Trastuzumab adjuvant chemotherapy and cardiotoxicity in real-world women with breast cancer

Abstract

Background: Adjuvant trastuzumab therapy improves survival of human epidermal growth factor receptor 2 (HER2)-positive women with early breast cancer (EBC). A careful monitoring of cardiac function is needed due to potential trastuzumab cardiotoxicity (Tcardiotox). To date, the incidence, timing, and phenotype of patients with Tcardiotox in clinical practice are not well known.

Methods and results: A total of 499 consecutive HER2-positive women (mean age 55 ± 11 years) with EBC treated with trastuzumab between January 2008 and June 2009 at 10 Italian institutions were followed for 1 year. We evaluated incidence, time of occurrence, and clinical features associated with Tcardiotox. Left ventricular ejection fraction (LVEF) was evaluated by echocardiography at baseline and at 3, 6, 9, and 12 months during trastuzumab therapy. Tcardiotox was recognized in 133 patients (27%): 102 (20%) showed asymptomatic reduction in LVEF of >10% but ≤20% (grade 1 Tcardiotox); 15 (3%) had asymptomatic decline of LVEF of >20% or <50% (grade 2); and 16 (3%) had symptomatic heart failure (grade 3). Trastuzumab was discontinued due to cardiotoxicity in 24 patients (5%) and restarted in 13 after LVEF recovery. Forty-one percent of Tcardiotox cases occurred within the first 3 months of follow-up, most prevalently in older patients with higher creatinine levels and in patients pretreated with doxorubicin and radiotherapy.

Conclusions: In clinical practice, Tcardiotox is frequent in HER2-positive women with EBC and occurs in the first 3 months of therapy. Cardiac dysfunction is mild and asymptomatic in the majority of patients. The interruption of treatment is a rare event which occurs, however, in a significantly higher percentage than reported in randomized clinical trials.