title: HER-3 status by immunohistochemistry in HER-2-positive metastatic breast cancer patients treated with trastuzumab: correlation with clinical outcome.
abstract: OBJECTIVE
  HER-3 signaling might contribute to resistance to trastuzumab. To clarify the role of HER-3 in HER-2-positive breast cancer, it is important to evaluate the level of HER-3 and its correlations with clinical outcome in metastatic breast cancer patients treated with trastuzumab.
  
  
  METHODS
  HER-3 status by immunohistochemistry was evaluated in HER-2-positive metastatic breast cancer patients treated with trastuzumab-based therapy at our institution. Two scorings were utilized for interpreting staining for HER-3, and the correlation between HER-3 status and clinical outcome was evaluated.
  
  
  RESULTS
  We evaluated HER-3 status in 61 of 76 HER-2-positive metastatic breast cancers treated with trastuzumab-based therapy at our institution from 4/1999 to 3/2006. We observed 55.2% objective responses; median time to progression and overall survival from start of trastuzumab therapy were 9.6 months (0.921-78.87) and 29.1 months (1.4-129.5+), respectively. With a cutoff of 50% staining tumor cells, we found 30 HER-3-negative and 31 HER-3-positive tumors. HER-3 status was not significantly associated with clinical outcome, but a shorter time to progression and overall survival were observed in patients with HER-3-positive tumors.
  
  
  CONCLUSIONS
  HER-3 status by immunohistochemistry was not significantly associated with clinical outcome in HER-2-positive metastatic breast cancer patients. Further studies are necessary to evaluate the prognostic and predictive role of HER-3.
authors.affiliation: Medical Oncology Department, S. Maria della Misericordia Hospital, Azienda Ospedaliera di Perugia, Perugia, Italy. stefania.gori@tin.it
authors.forename: Stefania
authors.initials: S
authors.lastname: Gori
authors.forename: Jennifer
authors.initials: J
authors.lastname: Foglietta
authors.forename: Maria Grazia
authors.initials: MG
authors.lastname: Mameli
authors.forename: Lucia
authors.initials: L
authors.lastname: Stocchi
authors.forename: Daniela
authors.initials: D
authors.lastname: Fenocchio
authors.forename: Paola
authors.initials: P
authors.lastname: Anastasi
authors.forename: Daniela
authors.initials: D
authors.lastname: Iacono
authors.forename: Rachele
authors.initials: R
authors.lastname: Del Sordo
authors.forename: Carlo
authors.initials: C
authors.lastname: Basurto
authors.forename: Verena
authors.initials: V
authors.lastname: De Angelis
authors.forename: Angelo
authors.initials: A
authors.lastname: Sidoni
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000032:analysis*; D001943:Breast Neoplasms / Q000737:chemistry / Q000188:drug therapy* / Q000473:pathology*; D018450:Disease Progression; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis*; D020893:Receptor, ErbB-3 / Q000032:analysis*; D013997:Time Factors; D000068878:Trastuzumab; D016896:Treatment Outcome
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D018719:Erb-b2 Receptor Tyrosine Kinases; D020893:Receptor, ErbB-3; D000068878:Trastuzumab; C508053:ERBB2 protein, human