title: Multicenter phase II trial of neoadjuvant therapy with trastuzumab, docetaxel, and carboplatin for human epidermal growth factor receptor-2-overexpressing stage II or III breast cancer: results of the GETN(A)-1 trial.
abstract: OBJECTIVE
  Trastuzumab plus chemotherapy has become the standard of care for human epidermal growth factor receptor-2 (HER-2) -positive breast cancer. Trastuzumab-based preoperative systemic therapy (PST; neoadjuvant therapy) also appears promising, warranting further investigation.
  
  
  METHODS
  Patients with HER-2-positive, stage II/III, noninflammatory, operable breast cancer requiring a mastectomy (but who wanted to conserve the breast) received trastuzumab 4 mg/kg (day 1), followed by 2 mg/kg weekly, plus docetaxel 75 mg/m2 every 3 weeks, and carboplatin (area under curve, 6) for six cycles before surgery. The primary end point was pathologic complete response (pCR) rate, determined from surgical specimens.
  
  
  RESULTS
  Seventy patients were enrolled. Most patients had clinical T2/T3 tumors (100%) or clinical N1/2 nodes (53%). Sixty-seven patients (96%) completed six cycles of therapy, one patient withdrew due to progressive disease, and two patients withdrew for toxicity. A complete or partial objective clinical response occurred in 95% of patients (85% and 10%, respectively). Surgery was breast conservative in 45 (64%) of 70 patients. In an intent-to-treat analysis, tumor and nodal pCR were seen in 27 (39%) of 70 patients. Centralized retrospective analysis of HER-2 status demonstrated a 43% pCR rate in the 24 of 56 confirmed HER-2-overexpressing (3+) and/or fluorescence in situ hybridization-positive tumors. Treatment was generally well tolerated. Grade 3/4 neutropenia and febrile neutropenia were uncommon (2%). Two patients withdrew prematurely due to a transient, asymptomatic decrease in left ventricular ejection fraction. No symptomatic cardiac dysfunction occurred.
  
  
  CONCLUSIONS
  PST with trastuzumab plus docetaxel and carboplatin achieved promising efficacy, with a good pCR rate and favorable tolerability in stage II or III HER-2-positive breast cancer.
authors.affiliation: Department of Oncology, CAC G.F. Leclerc and IFR 100, Dijon, France. bcoudert@dijon.fnclcc.fr
authors.forename: Bruno P
authors.initials: BP
authors.lastname: Coudert
authors.forename: Remy
authors.initials: R
authors.lastname: Largillier
authors.forename: Laurent
authors.initials: L
authors.lastname: Arnould
authors.forename: Philippe
authors.initials: P
authors.lastname: Chollet
authors.forename: Mario
authors.initials: M
authors.lastname: Campone
authors.forename: David
authors.initials: D
authors.lastname: Coeffic
authors.forename: Frank
authors.initials: F
authors.lastname: Priou
authors.forename: Joseph
authors.initials: J
authors.lastname: Gligorov
authors.forename: Xavier
authors.initials: X
authors.lastname: Martin
authors.forename: Véronique
authors.initials: V
authors.lastname: Trillet-Lenoir
authors.forename: Béatrice
authors.initials: B
authors.lastname: Weber
authors.forename: Jean Pierre
authors.initials: JP
authors.lastname: Bleuse
authors.forename: Berangère
authors.initials: B
authors.lastname: Vasseur
authors.forename: Daniel
authors.initials: D
authors.lastname: Serin
authors.forename: Moïse
authors.initials: M
authors.lastname: Namer
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* / Q000378:metabolism* / Q000601:surgery; D016190:Carboplatin / Q000008:administration & dosage*; D017024:Chemotherapy, Adjuvant; D002986:Clinical Trials as Topic; D000077143:Docetaxel; D005260:Female; D006801:Humans; D008207:Lymphatic Metastasis; D008875:Middle Aged; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000096:biosynthesis*; D043823:Taxoids / Q000008:administration & dosage*; D000068878:Trastuzumab; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D016190:Carboplatin; D000077143:Docetaxel; D018719:Erb-b2 Receptor Tyrosine Kinases; D043823:Taxoids; D000068878:Trastuzumab; C508053:ERBB2 protein, human