Effect of Obesity, Dyslipidemia, and Diabetes on Trastuzumab-related Cardiotoxicity in Breast Cancer

Abstract

Background Clinical trials have demonstrated an increased risk of cardiotoxicity in patients with breast cancer (bca) receiving trastuzumab-based therapy. Diabetes, dyslipidemia, and obesity are known risk factors for cardiovascular disease. Studies have yielded conflicting results about whether those factors increase the risk of cardiotoxicity in patients with bca receiving trastuzumab.Methods In this retrospective cohort study, data were collected for 243 patients with bca positive for her2 (the human epidermal growth factor receptor 2) who were receiving trastuzumab and who were referred to The Ottawa Hospital Cardio-oncology Referral Clinic between 2008 and 2013. The data collected included patient demographics, reason for referral, cardiac function, chemotherapy regimen (including anthracycline use), and 3 comorbidities (diabetes, dyslipidemia, obesity). Rates of symptomatic cancer treatment–related cardiac dysfunction (sctcd) and asymptomatic decline in left ventricular ejection fraction (adlvef) were calculated for patients with and without the comorbidities of interest.Results Of the 243 identified patients, 104 had either diabetes, dyslipidemia, or obesity. In that population, the most likely reason for referral to the cardio-oncology clinic was adlvef. The combination of 2 or 3 comorbidities significantly increased the incidence of sctcd in our population, reaching a rate of 67% for patients with obesity and dyslipidemia [relative risk (rr): 2.2; p = 0.04], 69% for patients with obesity and diabetes (rr: 2.3; p = 0.02), and 72% for patients with all 3 risk factors (rr: 2.4; p = 0.08).Conclusions The combination of 2 or 3 comorbidities significantly increases the incidence of symptomatic cancer treatment–related cardiotoxicity. Patients with bca experiencing cancer treatment–related cardiotoxicity who have a history of diabetes, dyslipidemia, and obesity might require more proactive strategies for prevention, detection, and treatment of cardiotoxicity while receiving trastuzumab-based treatment.

Delta NT-proBNP predicts cardiotoxicity in HER2-positive breast cancer patients treated with trastuzumab

“…Since TIC patients often had more than one risk factor for cardiovascular disease and the number of TIC patients were only six we cannot define which of the identified risk factors that were correlated with development of TIC, since the power to do a multinominal logistic regression analysis was too low. However, our findings are in line with previous studies showing that TIC more often develops in older women with cardiovascular risk factors [6,23]. Furthermore, women in the TIC group had a lower LVEF than women in the control group at baseline indicating that women with lower LVEF may be at risk for developing TIC.…”

Onco-Cardiology: Consensus Paper of the German Cardiac Society, the German Society for Pediatric Cardiology and Congenital Heart Defects and the German Society for Hematology and Medical Oncology

“…Cardiovascular disease and cancer not only share common mechanisms such as chronic inflammation but also exhibit common risk factors [ 47 , 90 ]. Diabetes mellitus, obesity and hypercholesterolaemia are not only considered to be risk factors for breast cancer but also are associated with increased cardiovascular side effects [ 67 , 101 ]. Although the reduced cardiotoxicity observed in a retrospective study of breast cancer patients treated with statins needs to be confirmed in prospective studies [ 17 ], we consider the treatment of hypercholesterolaemia to be useful.…”

Cardiovascular risk management in cancer survivors: Are we doing it right?

“…Recent data suggest that diabetic risk reduction among cancer survivors was much lower compared to their non-cancer counterparts[ 17 ]. Uncontrolled diabetes, obesity, and hyperlipidemia have been shown to induce myocardial fibrosis which subsequently increases the incidence of symptomatic cancer treatment-related cardiotoxicity[ 18 ]. Hence, increased vigilance and multi-disciplinary collaborations between expert diabetic educator, a nutritionist and/or dietician, and primary care physicians are required for optimal diabetes management and maintaining the HbA1c goal of < 7% in most patients.…”