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

作　　者：曹晓珊 杨蓓蓓 丛斌斌 刘红 CAO Xiaoshan;YANG Beibei;CONG Binbin;LIU Hong(Tianjin Medical University Cancer Institute&Hospital,National Clinical Research Center for Cancer,Tianjin’s Clinical Research Center for Cancer,Key Laboratory of Breast Cancer Prevention and Therapy,Tianjin Medical University,Ministry of Education,Key Laboratory of Cancer Prevention and Therapy,Tianjin 300181,China;Breast Cancer Centre,Shandong Cancer Hospital and Institute,Shandong First Medical University and Shandong Academy of Medical Sciences,Jinan 250117,Shandong Province,China)

机构地区：[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

出　　处：《中国癌症杂志》2024年第8期777-784,共8页China Oncology

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BRCA1/2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BRCA1/2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�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 resection 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 BRCA1/2 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 BRCA1/2 mutation,and it can penetrate the blood-brain barrier.The phaseⅢtrial 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 deruxtec

关 键 词：三阴性乳腺癌 脑转移 局部治疗 化疗 靶向治疗 免疫治疗 

分 类 号：R737.9[医药卫生—肿瘤]