Somatic Activating ESR1 Mutation in an Aggressive Prolactinoma.

Autor:	Paes T; Division of Endocrinology, Diabetes and Hypertension, Brigham and Women's Hospital and Harvard Medical School, Boston, MA., Buelvas Mebarak J; Division of Endocrinology, Diabetes and Hypertension, Brigham and Women's Hospital and Harvard Medical School, Boston, MA., Magnotto JC; Division of Endocrinology, Diabetes and Hypertension, Brigham and Women's Hospital and Harvard Medical School, Boston, MA., Stamatiades GA; Division of Endocrinology, Diabetes and Hypertension, Brigham and Women's Hospital and Harvard Medical School, Boston, MA., Kuang Y; Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA., Paweletz C; Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA., Laws ER; Department of Neurosurgery, Brigham and Women's Hospital and Harvard Medical School, Boston, MA., Grosek N; Division of Endocrinology, Diabetes and Hypertension, Brigham and Women's Hospital and Harvard Medical School, Boston, MA., Carroll RS; Division of Endocrinology, Diabetes and Hypertension, Brigham and Women's Hospital and Harvard Medical School, Boston, MA., Jeselsohn R; Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA., Mohan DR; Department of Medicine, Washington University School of Medicine, St. Louis, MO., Lerario AM; Department of Internal Medicine, Division of Metabolism, Endocrinology, and Diabetes, University of Michigan, Ann Arbor, MI., Truong MT; Department of Radiation Oncology, Boston University Medical Center, Boston, MA., Bi WL; Department of Neurosurgery, Brigham and Women's Hospital and Harvard Medical School, Boston, MA., Reardon DA; Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA., Meredith DM; Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA., Kaiser UB; Division of Endocrinology, Diabetes and Hypertension, Brigham and Women's Hospital and Harvard Medical School, Boston, MA., Abreu AP; Division of Endocrinology, Diabetes and Hypertension, Brigham and Women's Hospital and Harvard Medical School, Boston, MA.
Jazyk:	angličtina
Zdroj:	The Journal of clinical endocrinology and metabolism [J Clin Endocrinol Metab] 2024 Sep 06. Date of Electronic Publication: 2024 Sep 06.
DOI:	10.1210/clinem/dgae615
Abstrakt:	Context and Objective: The genetic profile of prolactinomas remains poorly understood. Our objective is to identify somatic genetic alterations associated with prolactinomas and to report the identification of an activating ESR1 mutation (ESR1Y537S) in an aggressive prolactinoma. Setting: Brigham and Women's Hospital. Design: Massively parallel-sequencing panel (OncoPanel) was performed in a cohort of patients with prolactinomas to identify mutations and copy number variation (CNV). Results: Twenty subjects (mean age 38.6 years; 12 women and 8 men) were included in this study. A somatic ESR1Y537S mutation was identified in an aggressive prolactinoma in a post-menopausal woman. No SF3B1 or other somatic mutations were identified. The median number of CNV events identified in our samples was 46; the prolactinoma with ESR1Y537S had the highest number with 233 events. In breast cancer, ESR1Y537S has been shown to activate estrogen receptor alpha independent of ligand binding. In patients with resistant breast cancer and ESR1Y537S, elacestrant, a second-line ER degrader, improves progression-free survival. Therefore, given the lack of response to multimodality therapies, elacestrant was initiated in this patient after the third cycle of radiotherapy. Elacestrant, along with radiotherapy, controlled tumor growth and significantly reduced prolactin levels. Conclusion: Molecular profiling allowed the identification of ESR1Y537S, in an aggressive prolactinoma. ESR1Y537S was not detected early in the course of the disease and is likely conferring tumor aggressiveness. This finding emphasizes the significance of estrogen receptor signaling in prolactinomas. It also allowed the use of targeted therapy with successful control of disease progression. (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com. See the journal About page for additional terms.)
Databáze:	MEDLINE
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