Obesity As a Risk Factor for Anthracyclines and Trastuzumab Cardiotoxicity in Breast Cancer: A Systematic Review and Meta-Analysis

J Clin Oncol. 2016 Sep 10;34(26):3157-65. doi: 10.1200/JCO.2016.67.4846. Epub 2016 Jul 25.

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.

Publication types

  • Meta-Analysis
  • Review
  • Systematic Review

MeSH terms

  • Anthracyclines / adverse effects*
  • Antibiotics, Antineoplastic / adverse effects*
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects*
  • Body Mass Index
  • Breast Neoplasms / complications*
  • Breast Neoplasms / diagnosis
  • Breast Neoplasms / drug therapy*
  • Cardiotoxicity
  • Female
  • Heart Diseases / chemically induced*
  • Heart Diseases / diagnosis
  • Humans
  • Obesity / complications*
  • Obesity / diagnosis
  • Odds Ratio
  • Risk Assessment
  • Risk Factors
  • Trastuzumab / adverse effects*

Substances

  • Anthracyclines
  • Antibiotics, Antineoplastic
  • Trastuzumab