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中华乳腺病杂志(电子版) ›› 2021, Vol. 15 ›› Issue (06) : 329 -336. doi: 10.3877/cma.j.issn.1674-0807.2021.06.001

所属专题: 总编推荐

专题笔谈

乳腺癌的靶向治疗
刘战涛1, 宋艳秋2,()   
  1. 1. 441000 湖北 襄阳,湖北文理学院附属医院/襄阳市中心医院肿瘤内科;130021 长春,吉林大学第一医院肿瘤内科
    2. 130021 长春,吉林大学第一医院肿瘤内科
  • 收稿日期:2019-07-17 出版日期:2021-12-01
  • 通信作者: 宋艳秋
  • 基金资助:
    吉林省自然科学基金资助项目(20160101028JC)

Targeted therapy for breast cancer

Zhantao Liu1, Yanqiu Song2,()   

  1. 1. Department of Medical Oncology, Xiangyang Central Hospital/Affiliated Hospital of Hubei University of Arts and Science, Xiangyang 441000, China; Department of Medical Oncology, First Hospital of Jilin University, Changchun 130021, China
    2. Department of Medical Oncology, First Hospital of Jilin University, Changchun 130021, China
  • Received:2019-07-17 Published:2021-12-01
  • Corresponding author: Yanqiu Song
引用本文:

刘战涛, 宋艳秋. 乳腺癌的靶向治疗[J]. 中华乳腺病杂志(电子版), 2021, 15(06): 329-336.

Zhantao Liu, Yanqiu Song. Targeted therapy for breast cancer[J]. Chinese Journal of Breast Disease(Electronic Edition), 2021, 15(06): 329-336.

靶向治疗是一种低毒、高选择性的治疗模式。曲妥珠单克隆抗体作为乳腺癌靶向治疗史上最经典的药物,已使成千上万乳腺癌患者受益。随着学者们对肿瘤发生、发展及转移机制的不断探索,靶向治疗药物的研究和应用已取得了突破性进展,为改善乳腺癌患者的生存状况提供了新的治疗策略和途径。笔者就目前不同分子分型乳腺癌的潜在靶点及靶向治疗药物研究进行归纳、总结。

Targeted therapy is a treatment mode with low toxicity and high selectivity. Trastuzumab, as one of the "classic" drugs in the history of targeted therapy for breast cancer, has benefited thousands of breast cancer patients. With the continuous exploration on the mechanism of tumorigenesis, development and metastasis, breakthroughs have been made in the research and application of targeted drugs, which provides a new therapeutic strategy for the improvement of patient survival. In this paper, we summarized the research progress of potential targets and targeted drugs for breast cancer patients.

[1]
Chen W, Zheng R, Baade PD,et al.Cancer statistics in China,2015 [J].CA Cancer J Clin201666(2):115-132.
[2]
李依敏,苏思贞,朱静,等.乳腺癌靶向治疗药物治疗研究进展 [J].山东医药201757(9):107-109.
[3]
中国抗癌协会乳腺癌专业委员会.Her-2阳性乳腺癌临床诊疗专家共识 [J].中国癌症杂志201222(4):314-318.
[4]
江泽飞,邵志敏,徐兵河.人表皮生长因子受体2阳性乳腺癌临床诊疗专家共识2016 [J].中华医学杂志201696(14):1091-1096.
[5]
Curigliano G, Burstein HJ, Winer EP, 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.
[6]
U.S.Food and Drug Administration.FDA grants regular approval to pertuzumab for adjuvant treatment of HER2-positive breast cancer[EB/OL].[2019-07-01].

URL    
[7]
Gianni L, Pienkowski T, Im YH,et al. 5-year analysis of neoadjuvant pertuzumab and trastuzumab in patients with locally advanced, inflammatory, or early-stage HER-2-positive breast cancer (NeoSphere): a multicentre, open-label, phase 2 randomised trial [J]. Lancet Oncol, 2016, 17(6): 791-800.
[8]
von Minckwitz G, Procter M, de Azambuja E,et al.Adjuvant pertuzumab and trastuzumab in eraly HER-2-positive breast cancer [J].N Engl J Med2017377(2):122-131.
[9]
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.
[10]
Loi S,,Giobbe-Hurder A,,Gombos A,et al. PhaseⅠb/Ⅱstudy evaluating the efficacy of pembrolizumab and trastuzumab in patients with trastuzumab-resistant HER-2-positive metastatic breast cancer:Results from the PANACEA (IBCSG45-13/KEYNOTE-014) study[EB/OL].[2019-06-01].

URL    
[11]
Rugo HS, Im SA, Cardoso F,et al. Efficacy of margetuximab vs trastuzumab in patients with pretreated ERBB2 positive advanced breast cancer: a phase 3 randomized clinical trial[J]. JAMA Oncol20217(4):573584.
[12]
vonMinckwitz G, Huang CS, Mano MS,et al. Trastuzumab emtansine for residual invasive HER2-positive breast cancer [J].N Engl J Med2019380(7):617-628.
[13]
Sakai H, Tsurutani J, Iwasa T, et al.HER-2 genomic amplification in circulating tumor DNA and estrogen receptor positivity predict primary resistance to trastuzumab emtansine (T-DM1) in patients with HER-2-positive metastatic breast cancer [J].Breast Cancer201825(5): 605-613.
[14]
Hongbin W, Wenqin W, Yanping X,et al.Aberrant intracellular metabolism of T-DM1 confers T-DM1 resistance in human epidermal growth factor receptor 2-positive gastric cancer cells [J].Cancer Sci2017108(7):1458-1468.
[15]
U.S.Food and Drug Administration.FDA approves new treatment to reduce the risk of breast cancer returning [EB/OL].[2019-07-01].

URL    
[16]
Chan A, Delaloge S, Holmes FA,te al.Neratinib after trastuzumab-based adjuvant therapy in patients with HER-2-positive breast cancer (ExteNET): a multicentre, randomised, double-blind, placebo-controlled,phase 3 trial [J]. Lancet Oncol, 2016, 17(3): 367-377.
[17]
Martin M, Holmes FA, Ejlertsen B, et al. Neratinib after trastuzumab-based adjuvant therapy in HER-2-positive breast cancer (ExteNET): 5-year analysis of a randomised, double-blind, placebocontrolled, phase 3 trial [J]. Lancet Oncol, 2017, 18(12): 1688-1700.
[18]
Fei Ma, Quchang Ouyang, Wei Li,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 Oncol201937(29):2610-2619.
[19]
Xu B, Yan M, Ma F,et al. Pyrotinib plus capecitabine versus lapatinib plus capecitabine for the treatment of HER2-positive metastatic breast cancer (PHOEBE): a multicentre, open-label, randomised, controlled, phase 3 trial [J]. Lancet Oncol202122(3):351-360.
[20]
Zhou Z, Qiao JX, Shetty A,et al. Regulation of estrogen receptor signaling in breast carcinogenesis and breast cancer therapy [J].Cell Mol Life Sci201471(8):1549.
[21]
金科,赵丹,杨林,等.CDK4/6抑制剂联合内分泌治疗对乳腺癌细胞miRNA表达水平的影响 [J]. 现代肿瘤医学201927(5):723-727.
[22]
国家药品监督管理局.2018年审评通过的优先审评药品名单[EB/OL].[2019-07-01].

URL    
[23]
Hortobagyi GN, Stemmer SM, Burris HA, et al. Ribociclib as first line therapy for HR-positive, advanced breast cancer [J]. N Engl J Med, 2016, 375(18):1738-1748.
[24]
Tripathy D, Im SA, Colleoni M, et al. Ribociclib plus endocrine therapy for premenopausal women with hormonereceptor-positive, advanced breast cancer (MONALEESA-7): a randomised phase 3 trial [J]. Lancet Oncol, 2018, 19(7):904-915.
[25]
Slamon DJ, Neven P, Chia S,et al.Phase Ⅲ randomized study of ribociclib and Fulvestrant in hormone receptor-positive,human epidermal growth factor receptor 2-negative advanced breast cancer:MONALEESA-3 [J].J Clin Oncol201836(24):2465-2472.
[26]
Im SA, Lu YS, Bardia A, et al. Overall survival with ribociclib plus endocrine therapy in breast cancer [J]. N Engl J Med2019381(4):307-316.
[27]
O’Leary B, Cutts RJ, Liu Y, et al. The genetic landscape and clonal evolution of breast cancer resistance to palbociclib plus fulvestrant in the PALOMA-3 trial[J]. Cancer Discov, 20188(11):1390-1403.
[28]
Turner NC, Ro J, André F, et al. Palbociclib in hormone-receptor-positive advanced breast cancer [J].N Engl J Med2015373(3):209-219.
[29]
Hares SH, Harvey AJ. mTOR function and therapeutic targeting in breast cancer [J].Am J Cancer Res20177(3):383-404.
[30]
Paplomata E, O’Regan R.The PI3K/AKT/mTOR pathway in breast cancer:targets,trials and biomarkers [J].Ther Adv Med Oncol20146(4):154-166.
[31]
Tesch H, Stoetzer O, Decker T,et al.Efficacy and safety of everolimus plus exemestane in postmenopausal women with hormone receptor-positive, human epidermal growth factor receptor 2-negative locally advanced or metastatic breast cancer: Results of the single-arm, phase ⅢB 4EVER trial [J].Int J Cancer2019144(4):877-885.
[32]
Jones RH, Casbard A, Carucci M,et al. Fulvestrant plus capivasertib versus placebo after relapse or progression on an aromatase inhibitor in metastatic, oestrogen receptor-positive breast cancer (FAKTION): a multicentre, randomised, controlled, phase 2 trial[J]. Lancet Oncol202021(3):345-357.
[33]
Bauer KR, Brown M, Cress RD, et al. Descriptive analysis of estrogen receptor (ER)-negative, progesterone receptor (PR)-negative, and HER2-negative invasive breast cancer, the so-called triple-negative phenotype: a population-based study from the California cancer registry[J]. Cancer2007109(9):1721-1728.
[34]
国家药品监督管理局.首个国产PD-1抗体药物特瑞普利单抗注射液获批上市 [EB/OL].[2018-12-17].

URL    
[35]
黄述斌,侯永微,李松梅,等.乳腺癌组织及间质浸润淋巴细胞中PD-L1的表达及其意义 [J].临床与实验病理学杂志201733(1):63-67.
[36]
Cimino-Mathews A, Thompson E, Taube J M,et a1.PD-L1(B7-H1 ) expression and the immune tumor microenvironment in primary and metastatic breast carcinomas [J].Human Pathol201647(1):52-63.
[37]
Nanda R, Specht J, Dees C,et al.KEYNOTE-012:long-lasting response in a phase Ib study of pembrolizumab for metastatic triple-negative breast cancer (mTNBC) [J]. Cancer Res2017, 77(4 Suppl):P6-10-03.
[38]
Adams S, Loi S, Toppmeyer D, et at. Phase 2 study of pembrolizumab as first-line therapy for PD-L1-positive metastatic triple-negative breast cancer (mTNBC):preliminary data from KEYNOTE-086 cohort B [J].J Clin Oncol201735(15 Suppl):1088.
[39]
Schmid P, Adams S, Rugo HS, et al. Atezolizumab and nab-paclitaxel in advanced triple-negative breast cancer [J]. N Engl J Med2018379(22):2108-2121.
[40]
Schmid P, Rhgo HS, Adams S, et al. Atezolizumab plus nab-paclitaxel as first-line treatment for unresectable, locally advanced or metastatic triple-negative breast cancer (IMpassion 130): updated efficacy, from a randomised,double-blind placebo-controlled,phase 3 trial [J]. Lancet Oncol, 2020, 21(1): 44-59.
[41]
Schmid P, Adams S, Rugo HS,et al.Atezolizumab and nab-paclitaxel in advanced triple-negative breast cancer [J].N Eng J Med2018379(22):2108-2121.
[42]
U.S. Food and Drug Administration. FDA approves atezolizumab for PD-L1 positive unresectable locally advanced or metastatic triple-negative breast cancer[EB/OL].[2019-03-08].

URL    
[43]
Sikov WM, Berry DA, Perou CM,et al. Impact of the addition of carboplatin and/or bevacizumab to neoadjuvant once-per-week paclitaxel followed by dose-dense doxorubicin and cyclophosphamide on pathologic complete response rates in stage Ⅱ to Ⅲ triple-negative breast cancer: CALGB 40603 (Alliance) [J]. J Clin Oncol201533(1):13-21.
[44]
Symonds L, Linden H, Gadi V,et al.Combined targeted therapies for first-line treatment of metastatic triple negative breast cancer-a phase Ⅱ trial of weekly nab-paclitaxel and bevacizumab followed by maintenance targeted therapy with bevacizumab and erlotinib [J].Clin Breast Cancer201919(2):e283-e296.
[45]
Tian S, Quan H, Xie C, et al. YN968D1 is a novel and selective inhibitor of vascular endothelial growth factor receptor-2 tyrosine kinase with potent activity in vitro and in vivo[J]. Cancer Sci2011102(7):1374-1380.
[46]
鲁凯莉.阿帕替尼治疗晚期难治性三阴性乳腺癌的临床疗效探讨 [J].中国处方药201816(6):75-76.
[47]
Li YH, Zhou Y, Wang YW,et al.Comparison of apatinib and capecitabine (Xeloda) with capecitabine (Xeloda) in advanced triple-negative breast cancer as third-line therapy: A retrospective study [J].Medicine (Baltimore)201897 (36):e12222.
[48]
Lee LJ, Alexander B, Schnitt SJ,et al.Clinical outcome of triple negative breast cancer in BRCA1 mutation carriers and noncarriers [J].Cancer2011117( 14): 3093-3100.
[49]
Hu T, Liu C, Li Q,et al. Tapatinib + 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.
[50]
Li T, Wang SB, Lei KJ,et al. Significant response of low-dose apatinib monotherapy in brain metastases of triple-negative breast cancer:A case report [J].Medicine (Baltimore)201998(4):e14182.
[51]
张秀伟,钟文,魏士博,等.三阴性乳腺癌与PARP1表达相关性的Meta分析 [J].现代肿瘤医学201725(6):893-896.
[52]
Vinayak S, Tolaney SM, Schwartzberg L,et al. Open-label clinical trial of niraparib combined with pembrolizumab for treatment of advanced or metastatic triple-negative breast cancer[J]. JAMA Oncol20195(8):1132-1140.
[53]
Pietri E, Conteduca V, Andreis D, et al. Androgen receptor signaling pathways as a target for breast cancer treatment [J]. Endocr Relat Cancer201623(10):R485-498.
[54]
Lyons T, Gucalp A, Arumov A, et al. Safety and tolerability of adjuvant enzalutamide for the treatment of early stage androgen receptor positive (AR+) triple negative breast cancer[J]. J Clin Oncol201836(15 suppl):531.
[55]
Traina TA, Miller K, Yardley DA, et al. Enzalutamide for the treatment of androgen receptor-expressing triple-negative breast cancer [J]. J Clin Oncol, 201836(9):884-890.
[56]
Schmid P, Abraham J, Chan S, et al. AZD5363 plus paclitaxel versus placebo plus paclitaxel as first-line therapy for metastatic triple-negative breast cancer (PAKT): A randomised, double-blind, placebo-controlled, phase Ⅱ trial[J]. J Clin Oncol201836(15 suppl):1007.
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