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三阴性乳腺癌:分子特征、发病机制、治疗和当前研究方向。

Triple-negative breast cancer: molecular features, pathogenesis, treatment and current lines of research.

机构信息

Fundación Investigación del Hospital Clínico Universitario, Av. Blasco Ibáñez 17, 46010 Valencia, Spain.

出版信息

Cancer Treat Rev. 2010 May;36(3):206-15. doi: 10.1016/j.ctrv.2009.12.002. Epub 2010 Jan 8.

Abstract

Breast cancer is a heterogeneous disease with different morphologies, molecular profiles, clinical behaviour and response to therapy. The triple negative is a particular type of breast cancer defined by absence of oestrogen and progesterone receptor expression as well as absence of ERBB2 amplification. It is characterized by its biological aggressiveness, worse prognosis and lack of a therapeutic target in contrast with hormonal receptor positive and ERBB2+ breast cancers. Given these characteristics, triple-negative breast cancer is a challenge in today's clinical practice. A new breast cancer classification emerged recently in the scientific scene based in gene expression profiles. The new subgroups (luminal, ERBB2, normal breast and basal-like) have distinct gene expression patterns and phenotypical characteristics. Triple-negative breast cancer shares phenotypical features with basal-like breast cancer, which is in turn the most aggressive and with worse outcome. Since microarray gene-expression assays are only used in the research setting, clinicians use the triple-negative definition as a surrogate of basal-like breast cancer. The aim of this review, that focuses on triple-negative breast cancer, is to summarize the most relevant knowledge on this particular type of cancer in terms of molecular features, pathogenesis, clinical characteristics, current treatments and the new therapeutic options that include the use of platinum compounds, EGFR antagonists, antiangiogenics and PARP inhibitors. Advances in research are promising and new types of active drugs will become a reality in the near future, making possible a better outcome for this subgroup of breast cancer patients.

摘要

乳腺癌是一种具有不同形态、分子谱、临床行为和对治疗反应的异质性疾病。三阴性乳腺癌是一种特殊类型的乳腺癌,其特征为雌激素和孕激素受体表达缺失以及 ERBB2 扩增缺失。与激素受体阳性和 ERBB2+乳腺癌相比,它具有更强的生物学侵袭性、更差的预后和缺乏治疗靶点。鉴于这些特征,三阴性乳腺癌是当今临床实践中的一个挑战。最近在基于基因表达谱的科学领域出现了一种新的乳腺癌分类。新的亚组( luminal、ERBB2、正常乳腺和基底样)具有不同的基因表达模式和表型特征。三阴性乳腺癌与基底样乳腺癌具有相似的表型特征,而基底样乳腺癌则是最具侵袭性和最差预后的。由于微阵列基因表达检测仅用于研究环境,临床医生将三阴性定义作为基底样乳腺癌的替代物。本综述的重点是三阴性乳腺癌,旨在总结关于这种特殊类型癌症的分子特征、发病机制、临床特征、当前治疗方法以及新的治疗选择(包括使用铂化合物、EGFR 拮抗剂、抗血管生成药物和 PARP 抑制剂)的最相关知识。研究的进展是有希望的,新型活性药物将在不久的将来成为现实,使这组乳腺癌患者的预后得到改善。

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