Randomized multicenter 2 x 2-factorial design study of chemo/endocrine therapy in operable, node-positive breast cancer (protocol 2).

In 1984, the West German Breast Cancer Study Group (see Appendix A) set up a controlled clinical trial on adjuvant therapy in “early” breast cancer to answer the following question: Is it possible to reduce six cycles of cyclophosphamide, methotrexate, and 5-fluorouracil (CMF), to be given within 6 months starting perioperatively, to half the dose within half the time without decreasing the patient’s chance of survival? At that time, we started out from the following assumptions: 1. Polychemotherapy is superior to monotherapy (Fisher et al. 1981). 2. No other drug combination has so far been proved superior to the modified Bonadonna scheme (Bonadonna et al. 1981). 3. Twelve cycles of CMF can safely be reduced to six cycles (Bonadonna et al. 1981). 4. Early onset of adjuvant systemic chemotherapy is important: “Small is sensitive” (Nissen-Meyer 1982; Shackney et al. 1978). 5. Prolonged chemotherapy might be for the benefit of a small group of patients only, and therefore costs and benefits of cytotoxic chemotherapy in terms of side effects and gains in survival time should be taken into account.