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Evaluation of [89Zr]trastuzumab-PET/CT in differentiating HER2-positive from HER2-negative breast cancer

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Abstract

Purpose

To evaluate whether tumor uptake of [89Zr]trastuzumab can distinguish HER2-positive from HER2-negative breast cancer.

Methods

Women with HER2-positive (n = 34) and HER2-negative (n = 16) breast cancer underwent PET/CT 5 ± 2 days following [89Zr]trastuzumab administration. HER2 status was determined based on immunohistochemistry and/or fluorescence in situ hybridization of primary or metastatic/recurrent tumor. Tumor [89Zr]trastuzumab uptake was assessed qualitatively and semiquantitatively as maximum standardized uptake value (SUVmax), and correlated with HER2 status. Additionally, intrapatient heterogeneity of [89Zr]trastuzumab uptake was evaluated.

Results

On a per-patient basis, [89Zr]trastuzumab-PET/CT was positive in 30/34 (88.2%) HER2-positive and negative in 15/16 (93.7%) HER2-negative patients. Considering all lesions, the SUVmax was not significantly different in patients with HER2-positive versus HER2-negative disease (p = 0.06). The same was true of when only hepatic lesions were evaluated (p = 0.42). However, after excluding hepatic lesions, tumor SUVmax was significantly higher in HER2-positive compared to HER2-negative patients (p = 0.003). A cutoff SUVmax of 3.2, determined by ROC analysis, demonstrated positive-predictive value of 83.3% (95% CI 65.3%, 94.4%), sensitivity of 75.8% (57.7%, 88.9%), negative-predictive value of 50% (24.7%, 75.3%), and specificity of 61.5% (95% 31.6%, 86.1%) for differentiating HER2-positive from HER2-negative lesions. There was intrapatient heterogeneity of [89Zr]trastuzumab uptake in 20% of patients with multiple lesions.

Conclusions

[89Zr]trastuzumab has the potential to characterize the HER2 status of the complete tumor burden in patients with breast cancer, thus obviating repeat or multiple tissue sampling to assess intrapatient heterogeneity of HER2 status.

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Acknowledgements

This work was supported by National Cancer Institute Grant CA182945, U.S. Department of Energy Grant DE-SC0012737, and the Alvin J. Siteman Cancer Center Imaging and Response Assessment Core.

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Authors and Affiliations

  1. Siteman Cancer Center, Washington University School of Medicine, St. Louis, MO, USA

    Farrokh Dehdashti, Ningying Wu, Ron Bose, Michael J. Naughton, Cynthia X. Ma, Buck E. Rogers, Richard Laforest & Barry A. Siegel

  2. Edward Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, MO, USA

    Farrokh Dehdashti, Richard Laforest & Barry A. Siegel

  3. Division of Public Health Sciences, Department of Surgery, Washington University School of Medicine, St. Louis, MO, USA

    Ningying Wu

  4. Division of Oncology, Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA

    Ron Bose, Michael J. Naughton & Cynthia X. Ma

  5. Department of Radiology, Yale University School of Medicine, New Haven, CT, USA

    Bernadette V. Marquez-Nostra

  6. Department of Radiaton Oncology, Washington University School of Medicine, St. Louis, MO, USA

    Philipp Diebolder, Cedric Mpoy & Buck E. Rogers

  7. Departments of Radiology and Chemistry, University of Alabama at Birmingham, Birmingham, AL, USA

    Suzanne E. Lapi

  8. Mallinckrodt Institute of Radiology, Campus Box 8223, 510 South Kingshighway Blvd., St. Louis, MO, 63110, USA

    Farrokh Dehdashti

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  1. Farrokh Dehdashti
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  2. Ningying Wu
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  3. Ron Bose
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  5. Cynthia X. Ma
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  6. Bernadette V. Marquez-Nostra
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  7. Philipp Diebolder
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  9. Buck E. Rogers
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  10. Suzanne E. Lapi
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  11. Richard Laforest
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  12. Barry A. Siegel
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Correspondence to Farrokh Dehdashti.

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The authors declare that they have no conflict of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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Informed consent was obtained from all individual participants included in the study.

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Dehdashti, F., Wu, N., Bose, R. et al. Evaluation of [89Zr]trastuzumab-PET/CT in differentiating HER2-positive from HER2-negative breast cancer. Breast Cancer Res Treat 169, 523–530 (2018). https://doi.org/10.1007/s10549-018-4696-z

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  • DOI: https://doi.org/10.1007/s10549-018-4696-z

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