Anthracycline-Resistant Breast Cancer

The management of breast cancer requires the judicious use of cytotoxic therapy, hormone therapy, radiotherapy, analgesics, and other forms of physical and psychological support for optimal palliation of symptoms and prolongation of survival. Patients with low-risk metastatic breast cancer often benefit from hormone therapy as initial management; other patients are best treated with early introduction of cytotoxic therapy. Combination chemotherapy is superior to single-agent treatment, and anthracycline-containing regimens are more effective than the rest. The development of primary or secondary resistance to anthracycline therapy represents an adverse prognostic indicator, associated, until recently, with poor response to subsequent cytotoxic therapy and short survival. Prior to the development of taxanes, response to second- and third-line chemotherapy for patients with primary anthracycline resistance was observed in 5% of patients. Paclitaxel and docetaxel retain substantial antitumor activity in anthracycline-resistant breast cancer, and vinorelbine is also moderately effective in this subset of patients. Attempts to reverse P-glycoprotein-related drug resistance, while encouraging in the laboratory, have not been successful in the clinic. A number of novel therapeutic interventions, many that bypass traditional mechanisms of drug resistance, are currently in clinical developments, with encouraging preliminary results.