Predictors of late-onset heart failure in breast cancer patients treated with doxorubicin

Anthracyclines are an integral component of breast cancer chemotherapy. They exert many cardiotoxic effects, including heart failure. The onset of anthracycline-induced heart failure (AIHF) can occur years after completion of chemotherapy and incurs significant morbidity and mortality. Few studies have attempted to characterize risk factors for its development. Our purpose was to determine the incidence of early and late AIHF in breast cancer survivors and to identify factors that increase the risk for late-onset AIHF. Patients with invasive breast cancer who received doxorubicin-containing chemotherapy at University Hospitals Case Medical Center from 1998 to 2006 were included. Medical history and tumor and treatment characteristics were abstracted from medical records. Patients who developed heart failure were compared to those who did not and were also stratified based on timing of heart failure. One thousand one hundred fifty-three patients received doxorubicin-based chemotherapy for invasive breast cancer with an average follow-up of 7.6 years (standard deviation (SD) = 3.4). The overall incidence of heart failure was 10.4, with a 2.9 and 7.6 % incidence of early- and late-onset heart failure, respectively. Human epidermal growth factor receptor 2 (HER2) status, hypertension, and coronary artery disease were significant predictors for both heart failure groups (p < 0.001). Type II diabetes was a risk factor for the late-onset AIHF group (p < 0.001). HER2 status and cardiovascular risk factors increased the risk of heart failure among doxorubicin users. Patients with type II diabetes were at increased risk of late-onset AIHF. We identified at risk survivors who may benefit from prolonged monitoring and/or early intervention.