Towards personalized treatment for early stage HER2-positive breast cancer.
Towards personalized treatment for early stage HER2-positive breast cancer.
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针对早期 HER2 阳性乳腺癌的个性化治疗。
DOI：
10.1038/s41571-019-0299-9
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发表时间：
2020-04
期刊：
影响因子：
--
通讯作者：
Schiff R
中科院分区：
文献类型：
--
作者：
Goutsouliak K;Veeraraghavan J;Sethunath V;De Angelis C;Osborne CK;Rimawi MF;Schiff R
HER 2靶向治疗的进展改善了HER 2阳性乳腺癌患者的生存率。局部疾病的标准治疗是化疗和1年的辅助HER 2靶向治疗，通常使用抗HER 2抗体曲妥珠单抗。尽管这种治疗有效，但在一部分患者中会发生疾病复发;因此，重点放在通过联合不同的HER 2靶向药物或延长HER 2靶向治疗的持续时间来加强治疗。事实上，双重HER 2靶向疗法和持续时间延长的抗HER 2疗法，以及使用抗HER 2抗体-药物缀合物T-DM 1的辅助疗法都已被批准用于临床应用。然而，新出现的证据表明，一些患者没有从这些额外的治疗中获得足够的益处来抵消相关的毒性和/或成本。同样，化疗的普遍使用可能不会使所有患者受益，通过省略化疗的治疗降级已在临床试验中显示出希望，目前正在进一步探索。因此，精准医疗的未来应该包括根据每个肿瘤的遗传学和生物学以及每个患者的临床特征定制治疗。预测性生物标志物能够识别将从升级或降级治疗中受益的患者，这对这种方法至关重要。在这篇综述中，我们总结了现有的HER 2靶向药物和相关的耐药机制，并描述了目前早期HER 2阳性乳腺癌的治疗前景，重点是治疗升级或降级的策略。HER 2靶向治疗极大地改善了HER 2阳性乳腺癌患者的预后，目前已有一系列药物获得批准或处于后期临床开发阶段。在精准医学时代，人们正在努力通过个性化HER 2靶向治疗方案来进一步改善患者的治疗效果，主要是根据疾病生物学进行治疗的升级或降级。在这篇综述中，作者概述了HER 2靶向治疗的现状，并讨论了支持这种定制治疗策略的证据。
Advances in HER2-targeted therapies have improved the survival of patients with HER2-positive breast cancer. The standard-of-care treatment for localized disease has been chemotherapy and 1 year of adjuvant HER2-targeted therapy, typically with the anti-HER2 antibody trastuzumab. Despite the effectiveness of this treatment, disease relapse occurs in a subset of patients; thus, focus has been placed on escalating treatment by either combining different HER2-targeted agents or extending the duration of HER2-targeted therapy. Indeed, dual HER2-targeted therapies and extended-duration anti-HER2 therapy, as well as adjuvant therapy with the anti-HER2 antibody–drug conjugant T-DM1, have all been approved for clinical use. Emerging evidence suggests, however, that some patients do not derive sufficient benefit from these additional therapies to offset the associated toxicities and/or costs. Similarly, the universal use of chemotherapy might not benefit all patients, and treatment de-escalation through omission of chemotherapy has shown promise in clinical trials and is currently being explored further. The future of precision medicine should therefore involve tailoring of therapy based on the genetics and biology of each tumour and the clinical characteristics of each patient. Predictive biomarkers that enable the identification of patients who will benefit from either escalated or de-escalated treatment will be crucial to this approach. In this Review, we summarize the available HER2-targeted agents and associated mechanisms of resistance, and describe the current therapeutic landscape of early stage HER2-positive breast cancer, focusing on strategies for treatment escalation or de-escalation. HER2-targeted therapy has greatly improved the outcomes of patients with HER2-positive breast cancer, with a range of agents now approved or in late-stage clinical development. In the era of precision medicine, efforts are being made to further improve patient outcomes by personalizing HER2-targeted treatment regimens, primarily though escalation or de-escalation of therapy according to the disease biology. In this Review, the authors provide an overview of the current landscape of HER2-targeted therapy and discuss the evidence supporting such tailored therapeutic strategies.
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双脂肪酸合酶和HER2信号阻滞显示出针对抗抗HEH2药物的乳腺癌模型的明显抗肿瘤活性。
影响因子：
3.7
作者：
Blancafort A;Giró-Perafita A;Oliveras G;Palomeras S;Turrado C;Campuzano Ò;Carrión-Salip D;Massaguer A;Brugada R;Palafox M;Gómez-Miragaya J;González-Suárez E;Puig T
通讯作者：
Puig T
影响因子：
50.5
作者：
Bianchini, G.;Pusztai, L.;Gianni, L.
通讯作者：
Gianni, L.
影响因子：
6.6
作者：
Boulbes DR;Arold ST;Chauhan GB;Blachno KV;Deng N;Chang WC;Jin Q;Huang TH;Hsu JM;Brady SW;Bartholomeusz C;Ladbury JE;Stone S;Yu D;Hung MC;Esteva FJ
通讯作者：
Esteva FJ
DOI：
10.1016/s1470-2045(17)30777-5
发表时间：
2018-01
期刊：
The Lancet. Oncology
影响因子：
--
作者：
Early Breast Cancer Trialists' Collaborative Group (EBCTCG)
通讯作者：
Early Breast Cancer Trialists' Collaborative Group (EBCTCG)
影响因子：
45.3
作者：
Carey, Lisa A.;Berry, Donald A.;Hudis, Clifford A.
通讯作者：
Hudis, Clifford A.