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

Abstract

International audiencePurposePatients 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.MethodsWe 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.ResultsCombination 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.ConclusionOur findings in a largely unadjusted analysis suggest that overweight and obesity are risk factors for cardiotoxicity from anthracyclines and sequential anthracyclines and trastuzumab

Body Surface Area and Baseline Blood Pressure Predict Subclinical Anthracycline Cardiotoxicity in Women Treated for Early Breast Cancer

“…In addition, the selected nature of our cohort, which included very few women with BMI >35kg/m 2 , may have biased against a signal. Nonetheless, the relationship between body morphology and composition with anthracycline/Trastuzumab cardiotoxicity has become a matter of increasing interest, with a detailed systematic review and meta-analysis being only recently published [27]. In keeping with our findings, this concludes that ‘overweight and obesity are risk factors for cardiotoxicity from anthracyclines and sequential anthracyclines and trastuzumab’.…”

“…In keeping with our findings, this concludes that ‘overweight and obesity are risk factors for cardiotoxicity from anthracyclines and sequential anthracyclines and trastuzumab’. Such associations are postulated to be driven in part by reduced levels of the adipocytokine (adipocyte-derived hormone) adiponectin in obese patients: adiponectin-knockout mice appear more susceptible to doxorubicin-induced cardiac contractile dysfunction, whilst exogenously-administered adiponectin protects such mice, and enhances cardiac function in wild-type mice treated with doxorubicin (reviewed in [27]).…”

Cardiotoxicity From Human Epidermal Growth Factor Receptor‐2 (HER2) Targeted Therapies

“…Higher body mass index has also been shown to significantly increase the odds of cardiac dysfunction associated with anthracycline or sequential treatment with anthracycline and trastuzumab. In a meta‐analysis of 15 studies, a body mass index >25 or >30 kg/m 2 was associated with 1.32 (95% CI, 1.06–1.80) and 1.47 (95% CI, 0.95–2.28) times the odds of cardiotoxicity compared with a normal body mass index 58. Cardiac risk scores have been developed to predict the risk of cardiotoxicity associated with trastuzumab, including several risk factors such as age, hypertension, diabetes mellitus, coronary artery disease, atrial fibrillation or flutter, renal dysfunction, and use of adjuvant chemotherapy 11, 57.…”

Tumor-linked HER2 expression: association with obesity and lipid-related microenvironment

“…Of note, circulating HER2 is derived from the extracellular domain, which can be measured after its release in the blood stream. On the other hand, studies have indicated that obesity might increase the risk of cardiac toxicity in breast cancer patients who received trastuzumab (HER2-targeted monoclonal antibody) therapy [108], [109], [110]. Evidence shows that HER2 plays important physiological roles in the development of the heart and cardiomyocyte survival [111], [112].…”