Evolution in the treatment of advanced breast cancer

There has been a gradual evolution in the philosophy of treatment for metastatic breast cancer. It has long been known that endocrine therapy, radiotherapy, and chemotherapy could offer substantial palliative benefits to patients with symptomatic metastases. While these quality of life issues remain crucially important, it is increasingly recognized that the survival of patients with this condition also appears to be improving as a result of therapeutic advances. Chemotherapy appears to prolong the median duration of survival of patients, probably by approximately 1 year. It is the common experience of oncologists that patients with life-threatening visceral metastases may be rescued with chemotherapy. Until recently, doxorubicin was considered to be the most active single agent available for the treatment of metastatic breast cancer, with response rates of 40% to 50% commonly reported. Other active agents include cisplatin, cyclophosphamide, 5-fluorouracil, ifosfamide, methotrexate, mitomycin-C, mitoxantrone, vinblastine, and vincristine. Anthracycline-containing regimens were found to be more effective than combinations without anthracyclines, but overall, it is not clear whether combinations are superior to high-dose single-agent anthracyclines. Since the development of the cyclophosphamide/doxorubicin/5-fluorouracil regimen, no major improvements on combination regimens have been achieved until the discovery of the taxoids. These new agents have substantial activity against metastatic breast cancer. The results of phase II studies suggest that of these agents, used at the recommended doses, docetaxel (Taxotere, Rhône-Poulenc Rorer, Antony, France) may be the most active, achieving an objective response rate of 59% in minimally pretreated patients and 47% when used in second-line treatment. In these studies, docetaxel was given at the standard dose of 100 mg/m2 over 1 hour. Recent results from phase III studies in which individual studies with docetaxel and paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) have been compared with standard therapies indicate that docetaxel is the most active single agent in metastatic breast cancer.