title: Influence of chemotherapy on EGFR mutation status among patients with non-small-cell lung cancer.
abstract: OBJECTIVE
  EGFR mutation is a predictor of epidermal growth factor receptor-tyrosine kinase inhibitor treatment response in patients with non-small-cell lung cancer (NSCLC). However, it remains unclear whether chemotherapy affects EGFR mutation status in NSCLC. We investigated the influence of chemotherapy on EGFR mutations in plasma and tumor tissues from patients with NSCLC.
  
  
  METHODS
  Samples were derived from three cohorts: one, 264 patients with advanced NSCLC who received first-line chemotherapy with matched pre- and postchemotherapy blood samples; two, 63 patients with stages IIb to IIIb disease with pre- and post-neoadjuvant chemotherapy tumor tissues; and three, 79 patients with advanced NSCLC who underwent palliative surgery. EGFR mutation status was determined and analyzed to reveal potential impact of chemotherapy.
  
  
  RESULTS
  In the first cohort, EGFR mutations were detected in 34.5% of the prechemotherapy plasma samples (91 of 264) but in only 23.1% of the postchemotherapy plasma samples (61 of 264). The decrease in EGFR mutation rate was statistically significant (P < .001). Patients whose EGFR mutations switched from positive to negative after chemotherapy had a better partial response (PR) than patients with a reverse change (P = .037). A similar decrease in EGFR mutation rate was observed in tissues after neoadjuvant chemotherapy in the second cohort (34.9% [22 of 63] v 19.0% [12 of 63]; P = .013). In the third cohort, 38.0% of the tumors (30 of 79) showed an intratumor heterogeneity of EGFR mutation, whereas 62.0% (49 of 79) were homogeneous, either with EGFR mutation or no mutation.
  
  
  CONCLUSIONS
  Our results suggest that chemotherapy may reduce EGFR mutation frequency in patients with NSCLC, likely the result of a preferential response of subclones with EGFR mutations in tumors with heterogeneous tumor cell populations.
authors: Peking University Cancer Hospital and Institute, Beijing, China.
authors: Hua
authors: H
authors: Bai
authors: Zhijie
authors: Z
authors: Wang
authors: Keneng
authors: K
authors: Chen
authors: Jun
authors: J
authors: Zhao
authors: J Jack
authors: JJ
authors: Lee
authors: Shuhang
authors: S
authors: Wang
authors: Qinghua
authors: Q
authors: Zhou
authors: Minglei
authors: M
authors: Zhuo
authors: Li
authors: L
authors: Mao
authors: Tongtong
authors: T
authors: An
authors: Jianchun
authors: J
authors: Duan
authors: Lu
authors: L
authors: Yang
authors: Meina
authors: M
authors: Wu
authors: Zhen
authors: Z
authors: Liang
authors: Yuyan
authors: Y
authors: Wang
authors: Xiaozheng
authors: X
authors: Kang
authors: Jie
authors: J
authors: Wang
mesh_terms: D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000097:blood / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D017024:Chemotherapy, Adjuvant; D016009:Chi-Square Distribution; D002681:China; D015331:Cohort Studies; D004273:DNA, Neoplasm / Q000097:blood*; D066246:ErbB Receptors / Q000037:antagonists & inhibitors* / Q000235:genetics*; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D020022:Genetic Predisposition to Disease; D006801:Humans; D008175:Lung Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000187:drug effects*; D020360:Neoadjuvant Therapy; D009367:Neoplasm Staging; D010166:Palliative Care; D010641:Phenotype; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage; D018570:Risk Assessment; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D004273:DNA, Neoplasm; D047428:Protein Kinase Inhibitors; C512478:EGFR protein, human; D066246:ErbB Receptors