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Background: Second primary malignancies (SPM) in the lung are not common in breast cancer (BC) patients. EGFR-mutant lung cancer (LC) is a separate molecular subset, and the coexistence of EGFR-mutant LC and BC has not been explored. We hypothesized that EGFR-mutant LC patients could have higher rates of primary BC than those with EGFR-wild type (WT). Methods: We collected data on clinical and molecular characteristics and outcomes of female patients with LC and a previous or simultaneous history of primary BC treated in our hospital from 2008 to 2014. Results: Data on treatment, follow-up, and EGFR mutation status were available for 356 patients. 17.7% (11/62) of patients with EGFR mutations had BC, compared to 1.02% (3/294) of EGFR-WT patients (p < 0.001). Both tumors were metachronous in 81.8%, with LC diagnosed 9 years after the diagnosis of BC. 5 of the 6 (83.3%) BC patients treated with radiotherapy developed LC in an area within the radiation field. No EGFR mutations were detected in BC tissue and no HER2 expression was detected in LC samples. Conclusion: SPM in the lung and breast occur more frequently among EGFR-mutant compared to EGFR-WT LC patients. Radiotherapy for BC may increase the risk of developing primary LC. (c) 2019 S. Karger AG, Basel