在新辅助化疗后残留疾病的HR+/HER2-BC患者中PI3K/PTEN/mTOR通路的动态跟踪和预后价值:一项队列研究
Federica Miglietta1,2, Valentina Carraro3, Ottavia Amato4,2
1Department of Surgery, Oncology and Gastroenterology (DISCOG), University of Padua, Padova, Italy federica.miglietta@unipd.it.
Journal of clinical pathology
|June 21, 2023
概括
激素受体阳性乳腺癌中的PI3K/PTEN/mTOR通路在新辅助化疗期间是动态的. 了解超出PIK3CA突变的途径改变对于预测治疗反应至关重要.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 遗传学 遗传学 是一个
背景情况:
- 激素受体阳性 (HR+) / HER2-乳腺癌 (BC) 是分子多样性的.
- PI3K/PTEN/mTOR路径与BC异质性有关.
- 在新辅助化疗 (NACT) 期间需要对这种途径进行纵向分析.
研究的目的:
- 追踪从基线到残留疾病 (RD) 和转移的PI3K/PTEN/mTOR途径动态在接受NACT的HR+/HER2-BC患者中.
- 为了将路径变化与无复发生存率 (RFS) 相关联.
主要方法:
- 评估了92名HR+/HER2-BC患者的基线和RD样本中的PIK3CA突变,Pten损失和mTOR/基质酸化.
- 在复发时分析PIK3CA状态的转移样本.
- 使用RFS作为主要终点.
主要成果:
- 在12.8%的患者中发生了PIK3CA突变状态转换.
- 在33.3%的患者中观察到Pten损失转化.
- mTOR酸化增加,而其基质从基线减少到RD;基线p-mTOR在PIK3CA野生类型病例中预测了较差的RFS,而p-p70S6K与RFS积极相关.
结论:
- 在NACT下,PI3K/PTEN/mTOR路径表现出显著的活力.
- 单独的PIK3CA突变不能完全捕捉路径的复杂性.
- 替代的mTOR激活途径可能会在HR+/HER2-BC与RD中驱动化疗抵抗和内分泌抵抗,需要进一步调查.
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