三阴性乳腺癌脑转移治疗的研究进展

曹晓珊; 杨蓓蓓; 丛斌斌; 刘红

doi:10.19401/j.cnki.1007-3639.2024.08.007

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三阴性乳腺癌脑转移治疗的研究进展

综述 | 更新时间：2025-12-31

- 三阴性乳腺癌脑转移治疗的研究进展
- The progress of treatment for brain metastases of triple-negative breast cancer
- 中国癌症杂志 2024年34卷第8期页码：777-784
- 作者机构：
  
  1. 天津医科大学肿瘤医院，国家恶性肿瘤临床医学研究中心，天津市恶性肿瘤临床医学研究中心，乳腺癌防治教育部重点实验室，天津市“肿瘤防治”重点实验室，天津 300181
  2. 山东省肿瘤防治研究院（山东省肿瘤医院），山东第一医科大学（山东省医学科学院），乳腺病中心，山东济南 250117
- 作者简介：
  
  [ "曹晓珊（ORCID: 0000-0003-3959-6780），主治医师。" ]
  刘红（ORCID: 0000-0002-3985-9504），主任医师，博士研究生导师，天津医科大学附属肿瘤医院乳腺肿瘤二病区科主任。
- 基金信息：
- DOI：10.19401/j.cnki.1007-3639.2024.08.007
  中图分类号： R737.9
- 收稿：2024-02-19，
  
  修回：2024-08-19，
  
  纸质出版：2024-08-30
- 稿件说明：
移动端阅览
曹晓珊, 杨蓓蓓, 丛斌斌, 等. 三阴性乳腺癌脑转移治疗的研究进展[J]. 中国癌症杂志, 2024,34(8):777-784.

Xiaoshan CAO, Beibei YANG, Binbin CONG, et al. The progress of treatment for brain metastases of triple-negative breast cancer[J]. China Oncology, 2024, 34(8): 777-784.
曹晓珊, 杨蓓蓓, 丛斌斌, 等. 三阴性乳腺癌脑转移治疗的研究进展[J]. 中国癌症杂志, 2024,34(8):777-784. DOI： 10.19401/j.cnki.1007-3639.2024.08.007.

Xiaoshan CAO, Beibei YANG, Binbin CONG, et al. The progress of treatment for brain metastases of triple-negative breast cancer[J]. China Oncology, 2024, 34(8): 777-784. DOI： 10.19401/j.cnki.1007-3639.2024.08.007.

摘要

乳腺癌较易发生脑转移，其发生率在恶性肿瘤中仅次于肺癌。三阴性乳腺癌（triple-negative breast cancer，TNBC）脑转移发生时间早、发生率高，且患者预后差。TNBC脑转移治疗的难点在于缺少靶向药物以及药物较难透过血脑屏障，以致全身治疗效果欠佳。目前包括手术和放疗在内的局部治疗仍是脑转移瘤的主要治疗手段，手术治疗能快速缓解脑转移患者的神经系统压迫症状，此外，手术联合放疗较单纯手术治疗或单纯放疗可改善脑转移患者预后。在放疗方面，全脑放疗（whole-brain radiation therapy，WBRT）是颅内多发转移、脑膜转移的标准治疗，WBRT可改善多发脑转移患者的生存情况，但会影响患者认知功能，要注意海马回的保护，因此对于有限数目脑转移的患者，脑部立体定向放疗已经取代全脑放疗。然而局部治疗难以有效地控制脑转移的进展且并发症较多，需辅以全身治疗等支持治疗。卡培他滨、顺铂等化疗药物可透过血脑屏障但其疗效有限，因此新型靶向药物的研发及新靶点的探索是TNBC脑转移研究的方向。近年来研究发现，携带

BRCA

基因突变的患者有更高的脑转移风险，脑转移患者

BRCA

突变比例亦较高。目前多腺苷二磷酸核糖聚合酶[poly(ADP-ribose)polymerase，PARP

]

抑制剂可用于晚期胚系

BRCA

1/2突变的TNBC患者，且可突破血脑屏障。Ⅲ期EMBRACA临床研究显示，PARP抑制剂talazoparib可使

BRCA

1/2突变的脑转移亚组获益。此外，抗体-药物偶联物（antibody-drug conjugate，ADC）德曲妥珠单抗也可透过血脑屏障，DEBBRAH等临床研究显示，德曲妥珠单抗在HER2阳性乳腺癌脑转移患者中疗效显著，在HER2低表达患者中研究目前还未达到终点，其在TNBC脑转移治疗中的效果令人期待。戈沙妥珠单抗为靶向TROP-2的新型ADC药物，Ⅲ期ASCENT临床研究显示在总体人群（包括脑转移患者）中戈沙妥珠单抗组与化疗组相比可显著延长晚期TNBC患者无进展生存期。肽-紫杉醇共轭物ANG1005已经在Ⅱ期临床研究中显示其对TNBC脑转移患者有疗效。另外，磷脂酰肌醇3-激酶（phosphoinositide3-kinase，PI3K）/蛋白激酶B（protein kinase，AKT）/哺乳动物雷帕霉素靶蛋白（mammalian target of rapamycin，mTOR）信号转导通路抑制剂、脂肪酸合酶抑制剂以及药物递迭系统等药物成为TNBC脑转移患者潜在的治疗方案。虽然Impassion 130研究结果显示，免疫治疗在TNBC脑转移无获益趋势，但基础研究显示放疗联合免疫治疗具有协同作用，目前有多项临床试验（NCT03483012、NCT03449238等）正在探索放疗与免疫治疗在乳腺癌脑转移中的疗效，结果令人期待。本文就TNBC脑转移治疗的研究进展进行综述。

Abstract

Breast cancer has been the second most common solid tumor that metastasizes to the central nervous system after lung cancer. Triple-negative breast cancer (TNBC) has an earlier occurrence and high incidence of brain metastasis with its associated poor prognosis and limited treatment options due to the presence of the blood-brain barrier and lack of targeted drugs. Local treatment

including surgery and radiation therapy

are still the main therapy for brain metastasis. Surgical re

section can not only relieve neurologic impairment of brain metastasis patients

but also can clarify the pathological type. Moreover

surgical resection combined with radiotherapy can improve the prognosis of brain metastasis patients compared to surgery or radiotherapy alone. By now

whole-brain radiation therapy (WBRT) is still considered the gold standard for multiple brain metastases

and meningeal metastases

but it will lead to neurocognitive decline

so hippocampal avoidance is essential. For selected patients with oligometastases

stereotactic radiotherapy has replaced WBRT to reduce cognitive toxicity. However

local treatment of TNBC brain metastasis cannot control the progress of brain metastasis and has significant side effects

so systemic therapy is needed. Chemotherapy drugs such as capecitabine and cisplatin can penetrate the blood-brain barrier

but their efficacy is limited. Therefore

the research and development of new targeted drugs and the exploration of new targets are necessary for TNBC brain metastasis. Research has found that patients carrying germline

BRCA

1/2 mutations have a higher risk of brain metastasis. Currently

the poly adenosine diphosphate ribose polymerase (PARP) inhibitor demonstrated antitumor activity in patients with advanced breast cancer and a germline

BRCA

1/2 mutation

and it can penetrate the blood-brain barrier. The phase Ⅲ trial EMBRACA reported that the PARP inhibitor talazoparib can prolong the progression-free survival of TNBC patients with brain metastasis. In addition

antibody drug conjugates (ADCs) trastuzumab deruxtecan (T-DXd) can also penetrate the blood-brain barrier. Studies such as DEBBRAH have shown that T-DXd has significant therapeutic effects in HER2 positive brain metastasis patients

while research on HER2 low expression patients has not yet reached the endpoint

and its role in TNBC brain metastasis is worth looking forward to. Sacituzumab govitecan (SG) is also an ADC composed of an antibody targeting the human

trophoblast cell-surface antigen 2. The phase Ⅲ ASCENT study showed that in the full population (including 61 patients with brain metastasis)

SG could significantly prolong the progression-free survival of advanced TNBC patients compared to the patients who received chemotherapy. ANG1005

a novel taxane derivative

can cross the blood-brain barrier as well. A multicenter

open-label phase Ⅱ study revealed that ANG1005 could prolong overall survival of patients with brain metastasis. In addition

phosphoinositide3-kinase

(PI3K)/protein kinase (AKT)/mammalian target of rapamycin (mTOR) pathway inhibitors

fatty acid synthase inhibitors

and the drugs with new delivery systems have become potential treatment options for TNBC brain metastasis patients. Although the Impassion 130 reported that no benefit trend for immunotherapy in TNBC brain metastasis

basic research has shown that radiotherapy combined with immunotherapy has a synergistic effect. Currently

multiple clinical trials (NCT03483012

NCT03449238

etc.) are exploring the efficacy of radiotherapy combined with immunotherapy in brain metastasis

and the results are promising. This article reviewed the research progress of TNBC brain metastasis treatment.

关键词

Keywords

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