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Background: Axillary recurrence after negative sentinel lymph node biopsy (SLNB) in patients with invasive breast carcinoma remains a concern. Previous investigations to identify prognostic factors for axillary recurrence identified that a disproportionate number of patients with an axillary recurrence after negative SLNB were not treated with external beam radiation therapy (EBRT) of the breast as part of initial treatment. This finding prompted a systematic review to test the hypothesis that EBRT to the breast reduces the risk of axillary recurrence after negative SLNB. Methods: A literature search was performed in PubMed, the Cochrane Library and the Spanish-language database LILACS to identify articles publishing data regarding follow-up of sentinel lymph node (SLN)-negative patients. Reports and articles lacking information on the initial treatment were excluded. Results: Forty-five articles were accepted for review. A total of 23 357 SLN-negative patients were identified with median follow-up ranging from 15 to 102 months. Some 18 878 patients were treated with EBRT to the breast as part of their initial treatment. One hundred and twenty-seven patients with an axillary recurrence were identified, of whom 73 had EBRT as part of their initial treatment. Meta-analysis showed that EBRT was associated with a lower rate of axillary recurrence (P < 0.001), but this finding was subject to heterogeneity. Conclusion: This review and meta-analysis showed that EBRT is associated with a significantly lower axillary recurrence rate after negative SLNB. [ABSTRACT FROM AUTHOR]