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

参考文献 60

1	Siegel RL, Miller KD, Jemal A. Cancer statistics, 2020[J]. CA Cancer J Clin, 2020, 70(1): 7-30.
2	Fecci PE, Champion CD, Hoj J, et al. The evolving modern management of brain metastasis[J]. Clin Cancer Res, 2019, 25(22): 6570-6580.
3	Waks AG, Winer EP. Breast cancer treatment: a review[J]. JAMA, 2019, 321(3): 288-300.
4	Xing F, Liu Y, Sharma S, et al. Activation of the c-met pathway mobilizes an inflammatory network in the brain microenvironment to promote brain metastasis of breast cancer[J]. Cancer Res, 2016, 76(17): 4970-4980.
5	Sirkisoon SR, Carpenter RL, Rimkus T, et al. TGLI1 transcription factor mediates breast cancer brain metastasis via activating metastasis-initiating cancer stem cells and astrocytes in the tumor microenvironment[J]. Oncogene, 2020, 39(1): 64-78.
6	Choy C, Ansari KI, Neman J, et al. Cooperation of neurotrophin receptor TrkB and Her2 in breast cancer cells facilitates brain metastases[J]. Breast Cancer Res, 2017, 19(1): 51.
7	Witzel I, Oliveira-Ferrer L, Pantel K, et al. Breast cancer brain metastases: biology and new clinical perspectives[J]. Breast Cancer Res, 2016, 18(1): 8.
8	Ramakrishna N, Temin S, Chandarlapaty S, et al. Recommendations on disease management for patients with advanced human epidermal growth factor receptor 2-positive breast cancer and brain metastases: ASCO clinical practice guideline update[J]. J Clin Oncol, 2018, 36(27): 2804-2807.
9	Osswald M, Blaes J, Liao YX, et al. Impact of blood-brain barrier integrity on tumor growth and therapy response in brain metastases[J]. Clin Cancer Res, 2016, 22(24): 6078-6087.
10	Stemmler HJ, Schmitt M, Willems A, et al. Ratio of trastuzumab levels in serum and cerebrospinal fluid is altered in HER2-positive breast cancer patients with brain metastases and impairment of blood-brain barrier[J]. Anticancer Drugs, 2007, 18(1): 23-28.
11	Bonneau C, Paintaud G, Trédan O, et al. Phase Ⅰ feasibility study for intrathecal administration of trastuzumab in patients with HER2 positive breast carcinomatous meningitis[J]. Eur J Cancer, 2018, 95: 75-84.
12	Park YH, Park MJ, Ji SH, et al. Trastuzumab treatment improves brain metastasis outcomes through control and durable prolongation of systemic extracranial disease in HER2-overexpressing breast cancer patients[J]. Br J Cancer, 2009, 100(6): 894-900.
13	Kodack DP, Chung E, Yamashita H, et al. Combined targeting of HER2 and VEGFR2 for effective treatment of HER2-amplified breast cancer brain metastases[J]. Proc Natl Acad Sci USA, 2012, 109(45): E3119-E3127.
14	Falchook GS, Moulder SL, Wheler JJ, et al. Dual HER2 inhibition in combination with anti-VEGF treatment is active in heavily pretreated HER2-positive breast cancer[J]. Ann Oncol, 2013, 24(12): 3004-3011.
15	Swain SM, Miles D, Kim SB, et al. Pertuzumab, trastuzumab, and docetaxel for HER2-positive metastatic breast cancer (CLEOPATRA): end-of-study results from a double-blind, randomised, placebo-controlled, phase 3 study[J]. Lancet Oncol, 2020, 21(4): 519-530.
16	Swain SM, Baselga J, Miles D, et al. Incidence of central nervous system metastases in patients with HER2-positive metastatic breast cancer treated with pertuzumab, trastuzumab, and docetaxel: results from the randomized phase Ⅲ study CLEOPATRA[J]. Ann Oncol, 2014, 25(6): 1116-1121.
17	Krop IE, Lin NU, Blackwell K, et al. Trastuzumab emtansine (T-DM1) versus lapatinib plus capecitabine in patients with HER2-positive metastatic breast cancer and central nervous system metastases: a retrospective, exploratory analysis in EMILIA[J]. Ann Oncol, 2015, 26(1): 113-119.
18	Montemurro F, Ellis P, Delaloge S, et al. Safety and efficacy of trastuzumab emtansine (T-DM1) in 399 patients with central nervous system metastases: Exploratory subgroup analysis from the KAMILLA study[C]//Proceedings of the 2016 San Antonio Breast Cancer Symposium, December6-10, 2016.
	Antonio San, TX. Philadelphia: AACR. Cancer Res, 2017, 77(4): P1-12-10.
19	Emens LA, Esteva FJ, Beresford M, et al. Overall survival (OS) in KATE2, a phase Ⅱ study of programmed death ligand 1 (PD-L1) inhibitor atezolizumab (atezo)+trastuzumab emtansine (T-DM1) vs placebo (pbo)+T-DM1 in previously treated HER2+ advanced breast cancer (BC)[J]. Ann Oncol, 2019, 30: v104.
20	Dong RR, Ji JL, Liu H, et al. The evolving role of trastuzumab emtansine (T-DM1) in HER2-positive breast cancer with brain metastases[J]. Crit Rev Oncol Hematol, 2019, 143: 20-26.
21	Stumpf PK, Cittelly DM, Robin TP, et al. Combination of trastuzumab emtansine and stereotactic radiosurgery results in high rates of clinically significant radionecrosis and dysregulation of aquaporin-4[J]. Clin Cancer Res, 2019, 25(13): 3946-3953.
22	Modi SN, Saura C, Yamashita T, et al. Trastuzumab deruxtecan in previously treated HER2-positive breast cancer[J]. N Engl J Med, 2020, 382(7): 610-621.
23	Banerji U, van Herpen CML, Saura C, et al. Trastuzumab duocarmazine in locally advanced and metastatic solid tumours and HER2-expressing breast cancer: a phase 1 dose-escalation and dose-expansion study[J]. Lancet Oncol, 2019, 20(8): 1124-1135.
24	Bachelot T, Romieu G, Campone M, et al. Lapatinib plus capecitabine in patients with previously untreated brain metastases from HER2-positive metastatic breast cancer (LANDSCAPE): a single-group phase 2 study[J]. Lancet Oncol, 2013, 14(1): 64-71.
25	Awada A, Colomer R, Inoue K, et al. Neratinib plus paclitaxel vs trastuzumab plus paclitaxel in previously untreated metastatic ERBB2-positive breast cancer: the NEfERT-T randomized clinical trial[J]. JAMA Oncol, 2016, 2(12): 1557-1564.
26	Freedman RA, Gelman RS, Anders CK, et al. TBCRC 022: a phase Ⅱ trial of neratinib and capecitabine for patients with human epidermal growth factor receptor 2-positive breast cancer and brain metastases[J]. J Clin Oncol, 2019, 37(13): 1081-1089.
27	Saura C, Oliveira M, Feng YH, et al. Neratinib plus capecitabine versus lapatinib plus capecitabine in HER2-positive metastatic breast cancer previously treated with ≥ 2 HER2-directed regimens: phase Ⅲ NALA trial[J]. J Clin Oncol, 2020, 38(27): 3138-3149.
28	Murthy RK, Loi S, Okines A, et al. Tucatinib, trastuzumab, and capecitabine for HER2-positive metastatic breast cancer[J]. N Engl J Med, 2020, 382(7): 597-609.
29	Borges VF, Ferrario C, Aucoin N, et al. Tucatinib combined with ado-trastuzumab emtansine in advanced ERBB2/HER2-positive metastatic breast cancer: a phase 1b clinical trial[J]. JAMA Oncol, 2018, 4(9): 1214-1220.
30	Jiang ZF, Yan M, Hu XC, et al. Pyrotinib combined with capecitabine in women with HER2+ metastatic breast cancer previously treated with trastuzumab and taxanes: a randomized phase Ⅲ study[J]. J Clin Oncol, 2019, 37(): 1001.
31	Anders CK, Le Rhun E, Bachelot TD, et al. A phase Ⅱ study of abemaciclib in patients (pts) with brain metastases (BM) secondary to HR+, HER2- metastatic breast cancer (MBC)[J]. J Clin Oncol, 2019, 37(): 1017.
32	Litton JK, Rugo HS, Ettl J, et al. Talazoparib in patients with advanced breast cancer and a germline BRCA mutation[J]. N Engl J Med, 2018, 379(8): 753-763.
33	Jung J, Lee SH, Park M, et al. Discordances in ER, PR, and HER2 between primary breast cancer and brain metastasis[J]. J Neurooncol, 2018, 137(2): 295-302.
34	Razavi P, dos Anjos CH, Brown DN, et al. Molecular profiling of ER+ metastatic breast cancers to reveal association of genomic alterations with acquired resistance to CDK4/6 inhibitors[J]. J Clin Oncol, 2019, 37(): 1009.
35	Ippen FM, Alvarez-Breckenridge CA, Kuter BM, et al. The dual PI3K/mTOR pathway inhibitor GDC-0084 achieves antitumor activity in PIK3CA-mutant breast cancer brain metastases[J]. Clin Cancer Res, 2019, 25(11): 3374-3383.
36	Ippen FM, Grosch JK, Subramanian M, et al. Targeting the PI3K/Akt/mTOR pathway with the pan-Akt inhibitor GDC-0068 in PIK3CA-mutant breast cancer brain metastases[J]. Neuro Oncol, 2019, 21(11): 1401-1411.
37	Shah N, Mohammad AS, Saralkar P, et al. Investigational chemotherapy and novel pharmacokinetic mechanisms for the treatment of breast cancer brain metastases[J]. Pharmacol Res, 2018, 132: 47-68.
38	Melisko ME, Assefa M, Hwang J, et al. Phase Ⅱ study of irinotecan and temozolomide in breast cancer patients with progressing central nervous system disease[J]. Breast Cancer Res Treat, 2019, 177(2): 401-408.
39	Jung SU, Jeon CW, Choi JH. Long-term survival with eribulin monotherapy after whole brain radiation therapy in a patient with brain metastasis from breast cancer[J]. Asian J Surg, 2020, 43(10): 1008-1009.
40	Byun KD, Ahn SG, Baik HJ, et al. Eribulin mesylate combined with local treatment for brain metastasis from breast cancer: two case reports[J]. J Breast Cancer, 2016, 19(2): 214-217.
41	Matsuoka H, Tsurutani J, Tanizaki J, et al. Regression of brain metastases from breast cancer with eribulin: a case report[J]. BMC Res Notes, 2013, 6: 541.
42	Nieder C, Aandahl G, Dalhaug A. A case of brain metastases from breast cancer treated with whole-brain radiotherapy and eribulin mesylate[J]. Case Rep Oncol Med, 2012, 2012: 537183.
43	Chang AY, Ying XX. Brain metastases from breast cancer and response to treatment with eribulin: a case series[J]. Breast Cancer (Auckl), 2015, 9: 19-24.
44	Catania G, Malaguti P, Gasparro S, et al. Activity of eribulin mesylate in brain metastasis from breast cancer: a stone in a pond?[J]. Oncology, 2018, 94(): 29-33.
45	Hu T, Liu CW, Li QH, et al. Apatinib + CPT-11 + S-1 for treatment of refractory brain metastases in patient with triple-negative breast cancer: case report and literature review[J]. Medicine (Baltimore), 2018, 97(15): e0349.
46	Lin NU, Gelman RS, Younger WJ, et al. Phase Ⅱ trial of carboplatin (C) and bevacizumab (BEV) in patients (pts) with breast cancer brain metastases (BCBM)[J]. J Clin Oncol, 2013, 31(): 513.
47	Lu YS, Chen TW, Lin CH, et al. Bevacizumab preconditioning followed by etoposide and cisplatin is highly effective in treating brain metastases of breast cancer progressing from whole-brain radiotherapy[J]. Clin Cancer Res, 2015, 21(8): 1851-1858.
48	Kumthekar P, Tang SC, Brenner AJ, et al. ANG1005, a brain-penetrating peptide-drug conjugate, shows activity in patients with breast cancer with leptomeningeal carcinomatosis and recurrent brain metastases[J]. Clin Cancer Res, 2020, 26(12): 2789-2799.
49	Perez EA, Awada A, O'Shaughnessy J, et al. Etirinotecan pegol (NKTR-102) versus treatment of physician's choice in women with advanced breast cancer previously treated with an anthracycline, a taxane, and capecitabine (BEACON): a randomised, open-label, multicentre, phase 3 trial[J]. Lancet Oncol, 2015, 16(15): 1556-1568.
50	Cortés J, Rugo HS, Awada A, et al. Prolonged survival in patients with breast cancer and a history of brain metastases: results of a preplanned subgroup analysis from the randomized phase Ⅲ BEACON trial[J]. Breast Cancer Res Treat, 2017, 165(2): 329-341.
51	Goldberg SB, Schalper KA, Gettinger SN, et al. Pembrolizumab for management of patients with NSCLC and brain metastases: long-term results and biomarker analysis from a non-randomised, open-label, phase 2 trial[J]. Lancet Oncol, 2020, 21(5): 655-663.
52	Kluger HM, Chiang V, Mahajan A, et al. Long-term survival of patients with melanoma with active brain metastases treated with pembrolizumab on a phase Ⅱ trial[J]. J Clin Oncol, 2019, 37(1): 52-60.
53	Schmid P, Rugo HS, Adams S, et al. Atezolizumab plus nab-paclitaxel as first-line treatment for unresectable, locally advanced or metastatic triple-negative breast cancer (IMpassion130): updated efficacy results from a randomised, double-blind, placebo-controlled, phase 3 trial[J]. Lancet Oncol, 2020, 21(1): 44-59.
54	Liu JQ, Jiang ZF, Li Q, et al. Efficacy and safety of anti-PD-1 antibody SHR-1210 combined with apatinib in patients with advanced triple-negative breast cancer[J]. J Clin Oncol, 2019, 37(): 1066.
55	Niwińska A, Murawska M, Pogoda K. Breast cancer subtypes and response to systemic treatment after whole-brain radiotherapy in patients with brain metastases[J]. Cancer, 2010, 116(18): 4238-4247.
56	Niwińska A. Brain metastases as site of first and isolated recurrence of breast cancer: the role of systemic therapy after local treatment[J]. Clin Exp Metastasis, 2016, 33(7): 677-685.
57	Miller JA, Kotecha R, Ahluwalia MS, et al. Overall survival and the response to radiotherapy among molecular subtypes of breast cancer brain metastases treated with targeted therapies[J]. Cancer, 2017, 123(12): 2283-2293.
58	Sperduto PW, Kased N, Roberge D, et al. Summary report on the graded prognostic assessment: an accurate and facile diagnosis-specific tool to estimate survival for patients with brain metastases[J]. J Clin Oncol, 2012, 30(4): 419-425.
59	Subbiah IM, Lei XD, Weinberg JS, et al. Validation and development of a modified breast graded prognostic assessment as a tool for survival in patients with breast cancer and brain metastases[J]. J Clin Oncol, 2015, 33(20): 2239-2245.
60	Griguolo G, Jacot W, Kantelhardt E, et al. External validation of Modified Breast Graded Prognostic Assessment for breast cancer patients with brain metastases: a multicentric European experience[J]. Breast, 2018, 37: 36-41.

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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