title: Obesity As a Risk Factor for Anthracyclines and Trastuzumab Cardiotoxicity in Breast Cancer: A Systematic Review and Meta-Analysis.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  Our findings in a largely unadjusted analysis suggest that overweight and obesity are risk factors for cardiotoxicity from anthracyclines and sequential anthracyclines and trastuzumab.
authors.affiliation: 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.
authors.forename: Charles
authors.initials: C
authors.lastname: Guenancia
authors.affiliation: 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.
authors.forename: Annick
authors.initials: A
authors.lastname: Lefebvre
authors.affiliation: 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.
authors.forename: Daniela
authors.initials: D
authors.lastname: Cardinale
authors.affiliation: 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.
authors.forename: Anthony F
authors.initials: AF
authors.lastname: Yu
authors.affiliation: 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.
authors.forename: Sylvain
authors.initials: S
authors.lastname: Ladoire
authors.affiliation: 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.
authors.forename: François
authors.initials: F
authors.lastname: Ghiringhelli
authors.affiliation: 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.
authors.forename: Marianne
authors.initials: M
authors.lastname: Zeller
authors.affiliation: 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.
authors.forename: Luc
authors.initials: L
authors.lastname: Rochette
authors.affiliation: 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.
authors.forename: Yves
authors.initials: Y
authors.lastname: Cottin
authors.affiliation: 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.
authors.forename: Catherine
authors.initials: C
authors.lastname: Vergely
mesh_terms: D018943:Anthracyclines / Q000009:adverse effects*; D000903:Antibiotics, Antineoplastic / Q000009:adverse effects*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects*; D015992:Body Mass Index; D001943:Breast Neoplasms / Q000150:complications* / Q000175:diagnosis / Q000188:drug therapy*; D066126:Cardiotoxicity; D005260:Female; D006331:Heart Diseases / Q000139:chemically induced* / Q000175:diagnosis; D006801:Humans; D009765:Obesity / Q000150:complications* / Q000175:diagnosis; D016017:Odds Ratio; D018570:Risk Assessment; D012307:Risk Factors; D000068878:Trastuzumab / Q000009:adverse effects*
chemical_list: D018943:Anthracyclines; D000903:Antibiotics, Antineoplastic; D000068878:Trastuzumab