title: Docetaxel combined with trastuzumab is an active regimen in HER-2 3+ overexpressing and fluorescent in situ hybridization-positive metastatic breast cancer: a multi-institutional phase II trial.
abstract: OBJECTIVE
  To determine the efficacy and safety of weekly docetaxel and trastuzumab as first- or second-line therapy in women with HER-2-overexpressing metastatic breast cancer and to correlate the efficacy of trastuzumab with HER-2 status as determined by immunohistochemistry assay and fluorescent in situ hybridization (FISH).
  
  
  METHODS
  Twenty-six women with HER-2-positive (HercepTest [Dako Corp, Carpenteria, CA]2 to 3+) metastatic breast cancer were enrolled onto this study of trastuzumab (4 mg/kg load; 2 mg/kg/wk administered intravenously) and docetaxel (35 mg/m2/wk for 6 weeks).
  
  
  RESULTS
  Using an intent-to-treat analysis, the overall response rate was 50% (13 of 26 patients). Eight patients (31%) had a period of stable disease posttherapy. Among HER-2 3+ patients, the overall response rate was 63% (12 of 19 patients) compared with a 14% response rate (one of seven patients) for HER-2 2+ patients (P=.07). Patients with FISH-positive tumors experienced an overall response rate of 64%. Median time to progression was 12.4 months for the entire cohort (HER-2 3+ tumors, 12.3 months; HER-2 2+ lesions, 9.5 months) and median survival was 22.1 months. All HER-2 3+ patients were FISH-positive; the only HER-2 2+ patient responding to treatment was also FISH-positive. Grade 4 toxicities occurred in four patients; most toxicities were mild.
  
  
  CONCLUSIONS
  Trastuzumab plus docetaxel is an active and well-tolerated regimen in women with HER-2 3+ overexpressing or FISH-positive metastatic breast cancer.
authors.affiliation: Vanderbilt Clinic, Vanderbilt University Medical Center, Nashville, TN, USA.
authors.forename: K L
authors.initials: KL
authors.lastname: Tedesco
authors.forename: A D
authors.initials: AD
authors.lastname: Thor
authors.forename: D H
authors.initials: DH
authors.lastname: Johnson
authors.forename: Y
authors.initials: Y
authors.lastname: Shyr
authors.forename: K A
authors.initials: KA
authors.lastname: Blum
authors.forename: L J
authors.initials: LJ
authors.lastname: Goldstein
authors.forename: W J
authors.initials: WJ
authors.lastname: Gradishar
authors.forename: B P
authors.initials: BP
authors.lastname: Nicholson
authors.forename: D E
authors.initials: DE
authors.lastname: Merkel
authors.forename: D
authors.initials: D
authors.lastname: Murrey
authors.forename: S
authors.initials: S
authors.lastname: Edgerton
authors.forename: G W
authors.initials: GW
authors.lastname: Sledge
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D018572:Disease-Free Survival; D000077143:Docetaxel; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008875:Middle Aged; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D020893:Receptor, ErbB-3 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D016019:Survival Analysis; D043823:Taxoids / Q000008:administration & dosage; D000068878:Trastuzumab; D014481:United States; D015854:Up-Regulation
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000077143:Docetaxel; D018719:Erb-b2 Receptor Tyrosine Kinases; D020893:Receptor, ErbB-3; D043823:Taxoids; D000068878:Trastuzumab