Locoregional recurrence is a harbinger of disseminated disease, and historically the estimated 5-year survival when treated with local therapy only varies between 21% and 37%. The role of systemic treatment after local treatment is unclear at present. The authors investigated the results of systemic chemotherapy for these patients after complete local surgical resection. Data on 80 patients were evaluable for toxicity, time to treatment failure (TTF), and survival. Sixty-four patients received doxorubicin-based treatments, four received methotrexate-based combinations, and 12 received tamoxifen only. Among the 68 patients treated with cytostatics, there were two possible treatment-related deaths. Two patients developed grade 3 neutropenia, four developed grade 3 vomiting, and 42 had grade 2 toxicity. The 2- and 5-year disease free survival at a mean follow-up period of 5.5 years were 56% and 38%, respectively. The projected median TTF was 32 months (95% confidence interval, 23-82). Two- and 5-year overall survival were 86% and 62%, respectively, with a projected median survival of 93 months (7.75 years; 95% confidence interval, 64-177). These results show systemic therapy improved TTF and survival for patients with stage IV, no-evidence-of-disease breast cancer. Randomized studies are needed to confirm these findings and define optimal therapy.