期刊
CURRENT ONCOLOGY REPORTS
卷 19, 期 5, 页码 -出版社
SPRINGER
DOI: 10.1007/s11912-017-0591-8
关键词
Estrogen receptor; ESR1 mutations; Endocrine resistance; Circulating tumor DNA
类别
资金
- NCI [K08 CA191058-02]
- Breast Cancer Alliance Exceptional Award
- Breast Cancer Research Foundation
- NIH Breast Cancer Specialized Programs of Research Excellence [P50CA058183, P50CA186784]
- NIH Cancer Center [P30CA125123]
- Susan G. Komen for the Cure Foundation Promise Grants [PG12221410]
- Conquer Cancer Foundation
Recurrent ligand-binding domain ESR1 mutations have recently been detected in a substantial number of patients with metastatic ER+ breast cancer and evolve under the selective pressure of endocrine treatments. In this review, we evaluate the current understanding of the biological and clinical significance of these mutations. The preclinical studies revealed that these mutations lead to constitutive ligand-independent activity, indicating resistance to aromatase inhibitors and decreased sensitivity to tamoxifen and fulvestrant. Retrospective analyses of ESR1 mutations in baseline plasma circulating tumor DNA from completed clinical trials suggest that these mutations are prognostic and predictive of resistance to aromatase inhibitors in metastatic disease. Currently, we are lacking prospective studies to confirm these results and to determine the optimal treatment combinations for patients with the ESR1 mutations. In addition, the clinical development of novel agents to overcome resistance engendered by these mutations is also needed.
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