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Aim and Background: The aim of this study was to investigate the efficacy of postoperative locoregional radiotherapy in patients with T1-T2 breast cancer and four or more positive axillary lymph nodes submitted to mastectomy or breast-conserving surgery followed by standard-dose or high-dose adjuvant chemotherapy. The incidence of locoregional relapses and the survival correlated with the number of positive nodes were recorded for each treatment arm., Patients and Methods: From August 1992 to August 1999 86 breast cancer patients (median age, 54 years, T1-T2, N+ > or = 4) submitted to surgery were treated. Sixty-three patients received standard-dose chemotherapy while 23 patients with 10 or more positive nodes received high-dose chemotherapy. After four courses of standard-dose anthracycline-based chemotherapy peripheral blood stem cells were mobilized with cyclophosphamide (7 g/m2) and G-CSF (10-16 microg/kg/day/sc). High-dose chemotherapy consisted of etoposide 1000 mg/m2, thiotepa 500 mg/m2 and carboplatin 800 mg/m2. Hormone receptor-positive patients underwent hormone therapy. Following chemotherapy all 86 patients were given conventional radiotherapy to the breast or the chest wall and the supraclavicular fossa. The high-dose subgroup received radiotherapy to the internal mammary nodes +/- axilla., Results: The median follow-up from the start of radiotherapy was 36.5 months. Locoregional relapses occurred in nine patients (10.4%); in four of them they were isolated (4.6%). Local relapses were four (4.6%) and regional relapses six (6.9%). Twenty-five patients (29%) had distant metastases. The five-year and eight-year overall actuarial survival rates were 82.6% +/- 4.8 and 60.1% +/- 8.8, respectively. No statistical differences were found when the number of positive nodes or the type of treatment of N+ 10 patients was included in the analysis., Conclusions: Breast cancer patients with four or more positive axillary lymph nodes are at high risk of developing locoregional and distant relapses. The results reported here demonstrate the efficacy of radiotherapy in the reduction of locoregional failure; no differences in survival and locoregional control in relation to treatment arm and number of positive nodes were found.