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Research ArticleOncology

18F-Fluoroestradiol PET Imaging in a Phase II Trial of Vorinostat to Restore Endocrine Sensitivity in ER+/HER2− Metastatic Breast Cancer

Lanell M. Peterson, Brenda F. Kurland, Fengting Yan, Alena Novakova- Jiresova, Vijayakrishna K. Gadi, Jennifer M. Specht, Julie R. Gralow, Erin K. Schubert, Jeanne M. Link, Kenneth A. Krohn, Janet F. Eary, David A. Mankoff and Hannah M. Linden
Journal of Nuclear Medicine February 2021, 62 (2) 184-190; DOI: https://doi.org/10.2967/jnumed.120.244459
Lanell M. Peterson
1Division of Medical Oncology, University of Washington/Seattle Cancer Care Alliance, Seattle, Washington
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Brenda F. Kurland
2Department of Biostatistics, University of Pittsburgh, Pittsburgh, Pennsylvania
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Fengting Yan
1Division of Medical Oncology, University of Washington/Seattle Cancer Care Alliance, Seattle, Washington
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Alena Novakova- Jiresova
3Department of Oncology, First Faculty of Medicine, Charles University and Thomayer Hospital, Prague, Czech Republic
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Vijayakrishna K. Gadi
1Division of Medical Oncology, University of Washington/Seattle Cancer Care Alliance, Seattle, Washington
4Clinical Research and Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington
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Jennifer M. Specht
1Division of Medical Oncology, University of Washington/Seattle Cancer Care Alliance, Seattle, Washington
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Julie R. Gralow
1Division of Medical Oncology, University of Washington/Seattle Cancer Care Alliance, Seattle, Washington
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Erin K. Schubert
5Department of Radiology, University of Pennsylvania, Philadelphia, Pennsylvania
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Jeanne M. Link
6Department of Diagnostic Radiology, Oregon Health and Science University, Portland, Oregon; and
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Kenneth A. Krohn
6Department of Diagnostic Radiology, Oregon Health and Science University, Portland, Oregon; and
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Janet F. Eary
7Cancer Imaging Program, National Cancer Institute, Bethesda, Maryland
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David A. Mankoff
5Department of Radiology, University of Pennsylvania, Philadelphia, Pennsylvania
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Hannah M. Linden
1Division of Medical Oncology, University of Washington/Seattle Cancer Care Alliance, Seattle, Washington
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Abstract

Histone deacetylase inhibitors (HDACIs) may overcome endocrine resistance in estrogen receptor–positive (ER+) metastatic breast cancer. We tested whether 18F-fluoroestradiol PET imaging would elucidate the pharmacodynamics of combination HDACIs and endocrine therapy. Methods: Patients with ER+/human epidermal growth factor receptor 2 (HER2)–negative metastatic breast cancer with prior clinical benefit from endocrine therapy but later progression on aromatase inhibitor (AI) therapy were given vorinostat (400 mg daily) sequentially or simultaneously with AI. 18F-fluoroestradiol PET and 18F-FDG PET scans were performed at baseline, week 2, and week 8. Results: Eight patients were treated sequentially, and then 15 simultaneously. Eight patients had stable disease at week 8, and 6 of these 8 patients had more than 6 mo of stable disease. Higher baseline 18F-fluoroestradiol uptake was associated with longer progression-free survival. 18F-fluoroestradiol uptake did not systematically increase with vorinostat exposure, indicating no change in regional ER estradiol binding, and 18F-FDG uptake did not show a significant decrease, as would have been expected with tumor regression. Conclusion: Simultaneous HDACIs and AI dosing in patients with cancer resistant to AI alone showed clinical benefit (6 or more months without progression) in 4 of 10 evaluable patients. Higher 18F-fluoroestradiol PET uptake identified patients likely to benefit from combination therapy, but vorinostat did not change ER expression at the level of detection of 18F-fluoroestradiol PET.

  • FES
  • vorinostat
  • ER+ breast cancer
  • metastatic breast cancer
  • estrogen receptors

Footnotes

  • Published online Jun. 26, 2020.

  • © 2021 by the Society of Nuclear Medicine and Molecular Imaging.
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Journal of Nuclear Medicine: 62 (2)
Journal of Nuclear Medicine
Vol. 62, Issue 2
February 1, 2021
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18F-Fluoroestradiol PET Imaging in a Phase II Trial of Vorinostat to Restore Endocrine Sensitivity in ER+/HER2− Metastatic Breast Cancer
Lanell M. Peterson, Brenda F. Kurland, Fengting Yan, Alena Novakova- Jiresova, Vijayakrishna K. Gadi, Jennifer M. Specht, Julie R. Gralow, Erin K. Schubert, Jeanne M. Link, Kenneth A. Krohn, Janet F. Eary, David A. Mankoff, Hannah M. Linden
Journal of Nuclear Medicine Feb 2021, 62 (2) 184-190; DOI: 10.2967/jnumed.120.244459

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18F-Fluoroestradiol PET Imaging in a Phase II Trial of Vorinostat to Restore Endocrine Sensitivity in ER+/HER2− Metastatic Breast Cancer
Lanell M. Peterson, Brenda F. Kurland, Fengting Yan, Alena Novakova- Jiresova, Vijayakrishna K. Gadi, Jennifer M. Specht, Julie R. Gralow, Erin K. Schubert, Jeanne M. Link, Kenneth A. Krohn, Janet F. Eary, David A. Mankoff, Hannah M. Linden
Journal of Nuclear Medicine Feb 2021, 62 (2) 184-190; DOI: 10.2967/jnumed.120.244459
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Keywords

  • FES
  • vorinostat
  • ER+ breast cancer
  • metastatic breast cancer
  • estrogen receptors
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