Systemic therapy of advanced breast cancer

Many cytotoxic agents have demonstrated activity in advanced breast cancer, the more active agents being cyclophosphamide and the anthracyclines doxorubicin and epirubicin. Combinations of drugs are generally superior to single agents in terms of response rate, duration of response and survival. The treatment of advanced breast cancer can be continued either until treatment failure, or for a limited time from either initiation of therapy or from the observation of complete response. Although these are issues of significant concern, data from randomised trials are limited, and so the question of optimal treatment duration remains open. Randomised trials comparing regimens that differ by a dose intensity factor of less than 2 have failed to demonstrate significant differences in efficacy between the dose levels. With higher doses, as applied in combination with colony-stimulating factors and bone marrow transplantation, response rates seem to increase, but whether this translates into improved survival has not yet been answered by the results of randomised trials. Approximately 30% of patients respond to endocrine therapy. From the results of randomised trials, which have compared the efficacies and toxicities of different endocrine modalities including combined endocrine therapy, single-agent tamoxifen is generally considered as the preferred first-line treatment, leaving progestins and aromatase inhibitors as alternatives for second-line endocrine therapy in responders. In the majority of trials, chemotherapy combined with endocrine therapy has given improved response rates compared with chemotherapy alone, but the differences have not generally been translated into prolonged survival with combined modalities. This gives rise to the question of the optimal sequence of chemotherapy and endocrine therapy, a subject needing further evaluation in future trials.