Intratumor heterogeneity and chemotherapy-induced changes in EGFR status in non-small cell lung cancer.

INTRODUCTION: Biomarker expression is increasingly being used to customize treatment in non-small cell lung cancer (NSCLC). The choice of systemic treatment usually depends on biomarker expression in the initial diagnostic biopsy taken before initiation of first-line treatment. Chemotherapy induces DNA damages in the tumor cells, and thus, biomarker expression in the tumor after systemic treatment might not be identical to biomarker expression in the diagnostic biopsy. NSCLC is highly heterogeneous and biomarker expression may vary in different areas within the same tumor. This review explores the tumor heterogeneity and chemotherapy-induced changes in EGFR biomarker status in NSCLC.
METHODS: A literature search was performed in August 2011 using pubmed.
RESULTS: Fifteen trials explored EGFR status in primary tumor and subsequent resected primary tumor, lymph node metastases, or organ metastases. Four papers compared EGFR status in primary tumor or metastases before and after systemic treatment. All trials included relatively few patients and used different chemotherapy regimes, biopsy locations, or time intervals between biopsies.
CONCLUSIONS: Tumor heterogeneity and probably also previous systemic treatment may be an obstacle for correct interpretation of EGFR status in NSCLC. Heterogeneity regarding EGFR mutations is probably rare and previously reported intra and intertumor heterogeneity may be due to methodological issues. In the current and future clinical scenario with many different options for systemic treatment both as 2nd line and beyond, it is increasingly important to further elucidate the role extent of chemotherapy-induced changes in biomarker expression for proper use of biomarkers in order to customize treatment and thus improve prognosis.