PT - JOURNAL ARTICLE AU - Gary Ulaner AU - David Hyman AU - Dara Ross AU - Adriana Corben AU - Sarat Chandarlapaty AU - Shari Goldfarb AU - Mcarthur Heather AU - Joseph Erinjeri AU - Stephen Solomon AU - Hartmuth Kolb AU - Serge Lyashchenko AU - Jason Lewis AU - Jorge Carrasquillo TI - Detection of HER2-positive metastases in patients with HER2-negative primary breast cancer using <sup>89</sup>Zr-DFO-trastuzumab PET/CT <strong/> DP - 2016 May 01 TA - Journal of Nuclear Medicine PG - 586--586 VI - 57 IP - supplement 2 4099 - http://jnm.snmjournals.org/content/57/supplement_2/586.short 4100 - http://jnm.snmjournals.org/content/57/supplement_2/586.full SO - J Nucl Med2016 May 01; 57 AB - 586Objectives To determine if imaging with a HER2-targeting PET tracer can detect HER2-positive metastases in patients with HER2-negative primary breast cancer.Methods Patients with HER2-negative primary breast cancer, defined according to ASCO guidelines, and evidence of distant metastases were enrolled in an IRB-approved prospective clinical trial. Archived pathology from the patient’s primary breast cancer was retested to confirm HER2-negative disease. Patients with confirmed HER2-negative primary breast cancer underwent 89Zr-DFO-trastuzumab PET/CT to screen for 89Zr-DFO-trastuzumab metastases. Metastases avid for 89Zr-DFO-trastuzumab by PET/CT were biopsied and pathologically examined to define HER2 status. Patients with pathologically proven HER2-positive metastases subsequently received 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 suspicious foci on 89Zr-DFO-trastuzumab PET/CT. Of these five with suspicious foci, two had 89Zr-DFO-trastuzmab directed biopsy that confirmed HER2-positive metastases and went on to benefit from HER2 targeted therapy. Three of the five patients with suspicious foci had biopsy proven metastatic disease without evidence of HER2-positive disease, and were considered false positive for HER2.Conclusions In this proof-of-concept study, we demonstrate that 89Zr-DFO-trastuzmab PET/CT detects unsuspected HER2-positive metastases in patients with HER2-negative primary breast cancer. While these are only initial results in a small sample, it is a proof of concept that HER2-targeted imaging can identify additional candidates for HER2-targeted therapy. 89Zr-DFO-trastuzmab also localized in metastatic sites not considered HER2 positive by defined criteria. Future studies could be performed to assess whether these “false positive” would benefit from trastuzumab therapy. This study is supported by Department of Defense Breast Cancer Research Program Breakthrough Award BC132676. The authors gratefully acknowledge the MSKCC Radiochemistry and Molecular Imaging Probe Core (NIH grant P30 CA08748), the Center for Targeted Radioimmunotherapy of the Ludwig Center for Cancer Immunotherapy, and the Geoffrey Beene Cancer Center at MSKCC for additional support.