed publication bias. We included 15 studies and 8,745 patients with breast cancers who were treated with anthracyclines and sequential anthracyclines and trastuzumab. RESULTS: Combination of obesity and being overweight was significantly associated with a greater risk of developing cardiotoxicity after anthracyclines and a sequential anthracyclines and trastuzumab regimen in patients with breast cancer. Pooled odds ratio for cardiotoxicity was 1.38 (95% CI, 1.06 to 1.80; I(2) = 43%; N = 8,745) for overweight or obesity (body mass index > 25 kg/m(2)), 1.47 (95% CI, 0.95 to 2.28; I(2) = 47%; n = 2,615) for obesity, and 1.15 (95% CI, 0.83 to 1.58; I(2) = 27%; n = 2,708) for overweight. Associations were independent of study design, year of publication, drug regimen (anthracyclines alone v sequential anthracyclines and trastuzumab), or definitions of cardiotoxicity and of overweight or obesity. There was no evidence of publication bias; however, we could not separate the contributions of obesity-related cardiovascular risk factors, such as diabetes and hypertension, from that of obesity itself in this largely unadjusted analysis. CONCLUSION: Our findings in a largely unadjusted analysis suggest that overweight and obesity are risk factors for cardiotoxicity from anthracyclines and sequential anthracyclines and trastuzumab.
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