Stage IV breast cancer (metastatic foci beyond the axillary lymph nodes) initially may respond well to systemic salvage therapy with hormonal or chemotherapy drugs. Hormonal therapy is preferred because of its lower toxicity. Patients who eventually relapse after response to first-line hormone therapy may benefit from different hormonal treatments, but the probability (and duration) of response declines with each episode of progression. Chemotherapy is a rational option for patients whose cancers are hormone resistant, for those whose tumors lack hormone receptors, and for those who have rapidly growing visceral tumors. Doxorubicin achieves the highest response rates among the commonly used chemotherapy drugs, but cumulative doses above 500 mg/m2 may cause cardiomyopathy. Of the newer agents, paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) has been approved for use in anthracycline-resistant disease. Randomized trials have shown that increasing the dose intensity (ie, the amount of drug delivered per unit of time) overcomes some drug resistance. Most regimens used to treat stage IV disease are variations of the standard cyclophosphamide/methotrexate/5-fluorouracil (CMF) and cyclophosphamide/doxorubicin/5-fluorouracil (CAF) combinations. Single-agent treatment with doxorubicin or paclitaxel at maximum dose intensities produces response rates comparable with the best combination treatments. The use of untested drug combinations is regrettable and should be avoided. The specific treatment goal in responding patients (to reduce cancer symptoms or to reduce chemotherapy-related toxicity) should determine the need for continuous or intermittent drug administration. When first-line chemotherapy fails, a variety of single agents and combinations may be used, including paclitaxel, mitomycin/vinblastine, 5-fluorouracil, and cisplatin with etoposide or another agent. Future investigations should focus on the possibility of high complete response rates in ideal candidates using regimens that consist of very high chemotherapy doses with hematopoietic support or on new therapies that disrupt some step in the cellular processes of breast cancer.
