University of North Carolina, 170 Manning Drive, Chapel Hill, NC 27599-7305, USA.
Nat Rev Clin Oncol. 2010 Dec;7(12):683-92. doi: 10.1038/nrclinonc.2010.154. Epub 2010 Sep 28.
This Review outlines the understanding and management of triple-negative breast cancer (TNBC). TNBC shares morphological and genetic abnormalities with basal-like breast cancer (BLBC), a subgroup of breast cancer defined by gene-expression profiling. However, TNBC and BLBC tumors are heterogeneous and overlap is incomplete. Breast cancers found in BRCA1 mutation carriers are also frequently triple negative and basal like. TNBC and BLBC occur most frequently in young women, especially African Americans, and tend to exhibit aggressive, metastatic behavior. These tumors respond to conventional chemotherapy but relapse more frequently than hormone receptor-positive, luminal subtypes and have a worse prognosis. New systemic therapies are urgently needed as most patients with TNBC and/or BLBC relapse with distant metastases, and hormonal therapies and HER2-targeted agents are ineffective in this group of tumors. Poly (ADP-ribose) polymerase inhibitors, angiogenesis inhibitors, EGFR-targeted agents, and src kinase and mTOR inhibitors are among the therapeutic agents being actively investigated in clinical trials in patients with TNBC and/or BRCA1-associated tumors. Increased understanding of the genetic abnormalities involved in the pathogenesis of TNBC, BLBC and BRCA1-associated tumors is opening up new therapeutic possibilities for these hard-to-treat breast cancers.
这篇综述概述了三阴性乳腺癌(TNBC)的认识和治疗。TNBC 与基底样乳腺癌(BLBC)具有形态和遗传异常,BLBC 是通过基因表达谱定义的乳腺癌亚组。然而,TNBC 和 BLBC 肿瘤具有异质性,并且重叠不完全。BRCA1 突变携带者中的乳腺癌也经常是三阴性和基底样的。TNBC 和 BLBC 最常发生在年轻女性中,尤其是非裔美国人,并且往往表现出侵袭性、转移性行为。这些肿瘤对常规化疗有反应,但比激素受体阳性、腔型亚型更容易复发,并且预后更差。由于大多数 TNBC 和/或 BLBC 患者伴有远处转移而复发,激素治疗和 HER2 靶向药物在这组肿瘤中无效,因此迫切需要新的系统治疗方法。聚(ADP-核糖)聚合酶抑制剂、血管生成抑制剂、EGFR 靶向药物、src 激酶和 mTOR 抑制剂是正在临床试验中积极研究用于治疗 TNBC 和/或 BRCA1 相关肿瘤的治疗药物之一。对参与 TNBC、BLBC 和 BRCA1 相关肿瘤发病机制的遗传异常的深入了解为这些难以治疗的乳腺癌开辟了新的治疗可能性。