Chemotherapy of breast cancer: a historical perspective.

Over the last 30 years, our knowledge about the clinical behavior of breast cancer has increased substantially. Our ability to identify several prognostic subgroups and predict hormone-responsive and hormone-resistant disease has led to more rational utilization of endocrine and cytotoxic treatments. Breast cancer is sensitive to multiple cytotoxic compounds. It has been demonstrated that combination chemotherapy produces higher overall and complete remission rates than sequential single agents, and that doxorubicin-containing combinations are more effective than other regimens. The introduction of new cytotoxic agents, including the taxanes paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) and docetaxel, gemcitabine, anthrapyrazoles, thymidylate synthase inhibitors, antifols, and camptothecin analogues, has added substantially to our antitumor armamentarium. Combinations of new drugs with old agents have resulted in regimens of enhanced activity. A large number of randomized comparative trials will determine which combinations have the highest therapeutic ratio and need to be incorporated into the standard management of metastatic and high-risk primary breast cancer.