title: Pilot trial of paclitaxel-trastuzumab adjuvant therapy for early stage breast cancer: a trial of the ECOG-ACRIN cancer research group (E2198).
abstract: BACKGROUND
  Blockade of human epidermal growth factor receptor type 2 (HER2) has dramatically improved outcome for patients with HER2-positive breast cancer. Trastuzumab, an anti-HER2 monoclonal antibody, has previously demonstrated improvement in overall survival (OS) in patients with metastatic and early stage HER2-positive breast cancer. However, trastuzumab can cause congestive heart failure (CHF) with an increased frequency for patients who have also received an anthracycline. The current trial was designed to evaluate the impact of the duration of trastuzumab on CHF.
  
  
  METHODS
  E2198 included 227 eligible women with histologically confirmed stage II or IIIA HER2-positive breast cancer. The patients were randomised to receive 12 weeks of paclitaxel and trastuzumab followed by four cycles of doxorubicin and cyclophosphamide (abbreviated Arm) or the aforementioned treatment with additional 1 year of trastuzumab (conventional Arm). The primary end point was to evaluate the safety of this variable duration of trastuzumab therapy, particularly cardiac toxicity defined as CHF or left ventricular ejection fraction decrease >10%. Secondary end points included disease-free survival (DFS) and OS.
  
  
  RESULTS
  Compared with 12-week treatment with trastuzumab, 1 year of trastuzumab-based therapy did not increase the frequency or severity of cardiac toxicity: three patients on the abbreviated Arm and four on the conventional Arm experienced CHF. The 5-year DFS was 76% and 73% for the abbreviated and conventional Arms, respectively, with a hazard ratio (HR) of 1.3 (95% CI: 0.8-2.1; P=0.3). There was also no statistically significance difference in OS (HR, 1.4; P=0.3).
  
  
  CONCLUSIONS
  Compared with 12 weeks of treatment, 1 year of treatment with trastuzumab did not significantly increase the risk of cardiac toxicity. Although not powered for efficacy comparisons, the longer duration of trastuzumab therapy did not demonstrate a signal for marked superiority.
authors.affiliation: Department of Medicine, Indiana University Medical Center, Indianapolis, IN 46033, USA.
authors.forename: Bryan P
authors.initials: BP
authors.lastname: Schneider
authors.affiliation: Department of Biostatistics and Computational Biology, Dana Farber Cancer Institute, Boston, MA 02215, USA.
authors.forename: Anne
authors.initials: A
authors.lastname: O'Neill
authors.affiliation: Department of Medicine, Indiana University Medical Center, Indianapolis, IN 46033, USA.
authors.forename: Fei
authors.initials: F
authors.lastname: Shen
authors.affiliation: Department of Medicine, Stanford Medical Center, Stanford University, Stanford, CA 94305, USA.
authors.forename: George W
authors.initials: GW
authors.lastname: Sledge
authors.affiliation: Department of Pathology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73126, USA.
authors.forename: Ann D
authors.initials: AD
authors.lastname: Thor
authors.affiliation: Hematology-Oncology Associates, Sioux City Mercy Medical Center, Sioux City, IA 51101, USA.
authors.forename: Stephen P
authors.initials: SP
authors.lastname: Kahanic
authors.affiliation: Department of Hematology and Oncology, Abbott Northwestern Hospital, Minneapolis, MN 55407, USA.
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Zander
authors.affiliation: Department of Medicine, University of Pittsburgh Cancer Institute and UMPC Cancer Center, Pittsburgh, PA 15232, USA.
authors.forename: Nancy E
authors.initials: NE
authors.lastname: Davidson
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy*; D017024:Chemotherapy, Adjuvant; D005260:Female; D006801:Humans; D008875:Middle Aged; D017239:Paclitaxel / Q000008:administration & dosage; D010865:Pilot Projects; D000068878:Trastuzumab / Q000008:administration & dosage
chemical_list: D000068878:Trastuzumab; D017239:Paclitaxel