HER2阳性乳腺癌治疗的研究进展

doi:10.11904/j.issn.1002-3070.2020.01.014

摘要/Abstract

摘要： 人表皮生长因子受体2(HER2)阳性乳腺癌因其侵袭性高、预后差而一直备受关注。随着曲妥珠单抗的应用,早期HER2阳性乳腺癌患者的预后已得到显著改善,由于其仍存在耐药性和不良反应,在标准治疗中加入新的抗HER2药物又成为新的研究重点,这些药物包括帕妥珠单抗、抗体药物偶联物曲妥珠单抗-美坦新(T-DM1)和各种小分子抑制剂(拉帕替尼、来那替尼、吡咯替尼)。同时PD1及PD-L1抑制剂如帕博利珠单抗在HER2阳性乳腺癌中的研究也在进行中,并有部分基础研究和病例报道已经证实了其疗效和安全性。本文旨在对目前HER2阳性乳腺癌的治疗方案和支持HER2阳性乳腺癌治疗的最新证据进行综述。

关键词: 人表皮生长因子受体2, 乳腺癌, 靶向治疗, 进展

Abstract: Human epithelial growth factor receptor 2(HER2)-positive breast cancer has been attracting attention because of its high invasiveness and poor prognosis.With the application of trastuzumab,the prognosis of patients with early HER2-positive breast cancer has been significantly improved.Because of its resistance and adverse reaction,the addition of new anti-HER2 drugs to standard treatment has become a new research project.These drugs include pertuzumab,antibody drug conjugate trastuzumab-emtansine(T-DM1)and various small molecule inhibitors(lapatinib,neratinib and pyrrolidone).At the same time,studies on PD1 and PD-L1 inhibitors such as pabolizumab in HER2-positive breast cancer are underway,some basic studies and case reports have confirmed its efficacy and safety.This article aims to provide an overview of current treatment options for HER2-positive breast cancer and the latest evidence for the treatment of HER2-positive breast cancer.

Key words: HER2, Breast cancer, Targeted therapy, Progression

中图分类号:

R730.5

李国政, 庞达. HER2阳性乳腺癌治疗的研究进展[J]. 实用肿瘤学杂志, 2020, 34(1): 74-78.

LI Guozheng, PANG Da. Progression in the treatment of HER2-positive breast cancer[J]. Journal of Practical Oncology, 2020, 34(1): 74-78.

参考文献

1 Harbeck N,Gnant M.Breast cancer[J].Lancet,2017,389(1):1134-1150.
2 Zhang Q,Chen J,Yu X,et al.Survival benefit of anti-HER2 therapy after whole-brain radiotherapy in HER2-positive breast cancer patients with brain metastasis[J].Breast Cancer,2016,23(5):732-739.
3 Wong H,Leung R,Kwong A,et al.Integrating molecular mechanisms and clinical evidence in the management of trastuzumab resistant or refractory HER2+ metastatic breast cancer[J].Oncologist,2011,16(11):1535-1546.
4 Goldhirsch A,Gelber RD,Piccart-Gebhart MJ,et al.2 years versus 1 year of adjuvant trastuzumab for HER2-positive breast cancer(HERA):an open-label,randomised controlled trial[J].Lancet,2013,382(9897):1021-1028.
5 McCaw ZR,Jiang F,Wei LJ.Trastuzumab therapy for 9 weeks vs 1 year for human epidermal growth factor receptor 2-positive breast cancer[J].JAMA Oncol,2019,5(1):117-118.
6 Curigliano G,Burstein HJ,P Winer E,et al.De-escalating and escalating treatments for early-stage breast cancer:the St.Gallen International Expert Consensus Conference on the Primary Therapy of Early Breast Cancer 2017[J].Ann Oncol,2017,28(8):1700-1712.
7 Marty M,Cognetti F,Maraninchi D,et al.Randomized phase II trial of the efficacy and safety of trastuzumab combined with docetaxel in patients with human epidermal growth factor receptor 2-positive metastatic breast cancer administered as first-line treatment:the M77001 study group[J].J Clin Oncol,2005,23(19):4265-4274.
8 Slamon DJ,Leyland B,Shak S,et al.Use of chemotherapy plus a monoclonal antibody against HER2 for metastaticbreast cancer that overexpresses HER2[J].N Engl J Med,2001,344(11):783-792.
9 Andersson M,Lidbrink E,Bjerre K,et al.Phase III randomized study comparing docetaxel plus trastuzumab with vinorelbine plus trastuzumab as first-line therapy of metastatic or locally advanced human epidermal growth factor receptor 2-positivebreast cancer:the HERNATA study[J].J Clin Oncol,2011,29(3):264-271.
10 Gianni L,Eiermann W,Semiglazov V,et al.Neoadjuvant chemotherapy with trastuzumab followed by adjuvant trastuzumab versus neoadjuvant chemotherapy alone,in patients with HER2-positive locally advanced breast cancer(the NOAH trial):a randomised controlled superiority trial with a parallel HER2-negative cohort[J].Lancet,2010,375(9712):377-384.
11 Buzdr AU,Suman VJ,Meric-Bernstam F,et al.Fliorouracil,epirubicin,and cyclophosphamide(FEC-75)followed by paclitaxel plus trastuzumab versus paclitaxel plus trastuzumab followed by FEC-75 plus trastuzumab as neoadjuvant treatment for patients with HER2-positive breast cancer(Z1041):a randomized,controlled,phase 3 trial[J].Lancet Oncol,2013,14(13):1317-1325.
12 Nami B,Maadi H,Wang Z.Mechanisms underlying the action and synergism of trastuzumab and pertuzumab in targeting HER2-positive breast cancer[J].Cancers(Basel),2018,10(10):342-363.
13 von Minckwitz G,Procter M,de Azambuja E,et al.Adjuvant pertuzumab and trastuzumab in early HER2-positive breast cancer[J].N Engl J Med,2017,377(2):122-131.
14 Irabor OC,Kerry VB,Matton J,et al.Leveraging the global health service partnership model for workforce development in global radiation oncology[J].J Glob Oncol,2018,(4):1-8.
15 Swain SM,Baselga J,Kim SB,et al.Pertuzumab,trastuzumab,and docetaxel in HER2-positive metastatic breast cancer[J].N Engl J Med,2015,372(8):724-734.
16 Bartsch R,Bergen E.ASCO 2018:highlights in HER2-positive metastatic breast cancer[J].Memo,2018,11(4):280-283.
17 Gianni L,Pienkowski T,Im YH,et al.Efficacy and safety of neoadjuvant pertuzumab and trastuzumab in women with locally advanced,inflammatory,or early HER2-positive breast cancer(NeoSphere):a randomised multicentre,open-label,phase 2 trial[J].Lancet Oncol,2012,13(1):25-32.
18 Schneeweiss A,Chia S,Hickish T,et al.Pertuzumab plus trastuzumab in combination with standard neoadjuvant anthracycline-containing and anthracycline-free chemotherapy regimens in patients with HER2-positive early breast cancer:a randomized phase II cardiac safety study(TRYPHAENA)[J].Ann Oncol,2013,24(9):2278-2284.
19 宋金洁,王涛,边莉,等.曲妥珠单抗联合蒽环类药物应用于Her-2阳性乳腺癌的新辅助治疗初步临床研究[J].实用肿瘤学杂志,2013,27(2):97-100.
20 Swain SM,Ewer MS,Viale G,et al.Pertuzumab,trastuzumab,and standard anthracycline-and taxane-based chemotherapy for the neoadjuvant treatment of patients with HER2-positive localized breast cancer(BERENICE):a phase II,open-label,multicenter,multinational cardiac safety study[J].Ann Oncol,2018,29(3):646-653.
21 Geyer CE Jr,Huang CS.KATHERINE Trial:Adjuvant ado-trastuzumab emtansine vs trastuzumab in early-stage HER2-positive breast cancer[C].America:Sabcs San Antonio Breast Cancer Symposium,2018.
22 Minckwitz G,Huang C,Mano M,et al.Trastuzumab emtansine for residual invasive HER2-positive breast cancer[J].N Engl J Med,2019,380:617-628.
23 Verma S,Miles D,Gianni L,et al.Trastuzumab emtansine for HER2-positive advanced breast cancer[J].New Eng J Med,2012,367(19):1783-1791.
24 Perez EA,Barrios C,Eiermann W,et al.Trastuzumab emtansinewith or without pertuzumab versus trastuzumab plus taxane for hu-man epidermal growth factor receptor 2-positive,advanced breastcancer:primary results from the phase Ⅲ MARIANNE study[J].J Clin Oncol,2017,35(2):141-148.
25 Okines AF.T-DM1 in the neo-adjuvant treatment of HER2-positive breast cancer:impact of the KRISTINE(TRIO-021)Trial[J].Rev Recent Clin Trials,2017,12(3):216-222.
26 杜歌,江泽飞.拉帕替尼在乳腺癌中的应用及其耐药机制研究现状[J].实用肿瘤学杂志,2015,29(4):376-379.
27 Ogawa L,Lindquist D.Dual HER2 suppression with lapatinib plus trastuzumab for metastatic inflammatory breast cancer:a case report of prolonged stable disease[J].Case Rep Oncol,2018,11(3):855-860.
28 Johnston SRD,Hegg R,Im SA,et al.Phase III,randomized study of dual human epidermal growth factor receptor 2(HER2)blockade with Lapatinib plus Trastuzumab in combination with an aromatase inhibitor in postmenopausal women with HER2-positive,hormone receptor-positive metastatic breast cancer:ALTERNATIVE[J].J Clin Oncol,2018,36(8):741-748.
29 Kourie HR,Chaix M,Gombos A,et al.Pharmacodynamics,pharmacokinetics and clinical efficacy of neratinib in HER2-positive breast cancer and breast cancer with HER2 mutations[J].Expert Opin Drug Metab Toxicol,2016,12(8):947-957.
30 Martin M,Holmes FA,Ejlertsen B,et al.Neratinib after trastuzumab-based adjuvant therapy in HER2-positive breast cancer(ExteNET):5-year analysis of a randomised,double-blind,placebo-controlled,phase 3 trial[J].Lancet Oncol,2017,18(12):1688-1700.
31 Park JW,Liu MC,Yee D,et al.Adaptive randomization of neratinib in early breast cancer[J].N Engl J Med,2016,375(1):11-22.
32 Jacobs SA,Robidoux A,Garcia J,et al.A phase II randomized trial evaluating neoadjuvant therapy with weekly paclitaxel(P)plus neratinib(N)or trastuzumab(T)or neratinib and trastuzumab(N+T)followed by doxorubicin and cyclophosphamide(AC)with postoperative T in women with locally advanced HER2-positive breast cancer[J].Cancer Research,2016,76(4 Supplement):4.
33 Ma F,Ouyang Q,Li W,et al.Pyrotinib or lapatinib combined with capecitabine in HER2-positive metastatic breast cancer with prior taxanes,anthracyclines,and/or trastuzumab:A randomized,phase II study[J].J Clin Oncol,2019,37(29):2610-2619.
34 Pardoll DM.The blockade of immune checkpoints in cancer immunotherapy[J].Nat Rev Cancer,2012,12(4):252-264.
35 De La Cruz LM,Czerniecki BJ.Immunotherapy for breast cancer is finally at the doorstep:immunotherapy in breast cancer[J].Ann Surg Oncol,2018,25(10):2852-2857.
36 Bian L,Wang T,Zhang SH,et al.Remarkable response with pembrolizumab plus albumin-bound paclitaxel in 2 cases of HER2-positive metastatic breast cancer who have failed to multi-anti-HER2 targeted therapy[J].Cancer Biol Ther,2018,19(4):292-295.

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