Incidence and identification of risk factors for trastuzumab-induced cardiotoxicity in breast cancer patients: an audit of a single “real-world” setting

Abstract

Management of human epidermal growth factor receptor-2-positive (HER2+) breast cancer patients includes the combination of adjuvant chemotherapy and trastuzumab. A meta-analysis reported that <5% of HER2+ breast cancer patients will develop trastuzumab-induced cardiotoxicity (TIC). Observational data suggest that incidence is much higher. We aimed to determine the incidence, time to development, and risk factors associated with TIC among less selected patients. A retrospective cohort study was carried out in 160 HER2+ breast cancer patients who received adjuvant chemotherapy with trastuzumab from January 2006 to June 2014 at St. Michael's Hospital, Toronto, Canada. Patient demographics, cardiovascular history, and TIC were recorded. TIC was defined as symptomatic (heart failure) or asymptomatic [decline in left ventricular ejection fraction (LVEF) by ≥10% or LVEF ≤ 50%]. Of the 160 patients [median age 52 (IQR 45-60), 48.1% on anthracycline-based chemotherapy], 34 patients (21.3%) experienced TIC (median follow-up 55.4 months). The median time to development of TIC was 28.5 weeks during trastuzumab therapy. Those with TIC were more likely to have undergone a mastectomy (52.9 vs. 33.3%, p = 0.04). However, after adjusting for anthracycline-based chemotherapy, and radiotherapy, mastectomy was not independently associated with TIC (HR 2.02; 95% CI 0.88-4.63). The incidence of TIC is higher in our "real-world" population compared to clinical trial data. The median time to development of TIC was 28 weeks after trastuzumab initiation, approximately the 10th treatment of trastuzumab. Timely identification and management of patients is important to avoid irreversible cardiac toxicity and improve breast cancer survival.

Risk factors associated with trastuzumab-induced cardiotoxicity in patients with human epidermal growth factor receptor 2-positive breast cancer

“…This study has recognized a number of factors associated with significant increases in TIC, including tumor site (unilateral vs. bilateral), breast surgery, and concomitant taxane chemotherapy. Other studies have reported a diverse number of risk factors that include elderly age,[21] African ethnicity,[22] overweight,[23] mastectomy surgery,[24] concurrent anthracyclines,[25] baseline LVEF value,[26] underlying cardiac conditions,[27] and diabetes. [28]…”

A closer look at immune-mediated myocarditis in the era of combined checkpoint blockade and targeted therapies

“…The incidence of immune-mediated myocarditis is possibly underreported in clinical trials given cardiac assessments were not routinely performed and trial patients may have less comorbidities. Emerging evidence suggests that the real-world rates of cardiotoxicity is higher than previously reported [12,22].…”

Prevention, Detection, and Management of Heart Failure in Patients Treated for Breast Cancer

“…In the clinical setting trastuzumab-induced myocardial dysfunction is potentiated by prior treatment with anthracyclines, which is also supported by preclinical studies [34][35][36][37]. Other risk factors include age > 65 years, high body mass index > 30 kg/m 2 , hypertension, and lower LVEF at baseline, while there are still conflicting data on other cardiovascular risk factors as diabetes, coronary artery disease, valvular dysfunction, and left ventricular hypertrophy [34,38]. Trastuzumab-induced left ventricular dysfunction is to some extent reversible when paused or discontinued [10,[39][40][41].…”