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

Abstract

Purpose: The aim of this study was to determine if imaging with Zr-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-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-trastuzumab PET/CT to screen for Zr-trastuzumab-avid lesions suggestive of unsuspected HER2-positive metastases. Zr-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-trastuzumab PET/CT. Of these 4 patients, 1 patient had biopsy-proven HER2-positive metastases. The other 3 patients with suspicious Zr-trastuzumab-avid foci had biopsy demonstrating a metastasis that was HER2-negative and were considered false-positive Zr-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-trastuzumab-avid foci that were HER2-negative on pathology, which were thus considered false-positive Zr-trastuzumab findings.

Conclusions: This second group of patients confirms the proof of concept that Zr-trastuzumab PET/CT detects unsuspected HER2-positive metastases in a subset of patients with HER2-negtive primary breast cancer. False-positive Zr-trastuzumab-avid foci present a challenge to using this tracer.

Conflict of interest statement

Conflict of Interest Disclosure Statement: The authors have no conflicts of interest to declare.

Figures

Figure 1

47-year-old woman with primary ER-positive, HER2-negative invasive ductal breast carcinoma and known metastases in the liver, nodes, and pleura. (A) Axial CT and PET images from a contrast-enhanced FDG PET/CT through the chest demonstrates FDG-avid right pleural masses (SUVmax 6.0, arrows). (B) Axial CT and PET images from a non-contrast-enhanced 89Zr-trastuzumab PET/CT at the same level demonstrates 89Zr-trastuzumab avidity in the pleural lesions (SUVmax 6.9, arrows).

Figure 2

51-year-old woman with primary ER-positive, HER2-negative invasive ductal breast carcinoma. (A) FDG PET MIP demonstrates multiple FDG-avid metastases, which correspond to lesions in the lung (arrow), nodes (arrowhead), and bone (curved arrow). (B) Axial CT and PET images from a contrast-enhanced FDG PET/CT through the chest, displayed in lung CT windows, demonstrate an FDG-avid left lung mass (SUVmax 7.3, arrow). (C) 89Zr-trastuzumab PET MIP demonstrates physiologic tracer in the blood pool, liver, and bowel, as well as a suspicious 89Zr-trastuzumab-avid focus in the upper chest (arrow). (D) Axial CT and PET images from a non-contrast-enhanced 89Zr-trastuzumab PET/CT demonstrate that the suspicious 89Zr-trastuzumab-avid focus corresponds to the left lung mass (SUVmax 11.3, arrowhead).

Figure 3

58-year-old woman with primary ER-positive, HER2-negative invasive ductal breast carcinoma and known metastases in the bone, liver, and nodes. (A) Axial CT and PET images from a non-contrast-enhanced FDG PET/CT through the abdomen demonstrates an FDG-avid liver metastasis (SUVmax 5.6, arrows). (B) Axial CT and PET images from a non-contrast-enhanced 89Zr-trastuzumab PET/CT at the same level demonstrates 89Zr-trastuzumab avidity in the liver metastasis (SUVmax 15.7, arrows).