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早期三阴性乳腺癌治疗进展。

Update on the Treatment of Early-Stage Triple-Negative Breast Cancer.

机构信息

Division of Medical Oncology, University of Kansas Medical Center, 2330 Shawnee Mission Pkwy, Westwood, KS, 66205, USA.

出版信息

Curr Treat Options Oncol. 2018 Apr 14;19(5):22. doi: 10.1007/s11864-018-0539-8.

DOI:10.1007/s11864-018-0539-8
PMID:29656345
Abstract

Triple-negative breast cancer (TNBC) accounts for 15% of all breast cancers and is associated with poor long-term outcomes compared to other breast cancer subtypes. Currently, chemotherapy remains the main modality of treatment for early-stage TNBC, as there is no approved targeted therapy for this subtype. The biologic heterogeneity of TNBC has hindered the development and evaluation of novel agents, but recent advancements in subclassifying TNBC have paved the way for further investigation of more effective systemic therapies, including cytotoxic and targeted agents. TNBC is enriched for germline BRCA mutation and for somatic deficiencies in homologous recombination DNA repair, the so-called "BRCAness" phenotype. Together, germline BRCA mutations and BRCAness are promising biomarkers of susceptibility to DNA-damaging therapy. Various investigational approaches are consequently being investigated in early-stage TNBC, including immune checkpoint inhibitors, platinum compounds, PI3K pathway inhibitors, and androgen receptor inhibitors. Due to the biological diversity found within TNBC, patient selection based on molecular biomarkers could aid the design of early-phase clinical trials, ultimately accelerating the clinical application of effective new agents. TNBC is an aggressive breast cancer subtype, for which multiple targeted approaches will likely be required for patient outcomes to be substantially improved.

摘要

三阴性乳腺癌(TNBC)占所有乳腺癌的 15%,与其他乳腺癌亚型相比,其长期预后较差。目前,化疗仍然是早期 TNBC 的主要治疗方式,因为针对这种亚型尚未批准靶向治疗。TNBC 的生物学异质性阻碍了新型药物的开发和评估,但最近对 TNBC 的细分分类为进一步研究更有效的全身治疗方法铺平了道路,包括细胞毒性和靶向药物。TNBC 中富含种系 BRCA 突变和同源重组 DNA 修复的体细胞缺陷,即所谓的“BRCAness”表型。种系 BRCA 突变和 BRCAness 共同成为对 DNA 损伤治疗敏感的有前途的生物标志物。因此,各种研究方法正在早期 TNBC 中进行研究,包括免疫检查点抑制剂、铂类化合物、PI3K 通路抑制剂和雄激素受体抑制剂。由于 TNBC 中存在生物学多样性,基于分子生物标志物的患者选择可能有助于设计早期临床试验,最终加速有效新药物的临床应用。TNBC 是一种侵袭性乳腺癌亚型,为了显著改善患者的预后,可能需要多种靶向方法。

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Ann Oncol. 2018 Mar 1;29(3):654-660. doi: 10.1093/annonc/mdx821.
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Olaparib for Metastatic Breast Cancer in Patients with a Germline BRCA Mutation.奥拉帕利治疗携种系 BRCA 突变的转移性乳腺癌患者。
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Adjuvant Capecitabine for Breast Cancer after Preoperative Chemotherapy.
三阴性乳腺癌化疗时机的影响:一项真实世界证据研究。
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Evaluating Treatment Outcomes in Women with Node-Negative T1 Breast Cancers.评估淋巴结阴性T1期乳腺癌女性患者的治疗结果
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NAT10/ac4C/JunB facilitates TNBC malignant progression and immunosuppression by driving glycolysis addiction.NAT10/ac4C/JunB 通过驱动糖酵解成瘾促进三阴性乳腺癌的恶性进展和免疫抑制。
J Exp Clin Cancer Res. 2024 Oct 4;43(1):278. doi: 10.1186/s13046-024-03200-x.
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J Pers Med. 2024 Sep 5;14(9):944. doi: 10.3390/jpm14090944.
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