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Overweight, obesity risk factors for cardiotoxicity from anthracyclines, trastuzumab
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Obese and overweight patients who received anthracyclines alone or sequentially with trastuzumab experienced an increased risk for cardiotoxicity, according to results of a meta-analysis.
Patients with metabolic syndrome are known to have an increased risk for cardiovascular disease; however, the risk for cardiac disease associated with chemotherapy has not been well established.
“We were very surprised that obesity was not described in the literature as a classical risk factor of anthracycline and trastuzumab cardiotoxicity, although this risk factor is well known in the general population,” Charles Guenancia, MD, PhD, of the cardiology service at Centre Hospitalier Universitaire de Dijon in Dijon, France, told HemOnc Today. “Obesity is specifically described in breast cancer as a prognostic factor, and we hope that our study could help to explain the over risk for death carried by obese patients with breast cancer.”
Guenancia and colleagues conducted a random-effect meta-analysis of 15 studies — all of which evaluated weight as a risk factor for cardiotoxicity — composed of 8,745 patients with localized or metastatic breast cancer who received trastuzumab (Herceptin, Genentech) or anthracyclines. Ninety-one percent of patients who received trastuzumab also received anthracyclines.
The mean cardiotoxicity rate in the entire cohort was 17% (95% CI, 11-25). The mean cardiotoxicity rate increased to 20% (95% CI, 5-43) among patients who received anthracyclines only (n = 3,898) but decreased to 16% (95% CI, 10-24) among patients who received trastuzumab with or without anthracyclines (n = 4,847).
Researchers then evaluated the risk for cardiotoxicity associated with being overweight (BMI, 25-29.9; n = 2,708) or obese (BMI, 30; n = 2,615). They calculated the I2 statistic to assess heterogeneity across studies, where an I2 of less than 25% indicates a small amount of inconsistency, and greater than 50% indicates a large amount of inconsistency.
Together, overweight and obesity were associated with an OR of 1.38 (95% CI, 1.06-1.8) for cardiotoxicity, with an I2 of 43%, suggesting moderate heterogeneity.
Being obese (OR = 1.47; 95% CI, 0.95-2.28; I2 = 47%) or overweight (OR = 1.15; 95% CI, 0.83-1.58; I2 = 27%) also each increased the risk for cardiotoxicity. These associations appeared to occur independently of study design; year of publication; drug regimen; and definitions of cardiotoxicity, overweight and obesity.
Results of a network meta-analyses showed the risk for cardiotoxicity increased as BMI increased (P = .05). The risk was lowest for overweight patients (OR vs. normal-weight patients = 1.13; 95% CI, 0.8-1.61) and highest for obese patients (OR vs. normal-weight patients = 1.44; 95% CI, 0.99-2.1).
Researchers acknowledged they were unable to adjust for other classic risk factors of anthracycline and trastuzumab cardiotoxicity. Also, most of the studies were not designed to address obesity as a risk factor, which could lead to bias in data collection.
“Our data confirmed our hypothesis, and the associations we described between obesity and cardiotoxicity were independent of the study design, year of publication, drug regimen (anthracyclines alone vs. sequential anthracyclines and trastuzumab) or definitions of cardiotoxicity and of overweight/obesity,” Guenancia told HemOnc Today. “It will be crucial to identify the mechanisms and the molecules involved in the interaction between obesity and the heart leading to a higher likelihood to heart failure after anthracyclines and trastuzumab.” – by Nick Andrews
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Charles Guenancia, MD, PhD, can be reached at: charles.guenancia@chu-dijon.fr.
Disclosure: Guenancia reports travel accommodations and expense from Biotronik International, Boston Scientific, LivaNova, Medtronic and St. Jude Medical. One other researcher reports consultant/advisory roles with and research funding from Astella Pharma, AstraZeneca, Bristol-Myers Squibb, Clovis Oncology and Incyte.
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