title: HER2 overexpression as a predictive marker in a randomized trial comparing adjuvant cyclophosphamide/methotrexate/5-fluorouracil with epirubicin in patients with stage I/II breast cancer: long-term results.
abstract: BACKGROUND
  HER2 overexpression/amplification has been reported to be a predictor of prognosis in breast cancer and a potential marker for selecting the optimal adjuvant chemotherapy.
  
  
  METHODS
  HER2 expression and its interaction with treatment were retrospectively evaluated in 266 of 348 patients in a trial comparing adjuvant CMF (cyclophosphamide/methotrexate/5-fluorouracil) with weekly epirubicin in stage I/II breast cancer. HER2 expression was determined by immunohistochemistry (IHC) using the monoclonal antibody CB11. Initially, any cell showing definite membrane staining was counted, and HER2 overexpression was analyzed as a continuous variable and as a dichotomous variable, with a cutoff of > 50% of positively stained cells. Subsequently, the same slides were reanalyzed with the HercepTest.
  
  
  RESULTS
  Of the 266 tumors immunostained for HER2, 34% exhibited nearly homogeneous staining with > 50% positive cells. When the HercepTest was applied, 8% of tumors were IHC 3+ and 8% were IHC 2+. At 8 years, no statistically significant difference in relapse-free survival (RFS) and overall survival (OS) was observed between the treatment arms in patients with low versus high HER2 overexpression, although the number of events is low. The OS was statistically shorter in patients with high HER2 overexpression in the CMF arm, whereas no difference was observed in the epirubicin arm, suggesting that patients whose cancer overexpresses HER2 could benefit more from anthracycline-based therapy.
  
  
  CONCLUSIONS
  HER2 overexpression was associated with a poorer OS but not a poorer RFS. However, a Cox regression model did not confirm the prognostic role of HER2 for OS.
authors.affiliation: Medical Oncology Division, Azienda Ospedaliera, Sant'Andrea delle Fratte, Perugia, Italy. mariantonietta.colozza@tin.it
authors.forename: Mariantonietta
authors.initials: M
authors.lastname: Colozza
authors.forename: Angelo
authors.initials: A
authors.lastname: Sidoni
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Mosconi
authors.forename: Antonio
authors.initials: A
authors.lastname: Cavaliere
authors.forename: Giancarlo
authors.initials: G
authors.lastname: Bisagni
authors.forename: Stefania
authors.initials: S
authors.lastname: Gori
authors.forename: Verena
authors.initials: V
authors.lastname: De Angelis
authors.forename: Antonio
authors.initials: A
authors.lastname: Frassoldati
authors.forename: Roberta
authors.initials: R
authors.lastname: Cherubini
authors.forename: Alberto Rosa
authors.initials: AR
authors.lastname: Bian
authors.forename: Carmelina
authors.initials: C
authors.lastname: Rodino
authors.forename: Bruno
authors.initials: B
authors.lastname: Mazzocchi
authors.forename: Zhasmina
authors.initials: Z
authors.lastname: Mihailova
authors.forename: Emilio
authors.initials: E
authors.lastname: Bucciarelli
authors.forename: Maurizio
authors.initials: M
authors.lastname: Tonato
mesh_terms: D000328:Adult; D000903:Antibiotics, Antineoplastic / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000096:biosynthesis / Q000235:genetics*; D001943:Breast Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D017024:Chemotherapy, Adjuvant; D003520:Cyclophosphamide / Q000008:administration & dosage; D015251:Epirubicin / Q000627:therapeutic use*; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D018734:Genes, erbB-2 / Q000235:genetics*; D006801:Humans; D008408:Mastectomy; D008727:Methotrexate / Q000008:administration & dosage; D008875:Middle Aged; D009367:Neoplasm Staging; D011237:Predictive Value of Tests; D011379:Prognosis; D016032:Randomized Controlled Trials as Topic; D012189:Retrospective Studies; D016019:Survival Analysis
chemical_list: D000903:Antibiotics, Antineoplastic; D014408:Biomarkers, Tumor; D015251:Epirubicin; D003520:Cyclophosphamide; D005472:Fluorouracil; D008727:Methotrexate