title: Epidermal growth factor receptor gene copy number may predict lapatinib sensitivity in HER2-positive metastatic breast cancer.
abstract: OBJECTIVE
  Lapatinib, a dual HER2/EGFR tyrosine kinase inhibitor (TKI), associated to capecitabine represents the treatment of choice in HER2-positive metastatic breast cancer (BC) patients in progression after trastuzumab-based therapy. Though lapatinib-based therapy prolongs the time to progression, its efficacy is often limited by the development of drug resistance. It is aimed to evaluate novel biomarkers predictive of lapatinib response, we analyzed EGFR protein and gene status in a series of 50 metastatic HER2-positive BC patients.
  
  
  METHODS
  Lapatinib was given at 1250 mg/day continuously and capecitabine at 2000 mg/m(2)/day every 3 weeks. EGFR protein expression and gene copy number (GCN) were assessed by immunohistochemistry and FISH, respectively. Receiver operating curve (ROC) analysis identified the value of > 3.36 EGFR copies/nucleus as the cut-off point able to discriminate responders versus non-responders.
  
  
  RESULTS
  A statistical significant correlation between EGFR GCN value > 3.36 and response to lapatinib (p = 0.01) was found. Cox regression analysis further supported these findings evidencing that HER2 score 3+ and EGFR GCN increase are positive predictor factors of lapatinib response.
  
  
  CONCLUSIONS
  Though further investigations are needed to confirm these findings, EGFR GCN could be a suitable screening to identify the subset of BC patients particularly responsive to the dual TKI lapatinib.
authors.affiliation: Regina Elena National Cancer Institute, Department of Oncology A, Via Elio Chianesi, 53, 00144 Rome, Italy. fabi@ifo.it
authors.forename: Alessandra
authors.initials: A
authors.lastname: Fabi
authors.forename: Roberta
authors.initials: R
authors.lastname: Merola
authors.forename: Gianluigi
authors.initials: G
authors.lastname: Ferretti
authors.forename: Anna
authors.initials: A
authors.lastname: Di Benedetto
authors.forename: Barbara
authors.initials: B
authors.lastname: Antoniani
authors.forename: Cristiana
authors.initials: C
authors.lastname: Ercolani
authors.forename: Cecilia
authors.initials: C
authors.lastname: Nisticò
authors.forename: Paola
authors.initials: P
authors.lastname: Papaldo
authors.forename: Mariangela
authors.initials: M
authors.lastname: Ciccarese
authors.forename: Isabella
authors.initials: I
authors.lastname: Sperduti
authors.forename: Patrizia
authors.initials: P
authors.lastname: Vici
authors.forename: Mirella
authors.initials: M
authors.lastname: Marino
authors.forename: Stefania
authors.initials: S
authors.lastname: Gori
authors.forename: Claudio
authors.initials: C
authors.lastname: Botti
authors.forename: Paola
authors.initials: P
authors.lastname: Malaguti
authors.forename: Francesco
authors.initials: F
authors.lastname: Cognetti
authors.forename: Marcella
authors.initials: M
authors.lastname: Mottolese
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000494:pharmacology*; D015415:Biomarkers / Q000378:metabolism; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D019008:Drug Resistance, Neoplasm; D066246:ErbB Receptors / Q000235:genetics*; D005260:Female; D018628:Gene Dosage; D006801:Humans; D000077341:Lapatinib; D008875:Middle Aged; D009362:Neoplasm Metastasis; D016016:Proportional Hazards Models; D011446:Prospective Studies; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011799:Quinazolines / Q000494:pharmacology*; D012372:ROC Curve; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D012044:Regression Analysis
chemical_list: D000970:Antineoplastic Agents; D015415:Biomarkers; D066246:ErbB Receptors; D000077341:Lapatinib; D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D018719:Erb-b2 Receptor Tyrosine Kinases