title: EGFR Testing in Advanced Non-Small-Cell Lung Cancer, A Mini-Review.
abstract: Expert consensus guidelines have defined minimum requirements for routine testing and identification of classical epidermal growth factor (EGFR) mutations (ie, exon 19 deletions and exon 21 L858R substitution) and anaplastic lymphoma kinase (ALK) rearrangements in advanced non-small-cell lung cancers of adenocarcinoma histology, with the intent of permitting use of these predictive biomarkers to select patients who will derive maximal benefit from approved oral tyrosine kinase inhibitors (TKIs) directed against EGFR and ALK, respectively. However, the practice of precision medicine is incumbent upon optimal tumor sampling, accurate tumor testing, and informed application of results to patient care. We report on a brief review of EGFR testing methodologies (Sanger sequencing, allele-specific polymerase chain reaction, and targeted next-generation sequencing) to identify classical and other (ie, exon 18 G719X, exon 19 insertions, exon 20 insertions, exon 21 L861Q) EGFR mutations; practical considerations (type of tissue/biopsies with different success rates of DNA isolation, and timeliness of result-reporting to facilitate therapeutic decision-making); role of rebiopsy (to identify mechanisms of acquired resistance to first- and second-generation EGFR TKIs, most importantly EGFR-T790M); and clinical vignettes highlighting the nuances of testing in day-to-day practice.
authors.affiliation: Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA.
authors.forename: Yuri
authors.initials: Y
authors.lastname: Sheikine
authors.affiliation: Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA.
authors.forename: Deepa
authors.initials: D
authors.lastname: Rangachari
authors.affiliation: Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA.
authors.forename: Danielle C
authors.initials: DC
authors.lastname: McDonald
authors.affiliation: Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA.
authors.forename: Mark S
authors.initials: MS
authors.lastname: Huberman
authors.affiliation: Department of Surgery, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA.
authors.forename: Erik S
authors.initials: ES
authors.lastname: Folch
authors.affiliation: Department of Pathology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA.
authors.forename: Paul A
authors.initials: PA
authors.lastname: VanderLaan
authors.affiliation: Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA. Electronic address: dbcosta@bidmc.harvard.edu.
authors.forename: Daniel B
authors.initials: DB
authors.lastname: Costa
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics; D066246:ErbB Receptors / Q000235:genetics*; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics; D058990:Molecular Targeted Therapy; D009154:Mutation / Q000235:genetics*; D057285:Precision Medicine; D011237:Predictive Value of Tests
chemical_list: D000970:Antineoplastic Agents; C512478:EGFR protein, human; D066246:ErbB Receptors
keywords: Adenocarcinoma; Afatinib; Erlotinib; Exon 19; Gefitinib; L858R; Osimertinib; T790M; TKI