title: Concordance between local and central laboratory HER2 testing in the breast intergroup trial N9831.
abstract: The efficacy of trastuzumab for metastases coupled with the relatively poor prognosis of patients with node-positive, HER2-positive breast cancer has led to the evaluation of trastuzumab as an adjuvant therapy. A prospective, randomized, three-arm, phase III trial is being conducted by the Breast Intergroup (N9831) for women with primary, operable, histologically confirmed, node-positive breast carcinoma that strongly overexpresses (3+) HER2 protein and/or displays HER2/neu gene amplification, as determined by local laboratory testing. The protocol requires confirmatory central testing of HER2 status using the HercepTest immunohistochemistry and the Vysis PathVysion fluorescence in situ hybridization (FISH) assays. Tumor specimens from the first 119 patients enrolled in N9831 were centrally tested; 74% were found to be HercepTest 3+ and 66% were found to have HER2 gene amplification. Only six of nine (67%) of the specimens submitted by local laboratories as FISH positive could be confirmed by central assays. The concordance for central HercepTest and central FISH assays was 92%. The poor concordance (74%) between local and central testing for HER2 status has led to modifications in the eligibility criteria for N9831.
authors.affiliation: Mayo Clinic and Mayo Foundation, Rochester, MN, USA.
authors.forename: Patrick C
authors.initials: PC
authors.lastname: Roche
authors.forename: Vera J
authors.initials: VJ
authors.lastname: Suman
authors.forename: Robert B
authors.initials: RB
authors.lastname: Jenkins
authors.forename: Nancy E
authors.initials: NE
authors.lastname: Davidson
authors.forename: Silvana
authors.initials: S
authors.lastname: Martino
authors.forename: Peter A
authors.initials: PA
authors.lastname: Kaufman
authors.forename: Ferdinand K
authors.initials: FK
authors.lastname: Addo
authors.forename: Bronagh
authors.initials: B
authors.lastname: Murphy
authors.forename: James N
authors.initials: JN
authors.lastname: Ingle
authors.forename: Edith A
authors.initials: EA
authors.lastname: Perez
mesh_terms: D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000175:diagnosis / Q000188:drug therapy / Q000378:metabolism*; D017024:Chemotherapy, Adjuvant; D017326:Clinical Trials, Phase III as Topic / Q000379:methods*; D000075202:Contraindications; D003951:Diagnostic Errors; D005260:Female; D005784:Gene Amplification; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D018579:Patient Selection; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis* / Q000235:genetics; D015203:Reproducibility of Results; D000068878:Trastuzumab
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab