Paes Ticiana, Buelvas Mebarak Jacobo, Magnotto John C, Stamatiades George A, Kuang Yanan, Paweletz Cloud P, Laws Edward R, Grosek Natalie, Carroll Rona S, Jeselsohn Rinath, Mohan Dipika R, Marcondes Lerario Antonio, Truong Minh T, Bi Wenya Linda, Reardon David A, Meredith David M, Kaiser Ursula B, Abreu Ana Paula
Division of Endocrinology, Diabetes and Hypertension, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA 02215, USA.
J Clin Endocrinol Metab. 2025 Mar 17;110(4):1166-1176. doi: 10.1210/clinem/dgae615.
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.
Brigham and Women's Hospital.
Massively parallel-sequencing panel (OncoPanel) was performed in a cohort of patients with prolactinomas to identify mutations and copy number variation.
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 postmenopausal woman. No SF3B1 or other somatic mutations were identified. The median number of copy number variation 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 estrogen receptor 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.
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.
催乳素瘤的基因特征仍了解甚少。我们的目的是识别与催乳素瘤相关的体细胞基因改变，并报告在一例侵袭性催乳素瘤中发现的激活型ESR1突变（ESR1Y537S）。
布莱根妇女医院。
对一组催乳素瘤患者进行大规模平行测序分析（肿瘤基因检测板），以识别突变和拷贝数变异。
本研究纳入了20名受试者（平均年龄38.6岁；12名女性和8名男性）。在一名绝经后女性的侵袭性催乳素瘤中发现了体细胞ESR1Y537S突变。未发现SF3B1或其他体细胞突变。我们样本中识别出的拷贝数变异事件的中位数为46；携带ESR1Y537S的催乳素瘤事件数最多，为233起。在乳腺癌中，ESR1Y537S已被证明可独立于配体结合激活雌激素受体α。在患有耐药性乳腺癌且携带ESR1Y537S的患者中，二线雌激素受体降解剂艾拉司群可改善无进展生存期。因此，鉴于对多模式治疗无反应，该患者在放疗第三个周期后开始使用艾拉司群。艾拉司群与放疗一起控制了肿瘤生长，并显著降低了催乳素水平。
分子分析在一例侵袭性催乳素瘤中识别出了ESR1Y537S。在疾病进程早期未检测到ESR1Y537S，它可能赋予肿瘤侵袭性。这一发现强调了雌激素受体信号在催乳素瘤中的重要性。它还使得靶向治疗得以应用并成功控制了疾病进展。
