Obesity in Early-Stage Breast Cancer May Increase Risk for Cardiotoxicity

Obese patients with early-stage breast cancer treated with anthracyclines and/or trastuzamab (Herceptin) may be at a higher risk of experiencing drops in left ventricular ejection fraction (LVEF), according to a study published in PLOS Medicine. 

Researchers suggested that these results should encourage further research into the mechanisms linking obesity to cardiotoxicity, and personalized risk assessment for cardiac complications following cardiotoxic therapies could offer several possible benefits for patients.

“These results highlight the higher prevalence of cardiovascular risk factors in these patients and the need to carefully assess cardiological background before any cardiotoxic drug prescription,” the authors wrote. “After multivariate analysis, among all cardiovascular risk factors, only obesity remained significantly associated with cardiotoxicity.” 

Using data collected from 2012-2014 in the French CANTO (CANcer TOXicities) study of 26 French cancer centers, researchers looked to examine the association of body mass index (BMI) and cardiotoxicity (defined as a reduction LEVF > 10 percentage point from baseline to LVEF < 50%). In this cohort of 929 patients with stage I-III breast cancer treated with anthracycline (86% epirubicin [Ellence], 7% doxorubicin [Lipodox]) and/or trastuzumab (36%), with LVEF at baseline, and at least 1 assessment post-chemotherapy, researchers analyzed associations between BMI and cardiotoxicity. 

At baseline, almost 50% of the study population was overweight or obese. During a mean follow-up of 22 ± 2 months following treatment completion, cardiotoxicity occurred in 29 patients (3.2%). Additionally, the obese group was found to be more prone to cardiotoxicity than the normal weight group (9/171 vs 8/466; P = 0.01). In multivariate analysis, obesity (odds ratio [OR] 3.02; 95% CI 1.10-8.25; P = 0.03) and administration of trastuzumab (OR 12.12; 95% CI, 3.6-40.4; P < 0.001) were independently associated with cardiotoxicity. 

“In light of our results, we suggest that future studies should specifically focus on overweight and obese patients,” the authors wrote. “Molecular pathways underlying the interaction between obesity and heart function, and leading to a higher probability of heart failure upon treatment with anthracyclines and trastuzumab, remain to be elucidated.”

Being obese was associated with a 3-fold increased risk of developing cardiotoxicity, regardless of other predictors, in this study. Almost half of the patients had a BMI > 25kg/m², indicating that overweight and obesity are frequently occurring risk factors for cardiotoxicity in patients with early breast cancer. 

“Our results show that overweight and obese patients would certainly benefit from careful cardiac screening and follow-up during and after chemotherapy,” the authors wrote.

Notably, researchers suggested that incidence of cardiotoxicity after chemotherapy agents may be increased by smoking or preexisting cardiovascular disease (CVD) (or individual patient genetic predisposition to CVD). Previously obtained data from larger cohorts have indicated that cancer survivors are significantly more prone to have cardiovascular risk factors such as overweight, hypertension, diabetes, and dyslipidemia compared with matched controls who did not have cancer. Moreover, a higher risk of CVD and CVD-related death in cancer survivors is probably a result of multiple factors, which may involve cardiotoxic effects of different cancer treatments, as well as comorbidities and unhealthy life-style habits. 

Cardiotoxicity is a serious side effect of both anthracyclines and trastuzumab, according to the researchers, potentially occurring even months to years after completion of cancer primary treatment. Cardiotoxicity, when presented, may severely impair the quality of life and overall survival of patients with breast cancer. Though exceptional progress has been made in the treatment of early disease, anthracyclines remain a key element of breast cancer therapy in combination with new-generation targeted drugs like trastuzumab. 

Reference:

Kaboré EG, Guenancia C, Vaz-Luis I, et al. Association of body mass index and cardiotoxicity related to anthracyclines and trastuzumab in early breast cancer: French CANTO cohort study. PLOS Medicine. doi:10.1371/journal.pmed/1002989.