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ABSTRACT: The best management of large, diffuse or inflammatory breast cancers is uncertain and the place of radiotherapy and/or surgery is not clearly defined. A cohort of 123 patients with non-metastatic locally advanced or inflammatory breast cancer 3 cm or more in diameter or T4, was treated between 1989 and 2006. All patients received primary chemotherapy followed by radiotherapy, 40 Gy in 15 fractions with 10 Gy boost. Patients with ER positive tumours received Tamoxifen. Assessment was carried out 8 weeks post-treatment and surgery was reserved for residual or recurrent disease. For each stage there were T2/3: 63, T4b: 31 and T4d: 29 patients. 80 had complete clinical response (65%) but 18 patients were never free of inoperable local disease. 25 patients had residual operable disease at assessment and 12 patients who initially had a complete response developed operable local recurrence (LR). 37 Patients (30%) had surgery at a mean of 15 months post diagnosis. At 5 years, overall survival (OS) of the two surgical groups was not significantly different from those 68 patients who had complete remission without surgery, p=0.218, HR 1.46 (0.80-2.55). Surgery as an independent variable to predict survival was not significant on a Cox proportional hazards model (p=0.97). LR in the surgical groups was 13.5% vs 17.5% in the non-surgical patients. The median OS was 64.5 months and disease-free survival (DFS) was 52.5 months. 5-Year OS was 54% and DFS survival 43%. In patients with a complete or partial response to chemo-radiotherapy for locally advanced or inflammatory breast cancer, reserving surgery for those with residual or recurrent local disease did not appear to compromise survival. This finding would support examination of this treatment strategy by a randomised controlled trial.