89Zr-Trastuzumab PET/CT for Detection of Human Epidermal Growth Factor Receptor 2-Positive Metastases in Patients With Human Epidermal Growth Factor Receptor 2-Negative Primary Breast Cancer

Purpose The aim of this study was to determine if imaging with Zr-89-trastuzumab, a human epidermal growth factor receptor 2 (HER2)-targeting PET tracer, can detect HER2-positive metastases in patients with HER2-negative primary breast cancer. Methods As part of an institutional review board-approved, prospective clinical trial of Zr-89-trastuzumab PET/CT (ClinicalTrials.gov identifier NCT02286843), a second group of 11 patients with HER2-negative primary breast cancer and known metastatic disease were recruited. Patients with confirmed HER2-negative primary breast cancer underwent Zr-89-trastuzumab PET/CT to screen for Zr-89-trastuzumab-avid lesions suggestive of unsuspected HER2-positive metastases. Zr-89-trastuzumab-avid lesions on PET/CT were biopsied and pathologically examined to determine HER2 status. Results All 11 patients had confirmed HER2-negative primary breast cancer. Four patients demonstrated suspicious foci on Zr-89-trastuzumab PET/CT. Of these 4 patients, 1 patient had biopsy-proven HER2-positive metastases. The other 3 patients with suspicious Zr-89-trastuzumab-avid foci had biopsy demonstrating a metastasis that was HER2-negative and were considered false-positive Zr-89-trastuzumab PET foci. Combined with a published report of the first 9 patients, there have been a total of 20 HER2-negative primary breast cancer patients, with 3 patients (15%) having pathologically confirmed HER2-positive distant metastases and 6 (30%) with suspicious Zr-89-trastuzumab-avid foci that were HER2-negative on pathology, which were thus considered false-positive Zr-89-trastuzumab findings. Conclusions This second group of patients confirms the proof of concept that Zr-89-trastuzumab PET/CT detects unsuspected HER2-positive metastases in a subset of patients with HER2-negtive primary breast cancer. False-positive Zr-89-trastuzumab-avid foci present a challenge to using this tracer.