Lanell M Peterson1, Brenda F Kurland2, Fengting Yan1, Alena Novakova- Jiresova3, Vijayakrishna K Gadi1,4, Jennifer M Specht1, Julie R Gralow1, Erin K Schubert5, Jeanne M Link6, Kenneth A Krohn6, Janet F Eary7, David A Mankoff5, Hannah M Linden8. 1. Division of Medical Oncology, University of Washington/Seattle Cancer Care Alliance, Seattle, Washington. 2. Department of Biostatistics, University of Pittsburgh, Pittsburgh, Pennsylvania. 3. Department of Oncology, First Faculty of Medicine, Charles University and Thomayer Hospital, Prague, Czech Republic. 4. Clinical Research and Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington. 5. Department of Radiology, University of Pennsylvania, Philadelphia, Pennsylvania. 6. Department of Diagnostic Radiology, Oregon Health and Science University, Portland, Oregon; and. 7. Cancer Imaging Program, National Cancer Institute, Bethesda, Maryland. 8. Division of Medical Oncology, University of Washington/Seattle Cancer Care Alliance, Seattle, Washington hmlinden@uw.edu.
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.
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: Scott Thomas; Kenneth T Thurn; Elona Biçaku; Douglas C Marchion; Pamela N Münster Journal: Breast Cancer Res Treat Date: 2011-02-05 Impact factor: 4.872
Authors: Roisin M Connolly; Jeffrey P Leal; Matthew P Goetz; Zhe Zhang; Xian C Zhou; Lisa K Jacobs; Joyce Mhlanga; Joo H O; John Carpenter; Anna Maria Storniolo; Stanley Watkins; John H Fetting; Robert S Miller; Kostandinos Sideras; Stacie C Jeter; Bridget Walsh; Penny Powers; Jane Zorzi; Judy C Boughey; Nancy E Davidson; Lisa A Carey; Antonio C Wolff; Nagi Khouri; Edward Gabrielson; Richard L Wahl; Vered Stearns Journal: J Nucl Med Date: 2014-12-04 Impact factor: 10.057
Authors: Lanell M Peterson; David A Mankoff; Thomas Lawton; Kevin Yagle; Erin K Schubert; Svetlana Stekhova; Allen Gown; Jeanne M Link; Timothy Tewson; Kenneth A Krohn Journal: J Nucl Med Date: 2008-02-20 Impact factor: 10.057
Authors: Brenda F Kurland; Lanell M Peterson; Andrew T Shields; Jean H Lee; Darrin W Byrd; Alena Novakova-Jiresova; Mark Muzi; Jennifer M Specht; David A Mankoff; Hannah M Linden; Paul E Kinahan Journal: J Nucl Med Date: 2018-10-25 Impact factor: 10.057
Authors: Brenda F Kurland; Vijayakrishna K Gadi; Jennifer M Specht; Kimberly H Allison; Robert B Livingston; Eve T Rodler; Lanell M Peterson; Erin K Schubert; Xiaoyu Chai; David A Mankoff; Hannah M Linden Journal: EJNMMI Res Date: 2012-06-25 Impact factor: 3.138
Authors: R G Koleva-Kolarova; M J W Greuter; M van Kruchten; K M Vermeulen; T Feenstra; E Buskens; A W J M Glaudemans; E F J de Vries; E G E de Vries; G A P Hospers; G H de Bock Journal: Br J Cancer Date: 2015-04-16 Impact factor: 7.640