Combination adjuvant chemotherapy for node-positive breast cancer. Inadequacy of a single perioperative cycle.

We studied the timing and duration of adjuvant chemotherapy for operable breast cancer with axillary-node involvement in a randomized trial including 1229 patients divided into three treatment groups. One group received a single perioperative course of adjuvant combination chemotherapy beginning within 36 hours of mastectomy; a second received six cycles of conventionally timed adjuvant chemotherapy starting 25 to 32 days after operation; and a third received both the perioperative cycle and the conventionally timed regimen. The chemotherapy consisted of cyclophosphamide, methotrexate, and fluorouracil. Tamoxifen was added to the conventionally timed regimen in postmenopausal women. At a median follow-up of 42 months, the estimated four-year disease-free survival was 40 percent for the single perioperative cycle, 62 percent for the longer, conventionally timed regimen, and 60 percent for the combined program (P less than 0.0001). Overall survival differences also favored the longer treatments (P = 0.011). We conclude that a single perioperative cycle of adjuvant combination chemotherapy is less effective than prolonged therapy in patients with operable breast cancer and involved axillary nodes. Furthermore, starting the prolonged therapy perioperatively is no more effective than starting treatment four weeks after mastectomy.