Metastatic breast cancer: the role of pegylated liposomal doxorubicin after conventional anthracyclines.

Anthracyclines demonstrate significant disease activity in breast cancer and are a key component of therapy in both early and advanced disease. It has been long recognized that these agents are associated with cumulative dose-related cardiotoxicity that often limits their utility at the time of disease recurrence. The risk of anthracycline-associated cardiotoxicity appears to be highest in women with HER2-overexpressing breast cancer previously having received an adjuvant anthracycline-trastuzumab regimen. Clinical trials have demonstrated that pegylated liposomal doxorubicin (PLD) is equally active but associated with a significantly lower risk of cardiotoxicity compared with conventional doxorubicin whether administered as monotherapy or in combination with trastuzumab. Thus, PLD can be effectively and safely substituted for conventional doxorubicin, allowing retreatment with an anthracycline in the metastatic setting. PLD has also been shown to improve time to tumor progression when used as maintenance therapy. These data, when coupled with the need to maintain efficacy and reduce cardiotoxicity in the management of metastatic breast cancer, support the use of PLD in the metastatic setting, as well as support the rationale for evaluating PLD as adjuvant therapy.