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

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.

• Authors: 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: Journal of nuclear medicine : official publication, Society of Nuclear Medicine (J Nucl Med) Vol. 62 Issue 2 Pg. 184-190 (02 2021) ISSN: 1535-5667 [Electronic] United States
• PMID: 32591490 (Publication Type: Clinical Trial, Phase II, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: © 2021 by the Society of Nuclear Medicine and Molecular Imaging.

Chemical References

• Receptors, Estrogen
• Estradiol
• Vorinostat
• 16-fluoroestradiol
• ERBB2 protein, human
• Receptor, ErbB-2

Topics

• Adult
• Aged
• Breast Neoplasms (diagnostic imaging, metabolism, pathology)
• Estradiol (analogs & derivatives)
• Female
• Humans
• Image Processing, Computer-Assisted
• Middle Aged
• Neoplasm Metastasis
• Positron-Emission Tomography
• Receptor, ErbB-2 (metabolism)
• Receptors, Estrogen (metabolism)
• Vorinostat (pharmacology)