Conversion from Positive to Negative EGFR Mutation due to Clonal Selection during Long-Term Treatment with Epidermal Growth Factor Receptor-Tyrosine Kinase Inhibitors: A Case Report.

A 77-year-old woman with postoperative recurrent non-small cell lung adenocarcinoma, which exhibited an epidermal growth factor receptor (EGFR) L858R mutation, was treated with gefitinib and erlotinib. Seven years after the start of treatment, the patient experienced a recurrence of malignant pleural effusion. However, 3 different genetic tests revealed that the lung adenocarcinoma cells in the pleural effusion had lost EGFR L858R mutation, suggesting that long-term treatment with EGFR-tyrosine kinase inhibitors (TKIs) converted EGFR mutation from positive to negative. The negative conversion of EGFR mutation as a mechanism of acquired resistance to EGFR-TKIs is considered rare and needs to be further investigated.