在患有乳腺癌和妇科癌症的患者中,ESR1变化的表征
Gargi D Basu1, Paige E Innis1, Angela K Deem1
1Exact Sciences Corporation, 5505 Endeavor Ln, Madison, WI, 53719, USA.
Breast cancer research : BCR
|January 20, 2026
概括
雌激素受体1 (ESR1) 变化在转移性乳腺癌中很常见,特别是在HR+/HER2-亚型中,并且与内分泌治疗耐药性有关. 这些变化,包括误解突变和融合,与其他可操作的生物标志物同时发生,为治疗决策提供了信息.
科学领域:
- 在瘤学瘤学.
- 基因组学就是基因组学.
- 分子生物学分子生物学
背景情况:
- 雌激素受体1 (ESR1) 变化是激素驱动癌症中对内分泌疗法 (ET) 耐药性的关键机制.
- 针对性治疗的不断变化需要对ESR1变化及其临床影响有更深入的了解.
研究的目的:
- 调查乳腺癌 (BC) 和妇科癌样本中ESR1的分布和共同变化.
- 为了比较本地/区域和转移性BC样本之间的ESR1变化频率,以及跨BC亚型.
- 在ESR1-改变的瘤中识别并发的治疗可行的生物标志物.
主要方法:
- 对2574个BC和1110个妇科癌症样本进行了回顾性分析.
- 整体外基因组和整体转录基因组分析,以评估ESR1的变化和共同变化.
- 基于瘤部位 (局部/区域与转移) 和癌症亚型的变化频率的比较.
主要成果:
- 在6.2%的BC和3.4%的妇科癌症样本中发现了ESR1的改变.
- 在HR+/HER2-BC中,ESR1变异 (整体和错误突变) 和ESR1融合在转移样本中明显更频繁.
- 在这两种癌症类型中,CCDC170是ESR1融合最常见的融合伙伴. 治疗相关的共同改变 (例如,FGF3/4/19,CCND1放大) 被丰富在ESR1改变的HR+/HER2-BC.中.
结论:
- 在转移性HR+/HER2-BC中,ESR1变异,特别是误解突变更为普遍,支持它们在ET耐药性和进展中的作用.
- 随着ESR1变化与可操作的生物标志物的同时发生,为临床决策提供了潜在的目标.
- 在妇科瘤中ESR1的改变可能具有预后和治疗相关性.
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