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Could HER2 Heterogeneity Open New Therapeutic Options in Patients with HER2- Primary Breast Cancer?

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[Technical Report, Annual Report]

Corporate Author:

Memorial Sloan Kettering Cancer Center

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The purpose of this study is to determine if targeted imaging with a HER2-targeting PET tracer can detect HER2-positive metastases inpatients with HER2-negative primary breast cancer. 43 of a potential 50 patients have been accrued to the trial. The first phase of the trial composed of 23 patients with HER2-negative primary breast cancer who were imaged with 89Zr-trastuzumab PETCT. In 3 of these 23patients, 89Zr-trastuzumab showed biopsy-proven HER2-positive metastases in patients with presumed HER2-negative primary disease, demonstrating the proof-of-concept that targeted imaging may help identify patients eligible for targeted therapies. However, in 6 additional patients, 89Zr-trastuzumab-avid foci were HER2-negative on pathology, and these false-positives limit the utility of 89Zrtrastuzumab imaging. A more specific radiotracer was needed. The second phase of the trial was first-in-human 89Zr-pertuzumab PETCT, as a potentially more specific radiotracer. Six patients with HER2-positive metastatic breast cancer were imaged with 89Zr-pertuzumab PETCT, demonstrating safety, dosimetry, and effectiveness of 89Zr-pertuzumab to image HER2-positive disease. The third phase of the trial is 89Zr-pertuzumab PETCT in patients with HER2-negative primary breast cancer, to identify unsuspected HER2-positive metastases. 14 patients have been accrued, with one patient demonstrating HER2-positive metastases. Three manuscripts have been published on this work PMID 29146695, 28872549, 27151988, and a final manuscript will be prepared at its conclusion.


Subject Categories:

  • Medicine and Medical Research

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[A, Approved For Public Release]