title: Intrinsic Subtype and Therapeutic Response Among HER2-Positive Breaty st Tumors from the NCCTG (Alliance) N9831 Trial.
abstract: Genomic data from human epidermal growth factor receptor 2-positive (HER2+) tumors were analyzed to assess the association between intrinsic subtype and clinical outcome in a large, well-annotated patient cohort.
  
  
  
  Samples from the NCCTG (Alliance) N9831 trial were analyzed using the Prosigna algorithm on the NanoString platform to define intrinsic subtype, risk of recurrence scores, and risk categories for 1392 HER2+ tumors. Subtypes were evaluated for recurrence-free survival (RFS) using Kaplan-Meier and Cox model analysis following adjuvant chemotherapy (n = 484) or chemotherapy plus trastuzumab (n = 908). All statistical tests were two-sided.
  
  
  
  Patients with HER2+ tumors from N9831 were primarily scored as HER2-enriched (72.1%). These individuals received statistically significant benefit from trastuzumab (hazard ratio [HR] = 0.68, 95% confidence interval [CI] = 0.52 to 0.89, P = .005), as did the patients (291 of 1392) with luminal-type tumors (HR = 0.52, 95% CI = 0.32 to 0.85, P = .01). Patients with basal-like tumors (97 of 1392) did not have statistically significantly better RFS when treated with trastuzumab and chemotherapy compared with chemotherapy alone (HR = 1.06, 95% CI = 0.53 to 2.13, P = .87).
  
  
  
  The majority of clinically defined HER2-positive tumors were classified as HER2-enriched or luminal using the Prosigna algorithm. Intrinsic subtype alone cannot replace conventional histopathological evaluation of HER2 status because many tumors that are classified as luminal A or luminal B will benefit from adjuvant trastuzumab if that subtype is accompanied by HER2 overexpression. However, among tumors that overexpress HER2, we speculate that assessment of intrinsic subtype may influence treatment, particularly with respect to evaluating alternative therapeutic approaches for that subset of HER2-positive tumors of the basal-like subtype.
authors: Division of Hematology/Oncology, Department of Medicine, Mayo Clinic Comprehensive Cancer Center, Mayo Clinic, Jacksonville, FL, USA.|Department of Cancer Biology, Mayo Clinic Comprehensive Cancer Center, Mayo Clinic, Jacksonville, FL, USA.
authors: Edith A
authors: EA
authors: Perez
authors: Division of Biostatistics and Bioinformatics, Department of Health Science Research, Mayo Clinic Comprehensive Cancer Center, Mayo Clinic, Rochester, MN, USA.
authors: Karla V
authors: KV
authors: Ballman
authors: Nanostring, Inc., Seattle, WA , USA.
authors: Afshin
authors: A
authors: Mashadi-Hossein
authors: Division of Biostatistics and Bioinformatics, Department of Health Science Research, Mayo Clinic Comprehensive Cancer Center, Mayo Clinic, Rochester, MN, USA.
authors: Kathleen S
authors: KS
authors: Tenner
authors: Department of Cancer Biology, Mayo Clinic Comprehensive Cancer Center, Mayo Clinic, Jacksonville, FL, USA.
authors: Jennifer M
authors: JM
authors: Kachergus
authors: Department of Cancer Biology, Mayo Clinic Comprehensive Cancer Center, Mayo Clinic, Jacksonville, FL, USA.
authors: Nadine
authors: N
authors: Norton
authors: Department of Cancer Biology, Mayo Clinic Comprehensive Cancer Center, Mayo Clinic, Jacksonville, FL, USA.
authors: Brian M
authors: BM
authors: Necela
authors: Department of Cancer Biology, Mayo Clinic Comprehensive Cancer Center, Mayo Clinic, Jacksonville, FL, USA.
authors: Jennifer M
authors: JM
authors: Carr
authors: Nanostring, Inc., Seattle, WA , USA.
authors: Sean
authors: S
authors: Ferree
authors: Departments of Genetics and Pathology & Laboratory Medicine, Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC, USA.
authors: Charles M
authors: CM
authors: Perou
authors: Genonic Health, Inc., Redwood, CA, USA.
authors: Frederick
authors: F
authors: Baehner
authors: Departments of Genetics and Pathology & Laboratory Medicine, Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC, USA.|Clinical Trials and Statistics Unit, The Institute of Cancer Research, London, UK.
authors: Maggie Chon U
authors: MC
authors: Cheang
authors: Department of Cancer Biology, Mayo Clinic Comprehensive Cancer Center, Mayo Clinic, Jacksonville, FL, USA.
authors: E Aubrey
authors: EA
authors: Thompson
mesh_terms: D000465:Algorithms; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000145:classification / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D017024:Chemotherapy, Adjuvant; D003520:Cyclophosphamide / Q000008:administration & dosage; D018572:Disease-Free Survival; D004317:Doxorubicin / Q000008:administration & dosage; D005260:Female; D006801:Humans; D017239:Paclitaxel / Q000008:administration & dosage; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis / Q000235:genetics*; D000068878:Trastuzumab / Q000008:administration & dosage; D047368:Tumor Burden
chemical_list: D003520:Cyclophosphamide; D004317:Doxorubicin; D017239:Paclitaxel; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab; C508053:ERBB2 protein, human