ESR1 mutations and therapeutic resistance in metastatic breast cancer: progress and remaining challenges

被引:97
作者
Herzog, Sarah K. [1 ,2 ]
Fuqua, Suzanne A. W. [1 ,2 ,3 ,4 ]
机构
[1] Baylor Coll Med, Lester & Sue Smith Breast Ctr, Houston, TX 77030 USA
[2] Baylor Coll Med, Program Integrat Mol & Biomed Sci, Houston, TX 77030 USA
[3] Baylor Coll Med, Dept Mol & Cellular Biol, Houston, TX 77030 USA
[4] Baylor Coll Med, Dan L Duncan Canc Ctr, Houston, TX 77030 USA
关键词
RECEPTOR-ALPHA MUTATIONS; TUMOR DNA ANALYSIS; DOUBLE-BLIND; POSTMENOPAUSAL WOMEN; AROMATASE INHIBITORS; AI THERAPY; FULVESTRANT; EXEMESTANE; MULTICENTER; PALBOCICLIB;
D O I
10.1038/s41416-021-01564-x
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Breast cancer accounts for 25% of the cancers in women worldwide. The most common subtype of breast cancer diagnosed is hormone receptor positive, which expresses the oestrogen receptor (ER). Targeting of the ER with endocrine therapy (ET) is the current standard of care for ER-positive (ER+) breast cancer, reducing the mortality by up to 40%. Resistance to ET, however, remains a major issue for ER + breast cancer, leading to recurrence and metastasis. One major driver of ET resistance is mutations in the ER gene (ESR1) leading to constitutive transcriptional activity and reduced ET sensitivity. These mutations are particularly detrimental in metastatic breast cancer (MBC) as they are present in as high as 36% of the patients. This review summarises the pre-clinical characterisation of ESR1 mutations and their association with clinical outcomes in MBC and primary disease. The clinically approved and investigational therapeutic options for ESR1 mutant breast cancer and the current clinical trials evaluating ESR1 mutations and ET resistance are also discussed. Finally, this review addresses pre-clinical models and multi-'omics' approaches for developing the next generation of therapeutics for ESR1 mutant and ET-resistant breast cancer.
引用
收藏
页码:174 / 186
页数:13
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