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Potential Link Between Obesity and Cardiotoxicity From Anthracyclines Alone or With Trastuzumab for Breast Cancer

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Key Points

  • Obesity and overweight were associated with an increased risk of cardiotoxicity in women receiving treatment with anthracyclines and sequential anthracyclines/trastuzumab for breast cancer.
  • A nonsignificantly increased risk was observed for obesity alone and overweight alone.

Obesity and being overweight were associated with an increased risk of cardiotoxicity in women receiving treatment with anthracyclines and sequential anthracyclines/trastuzumab (Herceptin) for breast cancer, according to a systematic review and meta-analysis reported in the Journal of Clinical Oncology by Guenancia et al.

The analysis, which was not a patient-level meta-analysis, did not account for the potential contributions of obesity-related cardiovascular risk factors to drug-associated cardiotoxicity. The specific cardiotoxicity risk with trastuzumab alone could not be assessed without individual data, since all of the studies that included trastuzumab included a proportion of patients who also received anthracycline treatment.

Study Details

The analysis included 15 studies with 8,745 patients treated with anthracyclines or sequential anthracyclines and trastuzumab. A random-effects analysis and network meta-analysis were performed, and publication bias was assessed. Heterogeneity across studies was measured by I2 statistic, with larger values indicting greater inconsistency.

Increased Risk of Cardiotoxicity

The combination of obesity and overweight (body mass index > 25 kg/m2) was associated with an increased risk of cardiotoxicity after anthracycline or sequential anthracycline/trastuzumab treatment: Pooled odds ratios for cardiotoxicity were 1.38 (95% confidence interval [CI] = 1.06–1.80, I2 = 43% [moderate heterogeneity]) for overweight or obesity; 1.47 (95% CI = 0.95–2.28, I2 = 47%) for obesity; and 1.15 (95% CI = 0.83–1.58, I2 = 27% [low heterogeneity]) for overweight. The associations were independent of study design, year of publication, drug regimen (anthracycline alone vs sequential anthracycline/trastuzumab), or definitions of cardiotoxicity or overweight and obesity.

As noted by the investigators: “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.” They concluded: “Our findings in a largely unadjusted analysis suggest that overweight and obesity are risk factors for cardiotoxicity from anthracyclines and sequential anthracyclines and trastuzumab.”

Charles Guenancia, MD, PhD, of Dijon University Hospital Center, is the corresponding author of the Journal of Clinical Oncology article.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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