Guenancia Charles, Lefebvre Annick, Cardinale Daniela, Yu Anthony F, Ladoire Sylvain, Ghiringhelli François, Zeller Marianne, Rochette Luc, Cottin Yves, Vergely Catherine
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.
J Clin Oncol. 2016 Sep 10;34(26):3157-65. doi: 10.1200/JCO.2016.67.4846. Epub 2016 Jul 25.
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.
代谢综合征患者患心血管疾病的风险更高，尽管其对化疗所致心脏病的易感性尚无充分文献记载。本荟萃分析的目的是评估肥胖或超重与乳腺癌患者使用蒽环类药物、序贯蒽环类药物和曲妥珠单抗所致心脏毒性之间的关联。
我们进行了随机效应分析和网状荟萃分析，并评估了发表偏倚。我们纳入了15项研究以及8745例接受蒽环类药物、序贯蒽环类药物和曲妥珠单抗治疗的乳腺癌患者。
肥胖与超重并存与乳腺癌患者在接受蒽环类药物以及序贯蒽环类药物和曲妥珠单抗治疗后发生心脏毒性的风险显著相关。超重或肥胖（体重指数>25kg/m²）导致心脏毒性的合并比值比为1.38（95%CI，1.06至1.80；I² = 43%；N = 8745），肥胖导致心脏毒性的合并比值比为1.47（95%CI，0.95至2.28；I² = 47%；n = 2615），超重导致心脏毒性的合并比值比为1.15（95%CI，0.83至1.58；I² = 27%；n = 2708）。这些关联独立于研究设计、发表年份、药物方案（单纯蒽环类药物与序贯蒽环类药物和曲妥珠单抗），以及心脏毒性和超重或肥胖的定义。没有发表偏倚的证据；然而，在这项基本未进行调整的分析中，我们无法区分肥胖相关的心血管危险因素（如糖尿病和高血压）与肥胖本身的影响。
我们在一项基本未进行调整的分析中的研究结果表明，超重和肥胖是蒽环类药物、序贯蒽环类药物和曲妥珠单抗所致心脏毒性的危险因素。
