title: Molecular effects of lapatinib in patients with HER2 positive ductal carcinoma in situ.
abstract: BACKGROUND
  Human epidermal growth factor receptor 2 (HER2) amplification is frequent in ductal carcinoma in situ (DCIS) of the breast and is associated with poorly differentiated tumors and adverse prognosis features. This study aimed to determine the molecular effects of the HER2 inhibitor lapatinib in patients with HER2 positive DCIS.
  
  
  METHODS
  Patients with HER2 positive DCIS received 1,500 mg daily of lapatinib for four consecutive weeks prior to surgical resection. Magnetic resonance imaging (MRI) was used to determine changes in tumor volume. The molecular effects of lapatinib on HER2 signaling (PI3K/AKT and RAS/MAPK pathways), cell proliferation (Ki67 and p27) and apoptosis (TUNEL) were determined in pre and post-lapatinib treatment samples.
  
  
  RESULTS
  A total of 20 patients were included. Lapatinib was well tolerated with only minor and transient side effects. The agent effectively modulated HER2 signaling decreasing significantly pHER2 and pERK1 expression, together with a decrease in tumor size evaluated by MRI. There was no evidence of changes in Ki67.
  
  
  CONCLUSIONS
  Four weeks of neoadjuvant lapatinib in patients with HER2-positive DCIS resulted in inhibition of HER2 and RAS/MAPK signaling pathway.
  
  
  BACKGROUND
  2008-004492-21 (Registered June 25th 2008).
authors.affiliation: Breast Cancer Program, Centro Integral Oncológico Clara Campal, C/Oña 10, Madrid, 28050, Spain. lestevez@hmhospitales.com.
authors.forename: Laura G
authors.initials: LG
authors.lastname: Estévez
authors.affiliation: Breast Cancer Program, Centro Integral Oncológico Clara Campal, C/Oña 10, Madrid, 28050, Spain. asuarez@hmhospitales.com.
authors.forename: Ana
authors.initials: A
authors.lastname: Suarez-Gauthier
authors.affiliation: Pathology Department, Hospital Universitario Fundación Alcorcón, Madrid, 28922, Spain. egarcia@fhalcorcon.es.
authors.forename: Elena
authors.initials: E
authors.lastname: García
authors.affiliation: Breast Cancer Program, Centro Integral Oncológico Clara Campal, C/Oña 10, Madrid, 28050, Spain. cmiro@hmhospitales.com.
authors.forename: Cristina
authors.initials: C
authors.lastname: Miró
authors.affiliation: Breast Cancer Program, Centro Integral Oncológico Clara Campal, C/Oña 10, Madrid, 28050, Spain. icalvo@hmhospitales.com.
authors.forename: Isabel
authors.initials: I
authors.lastname: Calvo
authors.affiliation: Breast Cancer Program, Centro Integral Oncológico Clara Campal, C/Oña 10, Madrid, 28050, Spain. mfabad@hmhospitales.com.
authors.forename: María
authors.initials: M
authors.lastname: Fernández-Abad
authors.affiliation: Breast Cancer Program, Centro Integral Oncológico Clara Campal, C/Oña 10, Madrid, 28050, Spain. mherrero@hmhospitales.com.
authors.forename: Mercedes
authors.initials: M
authors.lastname: Herrero
authors.affiliation: Breast Cancer Program, Centro Integral Oncológico Clara Campal, C/Oña 10, Madrid, 28050, Spain. mmarcos@hmhospitales.com.
authors.forename: Manuel
authors.initials: M
authors.lastname: Marcos
authors.affiliation: Breast Cancer Program, Centro Integral Oncológico Clara Campal, C/Oña 10, Madrid, 28050, Spain. cmarquez@hmhospitales.com.
authors.forename: Cristina
authors.initials: C
authors.lastname: Márquez
authors.affiliation: Breast Cancer Program, Centro Integral Oncológico Clara Campal, C/Oña 10, Madrid, 28050, Spain. flopezrios@hmhospitales.com.
authors.forename: Fernando
authors.initials: F
authors.lastname: Lopez Ríos
authors.affiliation: Breast Cancer Program, Centro Integral Oncológico Clara Campal, C/Oña 10, Madrid, 28050, Spain. sperea@hmhospitales.com.
authors.forename: Sofía
authors.initials: S
authors.lastname: Perea
authors.affiliation: Breast Cancer Program, Centro Integral Oncológico Clara Campal, C/Oña 10, Madrid, 28050, Spain. mhidalgo@cnio.es.|Clinical Research Program, Spanish National Cancer Research Center, Madrid, 28029, Spain. mhidalgo@cnio.es.
authors.forename: Manuel
authors.initials: M
authors.lastname: Hidalgo
mesh_terms: D000328:Adult; D000368:Aged; D017209:Apoptosis / Q000187:drug effects; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D002285:Carcinoma, Intraductal, Noninfiltrating / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D049109:Cell Proliferation / Q000187:drug effects; D066246:ErbB Receptors / Q000096:biosynthesis / Q000235:genetics; D005260:Female; D005784:Gene Amplification / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D000077341:Lapatinib; D008875:Middle Aged; D020929:Mitogen-Activated Protein Kinase Kinases / Q000187:drug effects / Q000235:genetics; D011379:Prognosis; D011799:Quinazolines / Q000008:administration & dosage* / Q000009:adverse effects; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000096:biosynthesis / Q000235:genetics*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D066246:ErbB Receptors; D000077341:Lapatinib; D020929:Mitogen-Activated Protein Kinase Kinases; D011799:Quinazolines; D018719:Erb-b2 Receptor Tyrosine Kinases; C512478:EGFR protein, human; C508053:ERBB2 protein, human