Influence of chemotherapy on EGFR mutation status.

Lung cancer is the leading cause of cancer death in the world. The frequency of epidermal growth factor receptor (EGFR) mutations in non-small-cell lung cancer (NSCLC) has ranged from 5-30%, depending on the population studied. Lung cancer patients with tumor EGFR activating mutations have a more favorable prognosis than those without. With regard to second-line tyrosine kinase inhibitors (TKIs) following platinum-based chemotherapy, its tumor response rate was less than first-line TKIs in patients with EGFR mutations. The change of EGFR mutation status during disease course may partially explain the difference in the predictive value of EGFR mutation between first- and second-line TKIs treatment. First-line chemotherapy may have influence on status of EGFR mutations, and thus, EGFR mutation status collected from the initial specimens for diagnosis might be inadequate for predicting efficacy of EGFR-TKI treatment after first-line chemotherapy. Intratumoral heterogeneity in the initial single tumor biopsy specimen could also lead to misinterpretation of the tumor EGFR mutation status and difficulty in making precise treatment decision. Many investigators used plasma EGFR mutation obtained from peripheral blood samples to represent the post-chemotherapy EGFR mutation status. However, many studies revealed that plasma EGFR mutation could not completely represent EGFR mutation status in the tumor tissue. There could be many reasons for the change of EGFR mutation status after chemotherapy. Influence of chemotherapy on EGFR mutation status may be one of the explanations for this phenomenon. Intratumoral heterogeneity also plays an important role in diversity of tumor EGFR mutation status. Further studies will be necessary to explain the mechanisms of chemotherapy-induced EGFR mutation change.