Treatment of anthracycline-resistant breast cancer

The anthracyclines are commonly used for the treatment of early stage and advanced stage breast cancer, but many patients develop resistance to therapy. The definition of anthracycline resistance varies considerably in the literature, but in most cases includes disease progression during or within 6-12 months after completion of anthracycline therapy. Some authors have distinguished true anthracycline resistance (defined as progression during anthracycline therapy) from anthracycline pretreatment (defined as progression after completion of therapy). Single agents that have demonstrated response rates of at least 15-20% in anthracycline pretreated or resistant disease include the antitubulin agents (docetaxel, paclitaxel, vinorelbine), antimetabolites (capecitabine, fluorouracil), nucleoside analogues (gemcitabine), and trastuzumab (for HER2/neu positive disease only). Phase III studies have demonstrated that docetaxel is more effective than paclitaxel, mitomycin/vinblastine, and methotrexate/fluorouracil, and that the docetaxel/capecitabine combination is more effective than docetaxel alone. The decision regarding which agent(s) to use should be based upon the patient's prior treatment history, tumor biology (HER2/neu and hormone receptor expression), comorbid conditions (e.g. neuropathy, heart disease), and other considerations (e.g. insurance coverage for oral medication). The choice of a specific treatment regimen must be individualized based upon these considerations.