title: Adjuvant trastuzumab in HER2-positive breast cancer.
abstract: BACKGROUND
  Trastuzumab improves survival in the adjuvant treatment of HER-positive breast cancer, although combined therapy with anthracycline-based regimens has been associated with cardiac toxicity. We wanted to evaluate the efficacy and safety of a new nonanthracycline regimen with trastuzumab.
  
  
  METHODS
  We randomly assigned 3222 women with HER2-positive early-stage breast cancer to receive doxorubicin and cyclophosphamide followed by docetaxel every 3 weeks (AC-T), the same regimen plus 52 weeks of trastuzumab (AC-T plus trastuzumab), or docetaxel and carboplatin plus 52 weeks of trastuzumab (TCH). The primary study end point was disease-free survival. Secondary end points were overall survival and safety.
  
  
  RESULTS
  At a median follow-up of 65 months, 656 events triggered this protocol-specified analysis. The estimated disease-free survival rates at 5 years were 75% among patients receiving AC-T, 84% among those receiving AC-T plus trastuzumab, and 81% among those receiving TCH. Estimated rates of overall survival were 87%, 92%, and 91%, respectively. No significant differences in efficacy (disease-free or overall survival) were found between the two trastuzumab regimens, whereas both were superior to AC-T. The rates of congestive heart failure and cardiac dysfunction were significantly higher in the group receiving AC-T plus trastuzumab than in the TCH group (P<0.001). Eight cases of acute leukemia were reported: seven in the groups receiving the anthracycline-based regimens and one in the TCH group subsequent to receiving an anthracycline outside the study.
  
  
  CONCLUSIONS
  The addition of 1 year of adjuvant trastuzumab significantly improved disease-free and overall survival among women with HER2-positive breast cancer. The risk-benefit ratio favored the nonanthracycline TCH regimen over AC-T plus trastuzumab, given its similar efficacy, fewer acute toxic effects, and lower risks of cardiotoxicity and leukemia. (Funded by Sanofi-Aventis and Genentech; BCIRG-006 ClinicalTrials.gov number, NCT00021255.).
authors: Jonsson Comprehensive Cancer Center, University of California–Los Angeles, Los Angeles, CA 90095-1678, USA. dslamon@mednet.ucla.edu
authors: Dennis
authors: D
authors: Slamon
authors: Wolfgang
authors: W
authors: Eiermann
authors: Nicholas
authors: N
authors: Robert
authors: Tadeusz
authors: T
authors: Pienkowski
authors: Miguel
authors: M
authors: Martin
authors: Michael
authors: M
authors: Press
authors: John
authors: J
authors: Mackey
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authors: J
authors: Glaspy
authors: Arlene
authors: A
authors: Chan
authors: Marek
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authors: Pawlicki
authors: Tamas
authors: T
authors: Pinter
authors: Vicente
authors: V
authors: Valero
authors: Mei-Ching
authors: MC
authors: Liu
authors: Guido
authors: G
authors: Sauter
authors: Gunter
authors: G
authors: von Minckwitz
authors: Frances
authors: F
authors: Visco
authors: Valerie
authors: V
authors: Bee
authors: Marc
authors: M
authors: Buyse
authors: Belguendouz
authors: B
authors: Bendahmane
authors: Isabelle
authors: I
authors: Tabah-Fisch
authors: Mary-Ann
authors: MA
authors: Lindsay
authors: Alessandro
authors: A
authors: Riva
authors: John
authors: J
authors: Crown
mesh_terms: D018943:Anthracyclines / Q000009:adverse effects / Q000627:therapeutic use; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000401:mortality; D017024:Chemotherapy, Adjuvant; D018572:Disease-Free Survival; D005260:Female; D006333:Heart Failure / Q000139:chemically induced; D006801:Humans; D057194:Intention to Treat Analysis; D007938:Leukemia / Q000139:chemically induced; D008875:Middle Aged; D018719:Erb-b2 Receptor Tyrosine Kinases; D013318:Stroke Volume / Q000187:drug effects; D015996:Survival Rate; D000068878:Trastuzumab
chemical_list: D018943:Anthracyclines; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab