Background
Patients with early-stage breast cancer who are at substantial risk for systemic metastases are increasingly treated with breast-conserving therapy and adjuvant chemotherapy. However, the optimal sequencing of chemotherapy and radiation therapy is not clear.

Methods
Two hundred forty-four patients with stage I or II breast cancer who were at substantial risk for distant metastases were randomly assigned to receive a 12- week course of chemotherapy either before or after radiation therapy. All had had breast-conserving surgery. The median length of follow-up in surviving patients was 58 months (range, 10 to 124).

Results
The five-year actuarial rates of cancer recurrence at any site and of distant metastases in the radiotherapy- first group and the chemotherapy-first group were38 percent and 31 percent (P=0.17) and 36 percent and 25 percent (P=0.05), respectively. Overall survival was 73 percent and 81 percent (P=0.11), respectively. The five-year crude rates of first recurrence according to site in the radiotherapy-first and chemotherapy-first groups, respectively, were 5 percent and 14 percent for local recurrence and 32 percent and 20 percent for distant or regional recurrence or both. This difference in the pattern of recurrence was of borderline statistical significance (P=0.07).

Conclusions
This study suggests that for patients at substantial risk for systemic etastases, it is preferable to give a 12-week course of chemotherapy followed by radiation therapy, rather than radiation therapy followed by chemotherapy. (N Engl J Med 1996;334:1356-61.)