title: Detection of HER2-Positive Metastases in Patients with HER2-Negative Primary Breast Cancer Using 89Zr-Trastuzumab PET/CT.
abstract: Our objective was to determine whether imaging with a human epidermal growth factor receptor 2 (HER2)-targeted PET tracer can detect HER2-positive metastases in patients with HER2-negative primary breast cancer.
  
  
  METHODS
  Patients with HER2-negative primary breast cancer and evidence of distant metastases were enrolled in an Institutional Review Board-approved prospective clinical trial. Archived pathologic samples from the patient's primary breast cancer were retested to confirm HER2-negative disease. Patients with confirmed HER2-negative primary breast cancer underwent89Zr-trastuzumab PET/CT to screen for89Zr-trastuzumab metastases. Metastases avid for89Zr-trastuzumab by PET/CT were biopsied and pathologically examined to define HER2 status. Patients with pathologically proven HER2-positive metastases subsequently received off-protocol HER2-targeted therapy to evaluate treatment response.
  
  
  RESULTS
  Nine patients were enrolled, all of whom had pathologic retesting that confirmed HER2-negative primary breast cancer. Five demonstrated suggestive foci on89Zr-trastuzumab PET/CT. Of these 5 patients, 2 had biopsy-proven HER2-positive metastases and went on to benefit from HER2-targeted therapy. In the other 3 patients, biopsy showed no evidence of HER2-positive disease, and their foci on89Zr-trastuzumab PET were considered false-positive.
  
  
  CONCLUSIONS
  In this proof-of-concept study, we demonstrated that89Zr-trastuzmab PET/CT detects unsuspected HER2-positive metastases in patients with HER2-negative primary breast cancer. Although these are only initial results in a small sample, they are a proof of the concept that HER2-targeted imaging can identify additional candidates for HER2-targeted therapy. More specific HER2-targeted agents will be needed for clinical use.
authors.affiliation: Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, New York Department of Radiology, Weill Cornell Medical College, New York, New York ulanerg@mskcc.org.
authors.forename: Gary A
authors.initials: GA
authors.lastname: Ulaner
authors.affiliation: Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York Department of Medicine, Weill Cornell Medical College, New York, New York.
authors.forename: David M
authors.initials: DM
authors.lastname: Hyman
authors.affiliation: Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, New York.
authors.forename: Dara S
authors.initials: DS
authors.lastname: Ross
authors.affiliation: Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, New York.
authors.forename: Adriana
authors.initials: A
authors.lastname: Corben
authors.affiliation: Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York Department of Medicine, Weill Cornell Medical College, New York, New York.
authors.forename: Sarat
authors.initials: S
authors.lastname: Chandarlapaty
authors.affiliation: Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York Department of Medicine, Weill Cornell Medical College, New York, New York.
authors.forename: Shari
authors.initials: S
authors.lastname: Goldfarb
authors.affiliation: Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York Department of Medicine, Weill Cornell Medical College, New York, New York.
authors.forename: Heather
authors.initials: H
authors.lastname: McArthur
authors.affiliation: Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, New York Department of Radiology, Weill Cornell Medical College, New York, New York.
authors.forename: Joseph P
authors.initials: JP
authors.lastname: Erinjeri
authors.affiliation: Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, New York Department of Radiology, Weill Cornell Medical College, New York, New York.
authors.forename: Stephen B
authors.initials: SB
authors.lastname: Solomon
authors.affiliation: Department of Neuroscience Biomarkers, Janssen R&D, San Diego, California; and.
authors.forename: Hartmuth
authors.initials: H
authors.lastname: Kolb
authors.affiliation: Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, New York Department of Radiology, Weill Cornell Medical College, New York, New York.
authors.forename: Serge K
authors.initials: SK
authors.lastname: Lyashchenko
authors.affiliation: Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, New York Department of Radiology, Weill Cornell Medical College, New York, New York Program in Molecular Pharmacology, Memorial Sloan Kettering Cancer Center, New York, New York.
authors.forename: Jason S
authors.initials: JS
authors.lastname: Lewis
authors.affiliation: Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, New York Department of Radiology, Weill Cornell Medical College, New York, New York.
authors.forename: Jorge A
authors.initials: JA
authors.lastname: Carrasquillo
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D061067:Antibodies, Monoclonal, Humanized; D001943:Breast Neoplasms / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000473:pathology*; D005260:Female; D006801:Humans; D008875:Middle Aged; D009362:Neoplasm Metastasis; D000072078:Positron Emission Tomography Computed Tomography; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D018719:Erb-b2 Receptor Tyrosine Kinases; C571668:zirconium-89-trastuzumab
keywords: HER2; PET/CT; breast; molecular imaging; oncology; trastuzumab