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 underwent 89Zr-trastuzumab PET/CT to screen for 89Zr-trastuzumab metastases. Metastases avid for 89Zr-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 on 89Zr-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 on 89Zr-trastuzumab PET were considered false-positive.

CONCLUSION:

In this proof-of-concept study, we demonstrated that 89Zr-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: Gary A Ulaner, David M Hyman, Dara S Ross, Adriana Corben, Sarat Chandarlapaty, Shari Goldfarb, Heather McArthur, Joseph P Erinjeri, Stephen B Solomon, Hartmuth Kolb, Serge K Lyashchenko, Jason S Lewis, Jorge A Carrasquillo
• Journal: Journal of nuclear medicine : official publication, Society of Nuclear Medicine (J Nucl Med) Vol. 57 Issue 10 Pg. 1523-1528 (Oct 2016) ISSN: 1535-5667 [Electronic] United States
• PMID: 27151988 (Publication Type: Clinical Trial, Journal Article)
• Copyright: © 2016 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

Chemical References

• Antibodies, Monoclonal, Humanized
• zirconium-89-trastuzumab
• Receptor, ErbB-2

Topics

• Adult
• Aged
• Aged, 80 and over
• Antibodies, Monoclonal, Humanized
• Breast Neoplasms (diagnostic imaging, metabolism, pathology)
• Female
• Humans
• Middle Aged
• Neoplasm Metastasis
• Positron Emission Tomography Computed Tomography
• Receptor, ErbB-2 (metabolism)