Long-term results of a randomized trial on the sequencing of radiotherapy and chemotherapy in breast cancer.

OBJECTIVE: A prospective, phase III randomized study was undertaken to compare the outcomes of 2 different radiotherapy and chemotherapy sequences in conservatively treated patients with breast cancer. METHODS: Between January 1997 and November 2002, 206 patients operated of quadrantectomy and axillary dissection for breast cancer, candidates to receive adjuvant CMF chemotherapy (cyclophosphamide, methotrexate, and fluorouracil) were assigned to concurrent or sequential radiation treatment by using a balanced randomization method. Before randomization patients were stratified by tumor diameter, age, and lymph node status. The primary end point was the freedom from breast recurrence, and secondary end points were overall and disease-free survival. Overall outcomes were analyzed according to the intention-to-treat principle. RESULTS: All 206 patients enrolled and randomized in the trial were analyzed. The median follow-up was 111 months, with no patient lost for follow-up. No difference in 10-years breast recurrence-free, disease-free, metastasis-free, and overall survival rates was observed in the 2 treatment sequence groups. The Hazard Ratios, calculated for each prognostic factor, showed no difference in all outcomes between the 2 treatment sequences. CONCLUSIONS: No influence of the treatment sequence on long-term outcomes was observed in this trial. This finding suggests that to avoid an increased risk of distant recurrence or an excessive toxicity, radiation therapy may be delayed until after the end of the more, recently used, anthracycline-based chemotherapy without increasing the risk of breast recurrences, thus allowing the delivery of full-dose chemotherapy in patients at risk for systemic disease spread.