title: Level of HER2/neu amplification in primary tumours and metastases in HER2-positive breast cancer and survival after trastuzumab therapy.
abstract: BACKGROUND
  The level of HER2/neu amplification may vary widely in breast cancers with HER2/neu alteration. The clinical significance of this phenomenon is still unclear. This study was aimed to explore the level of HER2/neu amplification in primary tumours and metastases in HER2-positive metastatic breast cancer (MBC) and its potential impact on survival after a trastuzumab-containing therapy.
  
  
  METHODS
  We retrospectively identified MBC patients treated with a trastuzumab-containing therapy and performed dual-colour FISH on tumour samples from either primary tumour and/or metastasis in a central laboratory.
  
  
  RESULTS
  We retrieved 110 tumour samples from 91 patients and included 79 tumour samples (primary = 56; metastasis = 23) from 63 patients in the final analysis. We found higher level of HER2/neu amplification in the metastases than in the primary tumours (median HER2/CEP17 ratio: 10.5 vs. 7.0, respectively). In 69% of patients (n = 16) with two tumour samples, the level of HER2/neu amplification was higher in the metastasis than in the paired primary tumour (median HER2/CEP17 ratio: 10.9 vs. 8.3, respectively, p = 0.004). The incremental gain in level of HER2/neu amplification was associated with significantly shorter OS after trastuzumab-containing therapy (p = 0.023, HR 1.014, CI95%: 1.002-1.025).
  
  
  CONCLUSIONS
  The level of HER2/neu amplification tends to increase from the primary tumour to the paired metastases in a significant proportion of patients with HER2-positive MBC. This phenomenon, although still not completely understood, could lead to a shorter OS after trastuzumab therapy.
authors.affiliation: Oncology Department, St Vincent's University Hospital, Merrion Road, Dublin, Ireland. Electronic address: g.gullo@svuh.ie.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Gullo
authors.affiliation: Laboratory of Cytogenetics, Humanitas Clinical and Research Center, Via Manzoni 56, 20089 Rozzano (Mi), Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Bettio
authors.affiliation: Oncology and Haematology Unit, Humanitas Clinical and Research Center, Italy.
authors.forename: Monica
authors.initials: M
authors.lastname: Zuradelli
authors.affiliation: Oncology and Haematology Unit, Humanitas Clinical and Research Center, Italy.
authors.forename: Giovanna
authors.initials: G
authors.lastname: Masci
authors.affiliation: Biostatistic Unit, Humanitas Clinical and Research Center, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Giordano
authors.affiliation: Medical Oncology Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milano, Italy.
authors.forename: Claudia
authors.initials: C
authors.lastname: Bareggi
authors.affiliation: Medical Oncology Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milano, Italy.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Tomirotti
authors.affiliation: Medical Oncology Unit, Cliniche Humanitas Gavazzeni, Bergamo, Italy.
authors.forename: Piermario
authors.initials: P
authors.lastname: Salvini
authors.affiliation: Pathology Department, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milano, Italy.
authors.forename: Letterio
authors.initials: L
authors.lastname: Runza
authors.affiliation: Department of Oncology, A.O. Fatebenefratelli e Oftalmico, Milano, Italy.
authors.forename: Nicla
authors.initials: N
authors.lastname: La Verde
authors.affiliation: Oncology and Haematology Unit, Humanitas Clinical and Research Center, Italy.
authors.forename: Armando
authors.initials: A
authors.lastname: Santoro
mesh_terms: D000328:Adult; D000368:Aged; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism* / Q000401:mortality / Q000556:secondary; D018270:Carcinoma, Ductal, Breast / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism* / Q000401:mortality / Q000556:secondary; D005260:Female; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008875:Middle Aged; D009376:Neoplasms, Hormone-Dependent / Q000378:metabolism*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D000068878:Trastuzumab
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab; C508053:ERBB2 protein, human