Cardiotoxic consequences of anthracycline-containing therapy in patients with breast cancer

Abstract

In women, breast cancer is the second most common form of cancer and the leading cause of death caused by malignancy. The anthracycline antibiotics are potent anti-tumor agents used in a wide spectrum of malignancies. They are part of the gold standard adjuvant therapy for breast cancer and in metastatic disease they provide significant increases in response rate, time to disease progression, and overall survival. The addition of trastuzumab augments the effects of anthracycline-based therapy in both the adjuvant and metastatic settings. The successful use of anthracyclines is, however, restricted by the risk of developing life-threatening congestive heart failure. This risk increases exponentially with cumulative dose, and is further augmented by the addition of trastuzumab. Studies have reported that 10% to 26% of patients administered cumulative anthracycline doses above those recommended (> or =500 mg/m2 for doxorubicin and 1,000 mg/m2 for epirubicin) develop congestive heart failure, and that more than 50% of patients administered these doses will experience measurable functional impairment months to years after the end of therapy. The susceptibility of patients to anthracycline-induced cardiotoxicity varies widely, with a dramatic increase with advancing age. The onset of clinical and subclinical cardiac damage is delayed and occurs more than 3 months after the cessation of treatment, indicating a crucial time for functional impairment to occur and highlighting the ineffectiveness of monitoring left ventricular ejection fraction as an endpoint during anthracycline therapy. Possible future treatment options for managing anthracycline-induced cardiotoxicity include agents such as dexrazoxane that prevent oxygen-free radical generation. Further investigation is required into the use of angiotensin-converting enzyme inhibitors to redress cardiac damage and new methods of identifying patients at high risk of congestive heart failure before cardiac damage has occurred.