title: HER2 overexpression and doxorubicin in adjuvant chemotherapy for resectable breast cancer.
abstract: OBJECTIVE
  Human epidermal growth factor receptor 2 (HER2) overexpression was found to predict a good response in breast carcinoma patients treated with doxorubicin (Adriamycin [ADM]). Evidence from our recent study indicates that node-positive patients respond to cyclophosphamide, methotrexate, and fluorouracil (CMF) regardless of HER2 status. We address the issue of whether therapy regimens including CMF and ADM versus CMF alone have the same therapeutic effect in patients with HER2+ and HER2- tumors in terms of relapse-free survival (RFS) and overall survival (OS).
  
  
  METHODS
  Archival specimens of the primary tumors from 506 patients in a prospective clinical trial were stained with the anti-HER2 monoclonal antibody CB11. Originally, patients were randomly allocated to receive either 12 courses of intravenous CMF or eight courses of the same regimen followed by four cycles of ADM. RFS and OS were analyzed by a Cox model taking into account treatment, HER2 status, and the interaction between treatment and HER2 status, adjusting for the effect of other known clinical and biopathologic factors.
  
  
  RESULTS
  Analysis of survival rates indicates a possible differential effect of treatment in the patients grouped according to HER2 status. Improved RFS and OS were observed in the HER2+ subgroup after treatment with CMF plus ADM versus CMF alone. With a median follow-up of 15 years, the hazard ratio (HR) for RFS was 0.83 in HER2+ tumors and 1.22 in HER2- tumors. The effect of treatment was more evident on OS in HER2+ patients (HR = 0.61; CI, 0.32 to 1.16) than in HER2- patients (HR = 1.26).
  
  
  CONCLUSIONS
  Our data indicate that adding ADM to CMF might be beneficial for patients with HER2+ tumors.
authors.affiliation: Medical Oncology Unit, Department of Experimental Oncology, Scientific Direction, Istituto Nazionale Tumori, Italy.
authors.forename: Angela
authors.initials: A
authors.lastname: Moliterni
authors.forename: Sylvie
authors.initials: S
authors.lastname: Ménard
authors.forename: Pinuccia
authors.initials: P
authors.lastname: Valagussa
authors.forename: Elia
authors.initials: E
authors.lastname: Biganzoli
authors.forename: Patrizia
authors.initials: P
authors.lastname: Boracchi
authors.forename: Andrea
authors.initials: A
authors.lastname: Balsari
authors.forename: Patrizia
authors.initials: P
authors.lastname: Casalini
authors.forename: Gorana
authors.initials: G
authors.lastname: Tomasic
authors.forename: Ettore
authors.initials: E
authors.lastname: Marubini
authors.forename: Silvana
authors.initials: S
authors.lastname: Pilotti
authors.forename: Gianni
authors.initials: G
authors.lastname: Bonadonna
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D017024:Chemotherapy, Adjuvant; D003520:Cyclophosphamide / Q000008:administration & dosage; D004317:Doxorubicin / Q000627:therapeutic use*; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008727:Methotrexate / Q000008:administration & dosage; D008875:Middle Aged; D011237:Predictive Value of Tests; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis / Q000096:biosynthesis*; D013534:Survival
chemical_list: D000970:Antineoplastic Agents; D003520:Cyclophosphamide; D004317:Doxorubicin; D005472:Fluorouracil; D008727:Methotrexate; D018719:Erb-b2 Receptor Tyrosine Kinases