title: Trastuzumab plus adjuvant chemotherapy for human epidermal growth factor receptor 2-positive breast cancer: planned joint analysis of overall survival from NSABP B-31 and NCCTG N9831.
abstract: OBJECTIVE
  Positive interim analysis findings from four large adjuvant trials evaluating trastuzumab in patients with early-stage human epidermal growth factor receptor 2 (HER2) -positive breast cancer were first reported in 2005. One of these reports, the joint analysis of North Central Cancer Treatment Group NCCTG N9831 (Combination Chemotherapy With or Without Trastuzumab in Treating Women With HER2-Overexpressing Breast Cancer) and the National Surgical Adjuvant Breast and Bowel Project NSABP B-31 (Doxorubicin and Cyclophosphamide Plus Paclitaxel With or Without Trastuzumab in Treating Women With Node-Positive Breast Cancer That Overexpresses HER2), was updated in 2011. We now report the planned definitive overall survival (OS) results from this joint analysis along with updates on the disease-free survival (DFS) end point.
  
  
  METHODS
  In all, 4,046 patients with HER2-positive operable breast cancer were enrolled to receive doxorubicin and cyclophosphamide followed by paclitaxel with or without trastuzumab in both trials. The required number of events for the definitive statistical analysis for OS (710 events) was reached in September 2012. Updated analyses of overall DFS and related subgroups were also performed.
  
  
  RESULTS
  Median time on study was 8.4 years. Adding trastuzumab to chemotherapy led to a 37% relative improvement in OS (hazard ratio [HR], 0.63; 95% CI, 0.54 to 0.73; P < .001) and an increase in 10-year OS rate from 75.2% to 84%. These results were accompanied by an improvement in DFS of 40% (HR, 0.60; 95% CI, 0.53 to 0.68; P < .001) and increase in 10-year DFS rate from 62.2% to 73.7%. All patient subgroups benefited from addition of this targeted anti-HER2 agent.
  
  
  CONCLUSIONS
  The addition of trastuzumab to paclitaxel after doxorubicin and cyclophosphamide in early-stage HER2-positive breast cancer results in a substantial and durable improvement in survival as a result of a sustained marked reduction in cancer recurrence.
authors.affiliation: Edith A. Perez, Gerardo Colon-Otero, the Mayo Clinic, Jacksonville; Eleftherios Mamounas, University of Florida Health Cancer Center-Orlando Health, Orlando, FL; Edward H. Romond, University of Kentucky, Lexington, KY; Vera J. Suman, Mayo Clinic, Rochester, MN; Jong-Hyeon Jeong, Priya Rastogi, University of Pittsburgh; Nancy E. Davidson, University of Pittsburgh Cancer Institute; Norman Wolmark, Allegheny General Hospital, Pittsburgh, PA; George Sledge, Stanford University School of Medicine, Stanford; Silvana Martino, The Angeles Clinic and Research Institute, Santa Monica, CA; Charles E. Geyer Jr, Virginia Commonwealth University Massey Cancer Center, Richmond, VA; Julie Gralow, University of Washington/Seattle Cancer Care Alliance, Seattle, WA; Sandra M. Swain, MedStar Washington Hospital Center, Washington, DC; Eric P. Winer, Dana-Farber Cancer Institute, Boston, MA; Jo Anne Zujewski, National Institutes of Health, Rockville, MD. perez.edith@mayo.edu.
authors.forename: Edith A
authors.initials: EA
authors.lastname: Perez
authors.affiliation: Edith A. Perez, Gerardo Colon-Otero, the Mayo Clinic, Jacksonville; Eleftherios Mamounas, University of Florida Health Cancer Center-Orlando Health, Orlando, FL; Edward H. Romond, University of Kentucky, Lexington, KY; Vera J. Suman, Mayo Clinic, Rochester, MN; Jong-Hyeon Jeong, Priya Rastogi, University of Pittsburgh; Nancy E. Davidson, University of Pittsburgh Cancer Institute; Norman Wolmark, Allegheny General Hospital, Pittsburgh, PA; George Sledge, Stanford University School of Medicine, Stanford; Silvana Martino, The Angeles Clinic and Research Institute, Santa Monica, CA; Charles E. Geyer Jr, Virginia Commonwealth University Massey Cancer Center, Richmond, VA; Julie Gralow, University of Washington/Seattle Cancer Care Alliance, Seattle, WA; Sandra M. Swain, MedStar Washington Hospital Center, Washington, DC; Eric P. Winer, Dana-Farber Cancer Institute, Boston, MA; Jo Anne Zujewski, National Institutes of Health, Rockville, MD.
authors.forename: Edward H
authors.initials: EH
authors.lastname: Romond
authors.affiliation: Edith A. Perez, Gerardo Colon-Otero, the Mayo Clinic, Jacksonville; Eleftherios Mamounas, University of Florida Health Cancer Center-Orlando Health, Orlando, FL; Edward H. Romond, University of Kentucky, Lexington, KY; Vera J. Suman, Mayo Clinic, Rochester, MN; Jong-Hyeon Jeong, Priya Rastogi, University of Pittsburgh; Nancy E. Davidson, University of Pittsburgh Cancer Institute; Norman Wolmark, Allegheny General Hospital, Pittsburgh, PA; George Sledge, Stanford University School of Medicine, Stanford; Silvana Martino, The Angeles Clinic and Research Institute, Santa Monica, CA; Charles E. Geyer Jr, Virginia Commonwealth University Massey Cancer Center, Richmond, VA; Julie Gralow, University of Washington/Seattle Cancer Care Alliance, Seattle, WA; Sandra M. Swain, MedStar Washington Hospital Center, Washington, DC; Eric P. Winer, Dana-Farber Cancer Institute, Boston, MA; Jo Anne Zujewski, National Institutes of Health, Rockville, MD.
authors.forename: Vera J
authors.initials: VJ
authors.lastname: Suman
authors.affiliation: Edith A. Perez, Gerardo Colon-Otero, the Mayo Clinic, Jacksonville; Eleftherios Mamounas, University of Florida Health Cancer Center-Orlando Health, Orlando, FL; Edward H. Romond, University of Kentucky, Lexington, KY; Vera J. Suman, Mayo Clinic, Rochester, MN; Jong-Hyeon Jeong, Priya Rastogi, University of Pittsburgh; Nancy E. Davidson, University of Pittsburgh Cancer Institute; Norman Wolmark, Allegheny General Hospital, Pittsburgh, PA; George Sledge, Stanford University School of Medicine, Stanford; Silvana Martino, The Angeles Clinic and Research Institute, Santa Monica, CA; Charles E. Geyer Jr, Virginia Commonwealth University Massey Cancer Center, Richmond, VA; Julie Gralow, University of Washington/Seattle Cancer Care Alliance, Seattle, WA; Sandra M. Swain, MedStar Washington Hospital Center, Washington, DC; Eric P. Winer, Dana-Farber Cancer Institute, Boston, MA; Jo Anne Zujewski, National Institutes of Health, Rockville, MD.
authors.forename: Jong-Hyeon
authors.initials: JH
authors.lastname: Jeong
authors.affiliation: Edith A. Perez, Gerardo Colon-Otero, the Mayo Clinic, Jacksonville; Eleftherios Mamounas, University of Florida Health Cancer Center-Orlando Health, Orlando, FL; Edward H. Romond, University of Kentucky, Lexington, KY; Vera J. Suman, Mayo Clinic, Rochester, MN; Jong-Hyeon Jeong, Priya Rastogi, University of Pittsburgh; Nancy E. Davidson, University of Pittsburgh Cancer Institute; Norman Wolmark, Allegheny General Hospital, Pittsburgh, PA; George Sledge, Stanford University School of Medicine, Stanford; Silvana Martino, The Angeles Clinic and Research Institute, Santa Monica, CA; Charles E. Geyer Jr, Virginia Commonwealth University Massey Cancer Center, Richmond, VA; Julie Gralow, University of Washington/Seattle Cancer Care Alliance, Seattle, WA; Sandra M. Swain, MedStar Washington Hospital Center, Washington, DC; Eric P. Winer, Dana-Farber Cancer Institute, Boston, MA; Jo Anne Zujewski, National Institutes of Health, Rockville, MD.
authors.forename: George
authors.initials: G
authors.lastname: Sledge
authors.affiliation: Edith A. Perez, Gerardo Colon-Otero, the Mayo Clinic, Jacksonville; Eleftherios Mamounas, University of Florida Health Cancer Center-Orlando Health, Orlando, FL; Edward H. Romond, University of Kentucky, Lexington, KY; Vera J. Suman, Mayo Clinic, Rochester, MN; Jong-Hyeon Jeong, Priya Rastogi, University of Pittsburgh; Nancy E. Davidson, University of Pittsburgh Cancer Institute; Norman Wolmark, Allegheny General Hospital, Pittsburgh, PA; George Sledge, Stanford University School of Medicine, Stanford; Silvana Martino, The Angeles Clinic and Research Institute, Santa Monica, CA; Charles E. Geyer Jr, Virginia Commonwealth University Massey Cancer Center, Richmond, VA; Julie Gralow, University of Washington/Seattle Cancer Care Alliance, Seattle, WA; Sandra M. Swain, MedStar Washington Hospital Center, Washington, DC; Eric P. Winer, Dana-Farber Cancer Institute, Boston, MA; Jo Anne Zujewski, National Institutes of Health, Rockville, MD.
authors.forename: Charles E
authors.initials: CE
authors.lastname: Geyer
authors.affiliation: Edith A. Perez, Gerardo Colon-Otero, the Mayo Clinic, Jacksonville; Eleftherios Mamounas, University of Florida Health Cancer Center-Orlando Health, Orlando, FL; Edward H. Romond, University of Kentucky, Lexington, KY; Vera J. Suman, Mayo Clinic, Rochester, MN; Jong-Hyeon Jeong, Priya Rastogi, University of Pittsburgh; Nancy E. Davidson, University of Pittsburgh Cancer Institute; Norman Wolmark, Allegheny General Hospital, Pittsburgh, PA; George Sledge, Stanford University School of Medicine, Stanford; Silvana Martino, The Angeles Clinic and Research Institute, Santa Monica, CA; Charles E. Geyer Jr, Virginia Commonwealth University Massey Cancer Center, Richmond, VA; Julie Gralow, University of Washington/Seattle Cancer Care Alliance, Seattle, WA; Sandra M. Swain, MedStar Washington Hospital Center, Washington, DC; Eric P. Winer, Dana-Farber Cancer Institute, Boston, MA; Jo Anne Zujewski, National Institutes of Health, Rockville, MD.
authors.forename: Silvana
authors.initials: S
authors.lastname: Martino
authors.affiliation: Edith A. Perez, Gerardo Colon-Otero, the Mayo Clinic, Jacksonville; Eleftherios Mamounas, University of Florida Health Cancer Center-Orlando Health, Orlando, FL; Edward H. Romond, University of Kentucky, Lexington, KY; Vera J. Suman, Mayo Clinic, Rochester, MN; Jong-Hyeon Jeong, Priya Rastogi, University of Pittsburgh; Nancy E. Davidson, University of Pittsburgh Cancer Institute; Norman Wolmark, Allegheny General Hospital, Pittsburgh, PA; George Sledge, Stanford University School of Medicine, Stanford; Silvana Martino, The Angeles Clinic and Research Institute, Santa Monica, CA; Charles E. Geyer Jr, Virginia Commonwealth University Massey Cancer Center, Richmond, VA; Julie Gralow, University of Washington/Seattle Cancer Care Alliance, Seattle, WA; Sandra M. Swain, MedStar Washington Hospital Center, Washington, DC; Eric P. Winer, Dana-Farber Cancer Institute, Boston, MA; Jo Anne Zujewski, National Institutes of Health, Rockville, MD.
authors.forename: Priya
authors.initials: P
authors.lastname: Rastogi
authors.affiliation: Edith A. Perez, Gerardo Colon-Otero, the Mayo Clinic, Jacksonville; Eleftherios Mamounas, University of Florida Health Cancer Center-Orlando Health, Orlando, FL; Edward H. Romond, University of Kentucky, Lexington, KY; Vera J. Suman, Mayo Clinic, Rochester, MN; Jong-Hyeon Jeong, Priya Rastogi, University of Pittsburgh; Nancy E. Davidson, University of Pittsburgh Cancer Institute; Norman Wolmark, Allegheny General Hospital, Pittsburgh, PA; George Sledge, Stanford University School of Medicine, Stanford; Silvana Martino, The Angeles Clinic and Research Institute, Santa Monica, CA; Charles E. Geyer Jr, Virginia Commonwealth University Massey Cancer Center, Richmond, VA; Julie Gralow, University of Washington/Seattle Cancer Care Alliance, Seattle, WA; Sandra M. Swain, MedStar Washington Hospital Center, Washington, DC; Eric P. Winer, Dana-Farber Cancer Institute, Boston, MA; Jo Anne Zujewski, National Institutes of Health, Rockville, MD.
authors.forename: Julie
authors.initials: J
authors.lastname: Gralow
authors.affiliation: Edith A. Perez, Gerardo Colon-Otero, the Mayo Clinic, Jacksonville; Eleftherios Mamounas, University of Florida Health Cancer Center-Orlando Health, Orlando, FL; Edward H. Romond, University of Kentucky, Lexington, KY; Vera J. Suman, Mayo Clinic, Rochester, MN; Jong-Hyeon Jeong, Priya Rastogi, University of Pittsburgh; Nancy E. Davidson, University of Pittsburgh Cancer Institute; Norman Wolmark, Allegheny General Hospital, Pittsburgh, PA; George Sledge, Stanford University School of Medicine, Stanford; Silvana Martino, The Angeles Clinic and Research Institute, Santa Monica, CA; Charles E. Geyer Jr, Virginia Commonwealth University Massey Cancer Center, Richmond, VA; Julie Gralow, University of Washington/Seattle Cancer Care Alliance, Seattle, WA; Sandra M. Swain, MedStar Washington Hospital Center, Washington, DC; Eric P. Winer, Dana-Farber Cancer Institute, Boston, MA; Jo Anne Zujewski, National Institutes of Health, Rockville, MD.
authors.forename: Sandra M
authors.initials: SM
authors.lastname: Swain
authors.affiliation: Edith A. Perez, Gerardo Colon-Otero, the Mayo Clinic, Jacksonville; Eleftherios Mamounas, University of Florida Health Cancer Center-Orlando Health, Orlando, FL; Edward H. Romond, University of Kentucky, Lexington, KY; Vera J. Suman, Mayo Clinic, Rochester, MN; Jong-Hyeon Jeong, Priya Rastogi, University of Pittsburgh; Nancy E. Davidson, University of Pittsburgh Cancer Institute; Norman Wolmark, Allegheny General Hospital, Pittsburgh, PA; George Sledge, Stanford University School of Medicine, Stanford; Silvana Martino, The Angeles Clinic and Research Institute, Santa Monica, CA; Charles E. Geyer Jr, Virginia Commonwealth University Massey Cancer Center, Richmond, VA; Julie Gralow, University of Washington/Seattle Cancer Care Alliance, Seattle, WA; Sandra M. Swain, MedStar Washington Hospital Center, Washington, DC; Eric P. Winer, Dana-Farber Cancer Institute, Boston, MA; Jo Anne Zujewski, National Institutes of Health, Rockville, MD.
authors.forename: Eric P
authors.initials: EP
authors.lastname: Winer
authors.affiliation: Edith A. Perez, Gerardo Colon-Otero, the Mayo Clinic, Jacksonville; Eleftherios Mamounas, University of Florida Health Cancer Center-Orlando Health, Orlando, FL; Edward H. Romond, University of Kentucky, Lexington, KY; Vera J. Suman, Mayo Clinic, Rochester, MN; Jong-Hyeon Jeong, Priya Rastogi, University of Pittsburgh; Nancy E. Davidson, University of Pittsburgh Cancer Institute; Norman Wolmark, Allegheny General Hospital, Pittsburgh, PA; George Sledge, Stanford University School of Medicine, Stanford; Silvana Martino, The Angeles Clinic and Research Institute, Santa Monica, CA; Charles E. Geyer Jr, Virginia Commonwealth University Massey Cancer Center, Richmond, VA; Julie Gralow, University of Washington/Seattle Cancer Care Alliance, Seattle, WA; Sandra M. Swain, MedStar Washington Hospital Center, Washington, DC; Eric P. Winer, Dana-Farber Cancer Institute, Boston, MA; Jo Anne Zujewski, National Institutes of Health, Rockville, MD.
authors.forename: Gerardo
authors.initials: G
authors.lastname: Colon-Otero
authors.affiliation: Edith A. Perez, Gerardo Colon-Otero, the Mayo Clinic, Jacksonville; Eleftherios Mamounas, University of Florida Health Cancer Center-Orlando Health, Orlando, FL; Edward H. Romond, University of Kentucky, Lexington, KY; Vera J. Suman, Mayo Clinic, Rochester, MN; Jong-Hyeon Jeong, Priya Rastogi, University of Pittsburgh; Nancy E. Davidson, University of Pittsburgh Cancer Institute; Norman Wolmark, Allegheny General Hospital, Pittsburgh, PA; George Sledge, Stanford University School of Medicine, Stanford; Silvana Martino, The Angeles Clinic and Research Institute, Santa Monica, CA; Charles E. Geyer Jr, Virginia Commonwealth University Massey Cancer Center, Richmond, VA; Julie Gralow, University of Washington/Seattle Cancer Care Alliance, Seattle, WA; Sandra M. Swain, MedStar Washington Hospital Center, Washington, DC; Eric P. Winer, Dana-Farber Cancer Institute, Boston, MA; Jo Anne Zujewski, National Institutes of Health, Rockville, MD.
authors.forename: Nancy E
authors.initials: NE
authors.lastname: Davidson
authors.affiliation: Edith A. Perez, Gerardo Colon-Otero, the Mayo Clinic, Jacksonville; Eleftherios Mamounas, University of Florida Health Cancer Center-Orlando Health, Orlando, FL; Edward H. Romond, University of Kentucky, Lexington, KY; Vera J. Suman, Mayo Clinic, Rochester, MN; Jong-Hyeon Jeong, Priya Rastogi, University of Pittsburgh; Nancy E. Davidson, University of Pittsburgh Cancer Institute; Norman Wolmark, Allegheny General Hospital, Pittsburgh, PA; George Sledge, Stanford University School of Medicine, Stanford; Silvana Martino, The Angeles Clinic and Research Institute, Santa Monica, CA; Charles E. Geyer Jr, Virginia Commonwealth University Massey Cancer Center, Richmond, VA; Julie Gralow, University of Washington/Seattle Cancer Care Alliance, Seattle, WA; Sandra M. Swain, MedStar Washington Hospital Center, Washington, DC; Eric P. Winer, Dana-Farber Cancer Institute, Boston, MA; Jo Anne Zujewski, National Institutes of Health, Rockville, MD.
authors.forename: Eleftherios
authors.initials: E
authors.lastname: Mamounas
authors.affiliation: Edith A. Perez, Gerardo Colon-Otero, the Mayo Clinic, Jacksonville; Eleftherios Mamounas, University of Florida Health Cancer Center-Orlando Health, Orlando, FL; Edward H. Romond, University of Kentucky, Lexington, KY; Vera J. Suman, Mayo Clinic, Rochester, MN; Jong-Hyeon Jeong, Priya Rastogi, University of Pittsburgh; Nancy E. Davidson, University of Pittsburgh Cancer Institute; Norman Wolmark, Allegheny General Hospital, Pittsburgh, PA; George Sledge, Stanford University School of Medicine, Stanford; Silvana Martino, The Angeles Clinic and Research Institute, Santa Monica, CA; Charles E. Geyer Jr, Virginia Commonwealth University Massey Cancer Center, Richmond, VA; Julie Gralow, University of Washington/Seattle Cancer Care Alliance, Seattle, WA; Sandra M. Swain, MedStar Washington Hospital Center, Washington, DC; Eric P. Winer, Dana-Farber Cancer Institute, Boston, MA; Jo Anne Zujewski, National Institutes of Health, Rockville, MD.
authors.forename: Jo Anne
authors.initials: JA
authors.lastname: Zujewski
authors.affiliation: Edith A. Perez, Gerardo Colon-Otero, the Mayo Clinic, Jacksonville; Eleftherios Mamounas, University of Florida Health Cancer Center-Orlando Health, Orlando, FL; Edward H. Romond, University of Kentucky, Lexington, KY; Vera J. Suman, Mayo Clinic, Rochester, MN; Jong-Hyeon Jeong, Priya Rastogi, University of Pittsburgh; Nancy E. Davidson, University of Pittsburgh Cancer Institute; Norman Wolmark, Allegheny General Hospital, Pittsburgh, PA; George Sledge, Stanford University School of Medicine, Stanford; Silvana Martino, The Angeles Clinic and Research Institute, Santa Monica, CA; Charles E. Geyer Jr, Virginia Commonwealth University Massey Cancer Center, Richmond, VA; Julie Gralow, University of Washington/Seattle Cancer Care Alliance, Seattle, WA; Sandra M. Swain, MedStar Washington Hospital Center, Washington, DC; Eric P. Winer, Dana-Farber Cancer Institute, Boston, MA; Jo Anne Zujewski, National Institutes of Health, Rockville, MD.
authors.forename: Norman
authors.initials: N
authors.lastname: Wolmark
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000737:chemistry / Q000188:drug therapy* / Q000401:mortality; D017024:Chemotherapy, Adjuvant; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008875:Middle Aged; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis*; D000068878:Trastuzumab
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab; C508053:ERBB2 protein, human