title: Epidermal growth factor receptor mutation testing in the care of lung cancer patients.
abstract: As the literature about epidermal growth factor receptor (EGFR) mutations grows and screening for mutations becomes increasingly integrated into clinical care, it is important to examine how best to do somatic mutational analyses and how best to use the test results in clinical decision making. We began offering mutation screening by comprehensive direct sequence analysis of exons 18 to 24 of the tyrosine kinase domain of EGFR in August 2004 as part of clinical cancer care and protocol therapy at our institutions. All identified potential mutations are confirmed with three to five independent PCRs of the original genomic DNA sample and, if not previously noted in the literature, are compared with the patient's germ-line DNA to ensure the finding is somatic. We formally analyzed the first 100 patients to undergo EGFR sequence analysis and found that testing was feasible and significantly affected the treatment of patients with non-small cell lung cancer (NSCLC). Patients harboring EGFR mutations were significantly more likely to receive recommendations for therapy with EGFR tyrosine kinase inhibitors (i.e., gefitinib or erlotinib) than patients without mutations. However, negative EGFR test results did not prevent physicians from administering these agents to selected patients. Ideally, a standardized technique for mutation testing could be developed, with demonstrated reproducibility and validity. Clinical trials incorporating molecular diagnostics are ongoing to assess the efficacy of EGFR tyrosine kinase inhibitors as first-line therapy for metastatic NSCLC and as adjuvant therapy for early-stage resected NSCLC. It is likely that mutation testing and other molecular analyses will be most useful in these two clinical situations.
authors.affiliation: Cancer Center and Department of Medicine, Massachusetts General Hospital, and Laboratory for Molecular Medicine, Harvard Medical School, Boston 02114, USA. LVSequist@Partners.org
authors.forename: Lecia V
authors.initials: LV
authors.lastname: Sequist
authors.forename: Victoria A
authors.initials: VA
authors.lastname: Joshi
authors.forename: Pasi A
authors.initials: PA
authors.lastname: Jänne
authors.forename: Daphne W
authors.initials: DW
authors.lastname: Bell
authors.forename: Panos
authors.initials: P
authors.lastname: Fidias
authors.forename: Neal I
authors.initials: NI
authors.lastname: Lindeman
authors.forename: David N
authors.initials: DN
authors.lastname: Louis
authors.forename: Jeffrey C
authors.initials: JC
authors.lastname: Lee
authors.forename: Eugene J
authors.initials: EJ
authors.lastname: Mark
authors.forename: Janina
authors.initials: J
authors.lastname: Longtine
authors.forename: Peter
authors.initials: P
authors.lastname: Verlander
authors.forename: Raju
authors.initials: R
authors.lastname: Kucherlapati
authors.forename: Matthew
authors.initials: M
authors.lastname: Meyerson
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Haber
authors.forename: Bruce E
authors.initials: BE
authors.lastname: Johnson
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Lynch
mesh_terms: D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000628:therapy; D004252:DNA Mutational Analysis / Q000379:methods; D018773:Genes, erbB-1; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000628:therapy; D009154:Mutation