title: Predictability of adjuvant trastuzumab benefit in N9831 patients using the ASCO/CAP HER2-positivity criteria.
abstract: The 2007 American Society of Clinical Oncology and College of American Pathologists (ASCO/CAP) joint guidelines defined criteria for HER2 positivity of tumors that modified those of the US Food and Drug Administration (FDA), causing some confusion and uncertainty among clinicians. Using data from the HER2-positive breast cancer adjuvant trial N9831, we compared eligibility for patients who met both criteria, and disease-free survival (DFS) was assessed by Cox proportional hazards regression. The number of patients in the N9831 trial retrospectively eligible for trastuzumab therapy was decreased when ASCO/CAP criteria vs FDA criteria were applied to immunohistochemistry and/or fluorescence in situ hybridization results (107 [3.7%] of 2904 patients with immunohistochemistry results, 37 [1.3%] of 2809 patients with fluorescence in situ hybridization results, and 47 [1.7%] of 2809 patients with both results). Improvement in DFS was similar among patients treated with trastuzumab under either set of criteria (concurrent trastuzumab and chemotherapy compared with chemotherapy alone: by ASCO/CAP criteria, hazard ratio of DFS = 0.59, 95% confidence interval = 0.48 to 0.73; by FDA criteria but not ASCO/CAP criteria, hazard ratio = 0.60, 95% confidence interval = 0.12 to 3.13; number needed to treat to prevent one additional DFS event at 5 years: 10 and 11.2 patients, respectively). Following the 2007 ASCO/CAP criteria for HER2 positivity would negate the option of potentially life-saving trastuzumab therapy for a small but meaningful group of patients. We recommend using FDA-approved HER2 criteria for therapeutic decision making.
authors.affiliation: Mayo Clinic, Jacksonville, FL 32224, USA. perez.edith@mayo.edu
authors.forename: Edith A
authors.initials: EA
authors.lastname: Perez
authors.forename: Amylou C
authors.initials: AC
authors.lastname: Dueck
authors.forename: Ann E
authors.initials: AE
authors.lastname: McCullough
authors.forename: Monica M
authors.initials: MM
authors.lastname: Reinholz
authors.forename: Kathleen S
authors.initials: KS
authors.lastname: Tenner
authors.forename: Nancy E
authors.initials: NE
authors.lastname: Davidson
authors.forename: Julie
authors.initials: J
authors.lastname: Gralow
authors.forename: Lyndsay N
authors.initials: LN
authors.lastname: Harris
authors.forename: Leila A
authors.initials: LA
authors.lastname: Kutteh
authors.forename: David W
authors.initials: DW
authors.lastname: Hillman
authors.forename: Robert B
authors.initials: RB
authors.lastname: Jenkins
authors.forename: Beiyun
authors.initials: B
authors.lastname: Chen
mesh_terms: D000328:Adult; D000368:Aged; D061067:Antibodies, Monoclonal, Humanized / Q000494:pharmacology / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000032:analysis*; D001943:Breast Neoplasms / Q000737:chemistry* / Q000188:drug therapy* / Q000401:mortality; D017024:Chemotherapy, Adjuvant; D015986:Confounding Factors, Epidemiologic; D018572:Disease-Free Survival; D005188:False Negative Reactions; D005189:False Positive Reactions; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D008495:Medical Oncology / Q000379:methods / Q000592:standards; D008875:Middle Aged; D016017:Odds Ratio; D016016:Proportional Hazards Models; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis* / Q000235:genetics; D000068878:Trastuzumab
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D014408:Biomarkers, Tumor; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab