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J Nucl Med. 2016 Oct;57(10):1523-1528. Epub 2016 May 5.

Detection of HER2-Positive Metastases in Patients with HER2-Negative Primary Breast Cancer Using 89Zr-Trastuzumab PET/CT.

Author information

1
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.
2
Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York Department of Medicine, Weill Cornell Medical College, New York, New York.
3
Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, New York.
4
Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, New York Department of Radiology, Weill Cornell Medical College, New York, New York.
5
Department of Neuroscience Biomarkers, Janssen R&D, San Diego, California; and.
6
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.

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.

KEYWORDS:

HER2; PET/CT; breast; molecular imaging; oncology; trastuzumab

PMID:
27151988
PMCID:
PMC5050126
DOI:
10.2967/jnumed.115.172031
[Indexed for MEDLINE]
Free PMC Article

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