乳腺癌脑转移系统治疗的研究进展

doi:10.3969/j.issn.1674-8115.2021.05.019

摘要/Abstract

摘要：

乳腺癌是女性发病率最高的恶性肿瘤，10%~20%的晚期乳腺癌患者会发生脑转移。近年来随着系统治疗的快速发展，乳腺癌颅外病灶得以有效控制，患者的生存期得以延长，而发生脑转移的可能性也在增加；影像学技术的进步以及常规影像学监测的普及也增加了颅内病灶的检出率。这些都使得乳腺癌脑转移在临床上越来越常见。许多化学治疗药物不能透过血脑屏障。对于发生脑转移的患者，其可选择的治疗方法较少，生存期较短并且生活质量较低。该文着重阐述近年来乳腺癌脑转移系统治疗的研究进展，旨在为该类疾病的基础研究和临床实践提供参考。

关键词: 乳腺癌, 脑转移, 系统治疗, 人表皮生长因子受体2, 靶向治疗

Abstract:

Breast cancer is one of the most common malignancies in women. Brain metastases occur in approximately 10%–20% of patients with advanced breast cancer. In recent years, with the rapid progress of systemic treatment, extracranial lesions have been effectively controlled and the survival time of patients with breast cancer have been prolonged. Thus the possibility of developing brain metastases has been increased. Moreover, advances in modern diagnostic imaging technology and the routine surveillance of cancer patients have increased the detection rate of brain lesions. Based on the above two aspects, the breast cancer brain metastases (BCBM) have become increasingly common in the clinical settings. Because many chemotherapeutic drugs can not penetrate the blood-brain barrier, the patients with brain metastases have less treatment options, worse survival outcomes and lower quality of life. This article focuses on the recent advances in systemic treatment for BCBM, aiming to provide reference for basic research and clinical practices of this disease.

Key words: breast cancer, brain metastasis, systemic therapy, human epidermal growth factor receptor 2 (HER2), targeted therapy

中图分类号:

R737.9

张佳玲, 张凤春, 徐迎春. 乳腺癌脑转移系统治疗的研究进展[J]. 上海交通大学学报(医学版), 2021, 41(5): 671-677.

Jia-ling ZHANG, Feng-chun ZHANG, Ying-chun XU. Research progress in the systemic treatment for breast cancer with brain metastasis[J]. JOURNAL OF SHANGHAI JIAOTONG UNIVERSITY (MEDICAL SCIENCE), 2021, 41(5): 671-677.

图/表 1

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Drug	Molecular weight/（g·mol^-1）	Target	Published trail	Outcome	Reference
Lapatinib	581.1	EGFR/HER2	LANDSCAPE	ORR of CNS was 65.9% in BCBM patients treated with lapatinib plus capecitabine	[24]
Neratinib	557.1	EGFR/HER2/HER4	NEfERT-T	Recurrence rate of symptomatic or progressive CNS disease was 8.3% vs 17.3% in neratinib-paclitaxel group and trastuzumab-paclitaxel group, respectively	[25]
			TBCRC022	ORR of CNS was 49% and PFS was 5.5 months in lapatinib-na?ve patients with progressive brain metastases treated with neratinib plus capecitabine	[26]
			NALA	Overall cumulative incidence of intervention for symptomatic CNS disease was 22.8% vs 29.2% for neratinib-capecitabine and lapatinib-capecitabine, respectively	[27]
Tucatinib	480.5	HER2	HER2CLIMB	PFS was 7.6 vs 5.4 months and PFS at 1 year was 24.9% vs 0 in tucatinib-combination group and placebo-combination group, respectively	[28]
Pyrotinib	583.1	EGFR/HER2/HER4	NCT02973737	CNS progression rate was 73.3% vs 87.5%, and time to CNS progression was 168.0 d vs 127.0 d in pyrotinib-capecitabine group and placebo-capecitabine group, respectively	[30]
Abemaciclib	506.6	CDK4/6	NCT02308020	PFS was 4.4 months, and intracranial clinical benefit rate was 25% in BCBM patients treated with abemaciclib	[31]
Talazoparib	380.4	PARP1/2	EMBRACA	PFS was 8.6 vs 5.6 months, and ORR was 62.6% vs 27.2% in patients treated with talazoparib and physician's choice, respectively	[32]

Drug	Molecular weight/（g·mol^-1）	Target	Published trail	Outcome	Reference
Lapatinib	581.1	EGFR/HER2	LANDSCAPE	ORR of CNS was 65.9% in BCBM patients treated with lapatinib plus capecitabine	[24]
Neratinib	557.1	EGFR/HER2/HER4	NEfERT-T	Recurrence rate of symptomatic or progressive CNS disease was 8.3% vs 17.3% in neratinib-paclitaxel group and trastuzumab-paclitaxel group, respectively	[25]
			TBCRC022	ORR of CNS was 49% and PFS was 5.5 months in lapatinib-na?ve patients with progressive brain metastases treated with neratinib plus capecitabine	[26]
			NALA	Overall cumulative incidence of intervention for symptomatic CNS disease was 22.8% vs 29.2% for neratinib-capecitabine and lapatinib-capecitabine, respectively	[27]
Tucatinib	480.5	HER2	HER2CLIMB	PFS was 7.6 vs 5.4 months and PFS at 1 year was 24.9% vs 0 in tucatinib-combination group and placebo-combination group, respectively	[28]
Pyrotinib	583.1	EGFR/HER2/HER4	NCT02973737	CNS progression rate was 73.3% vs 87.5%, and time to CNS progression was 168.0 d vs 127.0 d in pyrotinib-capecitabine group and placebo-capecitabine group, respectively	[30]
Abemaciclib	506.6	CDK4/6	NCT02308020	PFS was 4.4 months, and intracranial clinical benefit rate was 25% in BCBM patients treated with abemaciclib	[31]
Talazoparib	380.4	PARP1/2	EMBRACA	PFS was 8.6 vs 5.6 months, and ORR was 62.6% vs 27.2% in patients treated with talazoparib and physician's choice, respectively	[32]

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