Clinical implications of the intrinsic molecular subtypes of breast cancer
Clinical implications of the intrinsic molecular subtypes of breast cancer
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DOI：
10.1016/j.breast.2015.07.008
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发表时间：
2015-11-01
期刊：
影响因子：
3.9
通讯作者：
Munoz, Montserrat
中科院分区：
文献类型：
--
作者：
Prat, Aleix;Pineda, Estela;Munoz, Montserrat
基因表达谱分析对我们理解乳腺癌生物学产生了相当大的影响。在过去的15年中，已经鉴定并深入研究了乳腺癌的5种内在分子亚型（管腔A、管腔B、HER 2富集、基底样和Claudin低）。在这篇综述中，我们将重点关注2013年圣加仑共识建议认可的当前基于病理的分类之外的内在分子亚型的当前和未来临床意义。在激素受体阳性和HER 2阴性的早期乳腺癌中，管腔A和B亚型可预测10年的结局，无论是否给予全身治疗以及5年内分泌治疗后远处复发的剩余风险。在临床HER 2阳性疾病中，可以鉴定出4种主要的内在亚型，并主导生物学和临床表型。从临床角度来看，HER 2_/HER 2富集疾病患者似乎从新辅助曲妥珠单抗或曲妥珠单抗/拉帕替尼双重HER 2阻断联合化疗中获益最大，与其他亚型相比，HER 2_/Luminal A疾病患者似乎具有相对更好的结局。最后，在三阴性乳腺癌（TNBC）中，基底样疾病占主导地位（70-80%），从生物学角度来看，应将其本身视为癌症类型。重要的是，TNBC中基底细胞样与非基底细胞样之间的差异可能预测（新）辅助多药化疗后的生存期，贝伐珠单抗在新辅助治疗中的获益（CALGB 40603），以及多西他赛与卡铂相比在一线转移性疾病中的获益（TNT研究）。总的来说，这些数据表明，内在分子谱提供了超出当前基于病理学的分类的临床相关信息。(C)2015作者爱思唯尔有限公司出版
Gene-expression profiling has had a considerable impact on our understanding of breast cancer biology. During the last 15 years, 5 intrinsic molecular subtypes of breast cancer (Luminal A, Luminal B, HER2-enriched, Basal-like and Claudin-low) have been identified and intensively studied. In this review, we will focus on the current and future clinical implications of the intrinsic molecular subtypes beyond the current pathological-based classification endorsed by the 2013 St. Gallen Consensus Recommendations. Within hormone receptor-positive and HER2-negative early breast cancer, the Luminal A and B subtypes predict 10-year outcome regardless of systemic treatment administered as well as residual risk of distant recurrence after 5 years of endocrine therapy. Within clinically HER2-positive disease, the 4 main intrinsic subtypes can be identified and dominate the biological and clinical phenotype. From a clinical perspective, patients with HER2_/HER2-enriched disease seem to benefit the most from neoadjuvant trastuzumab, or dual HER2 blockade with trastuzumab/lapatinib, in combination with chemotherapy, and patients with HER2_/Luminal A disease seem to have a relative better outcome compared to the other subtypes. Finally, within triple-negative breast cancer (TNBC), the Basal-like disease predominates (70-80%) and, from a biological perspective, should be considered a cancer-type by itself. Importantly, the distinction between Basal-like versus non-Basal-like within TNBC might predict survival following (neo) adjvuvant multi-agent chemotherapy, bevacizumab benefit in the neoadjuvant setting (CALGB40603), and docetaxel vs. carboplatin benefit in first-line metastatic disease (TNT study). Overall, this data suggests that intrinsic molecular profiling provides clinically relevant information beyond current pathology-based classifications. (C) 2015 The Authors. Published by Elsevier Ltd.