title: Impact of c-MYC protein expression on outcome of patients with early-stage HER2+ breast cancer treated with adjuvant trastuzumab NCCTG (alliance) N9831.
abstract: OBJECTIVE
  This study investigated the association between tumor MYC protein expression and disease-free survival (DFS) of patients randomized to receive chemotherapy alone (Arm A) or chemotherapy with sequential (Arm B) or concurrent trastuzumab (Arm C) in the N9831 (Alliance) adjuvant HER2(+) trastuzumab breast cancer trial.
  
  
  METHODS
  This analysis included 1,736 patients randomized to Arms A, B, and C on N9831. Nuclear MYC protein expression was determined in tissue microarray sections containing three biopsies per patient or whole tissue sections using standard immunohistochemistry (clone 9E10). A tumor was considered positive for MYC protein overexpression (MYC(+)) if the nuclear 3+ staining percentage was more than 30%.
  
  
  RESULTS
  Five hundred and seventy-four (33%) tumors were MYC(+). MYC(+) was associated with hormone receptor positivity (χ(2), P = 0.006), tumors 2 cm or more (χ(2), P = 0.02), and a higher rate of nodal positivity (χ(2), P < 0.001). HRs for DFS (median follow-up: 6.1 years) for Arm C versus A were 0.52 (P = 0.006) and 0.65 (P = 0.006) for patients with MYC(+) and MYC(-) tumors, respectively (P(interaction) = 0.40). For Arm B versus A, HRs for patients with MYC(+) and MYC(-) tumors were 0.79 (P = 0.21) and 0.74 (P = 0.04), respectively (P(interaction) = 0.71). For Arm C versus B, HRs for patients with MYC(+) and MYC(-) tumors were 0.56 (P = 0.02) and 0.89 (P = 0.49), respectively (P(interaction) = 0.17).
  
  
  CONCLUSIONS
  Our data do not support an impact of tumor MYC protein expression on differential benefit from adjuvant trastuzumab.
authors: Authors' Affiliations: Section of Biostatistics; Division of Anatomic Pathology, Mayo Clinic, Scottsdale, Arizona; Division of Experimental Pathology, Department of Laboratory Medicine and Pathology; Division of Biomedical Statistics and Informatics and Medical Oncology, Mayo Clinic, Rochester, Minnesota; Division of Anatomic Pathology and Hematology/Oncology, Mayo Clinic, Jacksonville, Florida; Division of Hematology/Oncology, University of Pittsburgh Cancer Institute and UPMC Cancer Center, Pittsburgh, Pennsylvania; The Angeles Clinic and Research Institute, Santa Monica, California; Indiana University Medical Center Cancer Pavilion, Indianapolis, Indiana; Division of Hematology/Oncology, Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire; Oncology Associates of Cedar Rapids, Cedar Rapids, Iowa; Seattle Cancer Care Alliance, Seattle, Washington; and Case Western Reserve University, Cleveland, Ohio.
authors: Amylou C
authors: AC
authors: Dueck
authors: Monica M
authors: MM
authors: Reinholz
authors: Xochiquetzal J
authors: XJ
authors: Geiger
authors: Kathleen
authors: K
authors: Tenner
authors: Karla
authors: K
authors: Ballman
authors: Robert B
authors: RB
authors: Jenkins
authors: Darren
authors: D
authors: Riehle
authors: Beiyun
authors: B
authors: Chen
authors: Ann E
authors: AE
authors: McCullough
authors: Nancy E
authors: NE
authors: Davidson
authors: Silvana
authors: S
authors: Martino
authors: George W
authors: GW
authors: Sledge
authors: Peter A
authors: PA
authors: Kaufman
authors: Leila A
authors: LA
authors: Kutteh
authors: Julie
authors: J
authors: Gralow
authors: Lyndsay N
authors: LN
authors: Harris
authors: James N
authors: JN
authors: Ingle
authors: Wilma L
authors: WL
authors: Lingle
authors: Edith A
authors: EA
authors: Perez
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000401:mortality* / Q000473:pathology; D017024:Chemotherapy, Adjuvant; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D009367:Neoplasm Staging; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D012307:Risk Factors; D000068878:Trastuzumab; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D016271:Proto-Oncogene Proteins c-myc; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab
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