title: Weekly trastuzumab and paclitaxel therapy for metastatic breast cancer with analysis of efficacy by HER2 immunophenotype and gene amplification.
abstract: OBJECTIVE
  This phase II study evaluated weekly trastuzumab and paclitaxel therapy in women with HER2-normal and HER2-overexpressing metastatic breast cancer. Efficacy was correlated with immunohistochemical and fluorescent in situ hybridization (FISH) assay results.
  
  
  METHODS
  Eligible patients had bidimensionally measurable metastatic breast cancer. Up to three prior chemotherapy regimens, including prior anthracycline and taxane therapy, were allowed. Trastuzumab 4 mg/kg and paclitaxel 90 mg/m2 were administered on week 1, with trastuzumab 2 mg/kg and paclitaxel 90 mg/m2 administered on subsequent weeks. HER2 status was evaluated using four different immunohistochemical assays and FISH.
  
  
  RESULTS
  Patients received a median of 25 weekly infusions (range, one to 85 infusions). Median delivered paclitaxel dose-intensity was 82 mg/m2/wk (range, 52 to 90 mg/m2/wk). The intent-to-treat response rate for all 95 patients enrolled was 56.8% (95% confidence interval, 47% to 67%). A response rate of 61.4% (4.5% complete response, 56.8% partial response) was observed in 88 fully assessable patients. In patients with HER2-overexpressing tumors, overall response rates ranged from 67% to 81% compared with 41% to 46% in patients with HER2-normal expression (ranges reflect the different assay methods used to assess HER2 status). Differences in response rates between patients with HER2-overexpressing tumors and those with normal HER2 expression were statistically significant for all assay methods, with CB11 and TAB250 antibodies and FISH having the strongest significance. Therapy was generally well tolerated, although three patients had serious cardiac complications.
  
  
  CONCLUSIONS
  Weekly trastuzumab and paclitaxel therapy is active in women with metastatic breast cancer. Therapy was relatively well tolerated; however, attention to cardiac function is necessary.
authors.affiliation: Breast Cancer Medicine Service, Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA. seidmana@mskcc.org
authors.forename: A D
authors.initials: AD
authors.lastname: Seidman
authors.forename: M N
authors.initials: MN
authors.lastname: Fornier
authors.forename: F J
authors.initials: FJ
authors.lastname: Esteva
authors.forename: L
authors.initials: L
authors.lastname: Tan
authors.forename: S
authors.initials: S
authors.lastname: Kaptain
authors.forename: A
authors.initials: A
authors.lastname: Bach
authors.forename: K S
authors.initials: KS
authors.lastname: Panageas
authors.forename: C
authors.initials: C
authors.lastname: Arroyo
authors.forename: V
authors.initials: V
authors.lastname: Valero
authors.forename: V
authors.initials: V
authors.lastname: Currie
authors.forename: T
authors.initials: T
authors.lastname: Gilewski
authors.forename: M
authors.initials: M
authors.lastname: Theodoulou
authors.forename: M E
authors.initials: ME
authors.lastname: Moynahan
authors.forename: M
authors.initials: M
authors.lastname: Moasser
authors.forename: N
authors.initials: N
authors.lastname: Sklarin
authors.forename: M
authors.initials: M
authors.lastname: Dickler
authors.forename: G
authors.initials: G
authors.lastname: D'Andrea
authors.forename: M
authors.initials: M
authors.lastname: Cristofanilli
authors.forename: E
authors.initials: E
authors.lastname: Rivera
authors.forename: G N
authors.initials: GN
authors.lastname: Hortobagyi
authors.forename: L
authors.initials: L
authors.lastname: Norton
authors.forename: C A
authors.initials: CA
authors.lastname: Hudis
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000556:secondary; D004334:Drug Administration Schedule; D005260:Female; D005784:Gene Amplification; D018734:Genes, erbB-2 / Q000276:immunology*; D006801:Humans; D016130:Immunophenotyping; D017404:In Situ Hybridization, Fluorescence; D008875:Middle Aged; D017239:Paclitaxel / Q000008:administration & dosage; D000068878:Trastuzumab; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000068878:Trastuzumab; D017239:Paclitaxel