What is the ideal duration of adjuvant therapy for primary breast cancer: are four cycles of cyclophosphamide and doxorubicin enough?

For 25 years we have known that adjuvant chemotherapy improves both disease-free and overall survival for many of our patients with primary breast cancer. We also know that these therapies have significant toxicities and are not always effective. We have therefore focused a great deal of effort into maximizing the effectiveness of adjuvant chemotherapy and defining just how much chemotherapy, with respect to both dose and duration, is necessary to achieve this maximum benefit. In our attempt to define these parameters through clinical trials, we have been faced with many options, and we may not yet have defined an optimal regimen of chemotherapy, or an optimal duration. Although many physicians in the United States consider four cycles of cyclophosphamide and doxorubicin as "standard of care" for patients with primary breast cancer, many feel that both choice of regimen and duration of treatment remain controversial. The reasons for this uncertainty and lack of clarity are complex, and they are addressed in this review.