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中华乳腺病杂志(电子版) ›› 2021, Vol. 15 ›› Issue (05) : 302 -306. doi: 10.3877/cma.j.issn.1674-0807.2021.05.006

综述

血管内皮生长因子在炎性乳腺癌中的应用
张梦璐1, 邢泽宇1, 王昕1, 刘嘉琦1, 刘刚1, 王翔1,()   
  1. 1. 100021 北京,国家癌症中心/国家肿瘤临床医学研究中心/中国医学科学院北京协和医学院肿瘤医院乳腺外科
  • 收稿日期:2020-12-07 出版日期:2021-10-01
  • 通信作者: 王翔
  • 基金资助:
    中国医学科学院医学与健康科技创新工程,重大协同创新项目(2016-12M-1-001); 中国医学科学院医学与健康科技创新工程,协同创新团队项目(2017-12M-3-004); 北京市科学技术委员会项目(D161100000816003); 中央高校基本科研业务费专项资金项目(3332020026)

Application of vascular endothelial growth factor in inflammatory breast cancer

Menglu Zhang1, Zeyu Xing1, Xin Wang1   

  • Received:2020-12-07 Published:2021-10-01
引用本文:

张梦璐, 邢泽宇, 王昕, 刘嘉琦, 刘刚, 王翔. 血管内皮生长因子在炎性乳腺癌中的应用[J]. 中华乳腺病杂志(电子版), 2021, 15(05): 302-306.

Menglu Zhang, Zeyu Xing, Xin Wang. Application of vascular endothelial growth factor in inflammatory breast cancer[J]. Chinese Journal of Breast Disease(Electronic Edition), 2021, 15(05): 302-306.

炎性乳腺癌侵袭性强,治疗敏感性差,严重危害患者生命健康。乳腺癌是一种具有高度血管生成依赖性的肿瘤,血管内皮生长因子在调控其血管生成的过程中发挥了重要作用。炎性乳腺癌细胞常过度表达血管内皮生长因子,且这种高表达与肿瘤大小、腋窝淋巴结转移及不良预后密切相关。笔者详细分析了血管内皮生长因子在炎性乳腺癌中的生物学作用及临床应用价值,并就抗血管内皮生长因子信号通路在炎性乳腺癌靶向治疗中的研究进展进行综述。

表1 抗VEGF信号通路的炎性乳腺癌靶向治疗临床试验汇总
研究者 试验类型 样本量(例) 纳入条件 治疗方案 试验结果
贝伐珠单克隆抗体          
  Bertucci等[36] 2期、多中心、单臂试验 100 HER-2阴性、炎性乳腺癌,未伴远处转移 新辅助治疗:1~4周期(FEC + Bev 15 mg/kg), 5~8周期(TH + Bev 15 mg/kg) pCR率为19%, 3年DFS为57%,3年OS为75%
  Pierga等[37,38] 2期、多中心、单臂试验 52 HER-2阳性、炎性乳腺癌,未伴远处转移 新辅助治疗:1~4周期(FEC + Bev 15 mg/kg), 5~8周期(T + Bev 15 mg/kg) pCR率为63.5%,3年DFS为68%,3年OS为90%
  Nahleh等[39] 2期、非盲、随机对照试验 211 HER-2阴性、炎性乳腺癌或局部晚期乳腺癌 分为3组:A组98例接受Bev 10 mg/kg 6周期新辅助治疗序贯P-AC方案化疗、B组62例接受P-AC方案化疗、C组51例接受AC-P方案化疗 接受Bev治疗的患者与未接受Bev治疗的患者比较:pCR率,36%比21%, P= 0.019; 3年OS,86%比87%, P= 0.64
  Palazzo等[40] 2期、单臂试验 34 原发或复发炎性乳腺癌,未伴远处转移 新辅助治疗:P + CBP + Bev 15 mg/kg + C pCR率为29%,5年DFS为58%,5年OS为72%
SU5416          
  Overmoyer等[44] 1期转化试验 18 B期或Ⅳ期炎性乳腺癌,无蒽环类药物治疗史 新辅助治疗:A + SU5416共5周期 中位DFS为31月;4例出现充血性心力衰竭
帕唑帕尼          
  Cristofanilli等[45] 2期、多中心、随机对照试验 队列1: 76
队列2: 88
HER-2阳性、炎性乳腺癌 队列1:以1∶1的比例随机分为2组,分别接受拉帕替尼1 500 mg +安慰剂或拉帕替尼1 500 mg +帕唑帕尼800 mg,每天1次
队列2:以5∶5∶2的比例随机分为3组,分别接受拉帕替尼单药1 500 mg、拉帕替尼1 000 mg +帕唑帕尼400 mg或帕唑帕尼单药800 mg治疗,每天1次
队列1:拉帕替尼组和联合组ORR分别为29%、45%;中位PFS分别为16.1和14.3周;中位OS分别为14.7、16.2月;队列2:拉帕替尼组、联合组和帕唑帕尼组的ORR分别为47%、58%、31%;中位PFS分别为16.0、16.0、11.4周;≥ 3级不良事件发生率分别为17%、50%、46%
[1]
Siegel RL, Miller KD, Jemal A, et al. Cancer statistics, 2018[J]. CA Cancer J Clin201868(1):7-30.
[2]
Lim B, Woodward WA, Wang X, et al. Inflammatory breast cancer biology: the tumour microenvironment is key[J]. Nat Rev Cancer201818(8):485-499.
[3]
Saberi-Karimian M, Katsiki N, Caraglia M,et al. Vascular endothelial growth factor: An important molecular target of curcumin[J]. Crit Rev Food Sci Nutr, 201959(2):299-312.
[4]
Fouad TM, Barrera AMG, Reuben JM, et al. Inflammatory breast cancer: a proposed conceptual shift in the UICC-AJCC TNM staging system[J]. Lancet Oncol201718(4):e228-e232.
[5]
Masuda H, Brewer TM, Liu DD, et al. Long-term treatment efficacy in primary inflammatory breast cancer by hormonal receptor- and HER2-defined subtypes [J]. Ann Oncol, 201425(2):384-391.
[6]
Kupstas AR, Hoskin TL, Day CN, et al. Biological subtype, treatment response and outcomes in inflammatory breast cancer using data from the National Cancer Database[J]. Br J Surg2020, 107(8):1033-1041.
[7]
Costa R, Santa-Maria CA, Rossi G, et al. Developmental therapeutics for inflammatory breast cancer: Biology and translational directions[J]. Oncotarget20178(7):12 417-12 432.
[8]
Schlichting JA, Soliman AS, Schairer C, et al. Inflammatory and non-inflammatory breast cancer survival by socioeconomic position in the Surveillance, Epidemiology, and End Results database, 1990-2008[J]. Breast Cancer Res Treat2012134(3):1257-1268.
[9]
Das A, Mahapatra S, Bandyopadhyay D, et al. Bleeding with vascular endothelial growth factor tyrosine kinase inhibitor: A network meta-analysis[J]. Crit Rev Oncol Hematol2021157:103 186.
[10]
Bose D, Banerjee S, Singh RK, et al. Vascular endothelial growth factor encoded by Parapoxviruses can regulate metabolism and survival of triple negative breast cancer cells[J]. Cell Death Dis2020, 11(11):996.
[11]
Aalders KC, Tryfonidis K, Senkus E, et al. Anti-angiogenic treatment in breast cancer: facts, successes, failures and future perspectives[J]. Cancer Treat Rev, 201753:98-110.
[12]
Deryugina EI, Quigley JP. Tumor angiogenesis: MMP-mediated induction of intravasation and metastasis sustaining neo-vasculature[J]. Matrix Biol201544-46:94-112.
[13]
Koutras A, Kotoula V, Fountzilas G, et al. Prognostic and predictive role of vascular endothelial growth factor polymorphisms in breast cancer[J]. Pharmacogenomics201516(1):79-94.
[14]
Apte RS, Chen DS, Ferrara N. VEGF insignaling and disease: beyond discovery and development[J]. Cell, 2019176(6):1248-1264.
[15]
Coelho AL, Gomes MP, Catarino RJ, et al. Angiogenesis in NSCLC: is vessel co-option the trunk that sustains the branches? [J].Oncotarget20178(24):39 795-39 804.
[16]
Mohamed TK, Batran RZ, Elseginy SA, et al. Synthesis, anticancer effect and molecular modeling of new thiazolylpyrazolyl coumarin derivatives targeting VEGFR-2 kinase and inducing cell cycle arrest and apoptosis[J]. Bioorg Chem201985:253-273.
[17]
Madu CO, Wang S, Madu CO, et al. Angiogenesis inbreast cancer progression, diagnosis, and treatment[J]. J Cancer, 202011(15):4474-4494.
[18]
Linderholm BK, Lindh B, Beckman L,et al. Prognostic correlation of basic fibroblast growth factor and vascular endothelial growth factor in 1307 primary breast cancers[J]. Clin Breast Cancer, 2003, 4(5):340-347.
[19]
Adams J, Carder PJ, Downey S, et al. Vascular endothelial growth factor in breast cancer. Comparison of plasma, serum, and tissue VEGF and micro vessel density and effects of tamoxifen[J]. Cancer Res200060(11):2898-2905.
[20]
Foekens JA, Peters HA, Grebenchtchikov N, et al. High tumor levels of vascular endothelial growth factor predict poor response to systemic therapy in advanced breast cancer[J]. Cancer Res, 200161:5407-5414.
[21]
Van der Auwera I, Van Laere SJ, Van den Eynden GG, et al. Increased angiogenesis and lymphangiogenesis in inflammatory versus noninflammatory breast cancer by real-time reverse transcriptase-PCR gene expression quantification[J]. Clin Cancer Res, 200410(23):7965-7971.
[22]
Arias-Pulido H, Chaher N, Gong Y, et al. Tumor stromal vascular endothelial growth factor A is predictive of poor outcome in inflammatory breast cancer[J]. BMC Cancer201212:298.
[23]
Folkman J. Tumor angiogenesis: therapeutic implications [J]. N Engl J Med1971285:1182-1186.
[24]
Lugano R, Ramachandran M, Dimberg A. Tumor angiogenesis: causes, consequences, challenges and opportunities[J]. Cell Mol Life Sci202077(9):1745-1770.
[25]
Garcia J, Hurwitz HI, Sandler AB,et al. Bevacizumab (Avastin®) in cancer treatment: A review of 15 years of clinical experience and future outlook[J]. Cancer Treat Rev, 202086:102 017.
[26]
Hey SP, Gyawali B, D’Andrea E,et al. A systematic review and meta-analysis of bevacizumab in first-line metastatic breast cancer:lessons for research and regulatory enterprises[J]. J Natl Cancer Inst, 2020112(4):335-342.
[27]
Li Q, Wang Y, Jia W, et al. Low-dose anti-angiogenic therapy sensitizes breast cancer to PD-1 blockade[J]. Clin Cancer Res202026(7):1712-1724.
[28]
Miller K, Wang M, Gralow J, et al. Paclitaxel plus bevacizumab versus paclitaxel alone for metastatic breast cancer[J]. N Engl J Med2007357(26):2666-2676.
[29]
Robert NJ, Diéras V, Glaspy J, et al. RIBBON-1: randomized, double-blind, placebo-controlled, phase Ⅲ trial of chemotherapy with or without bevacizumab for first-line treatment of human epidermal growth factor receptor 2-negative, locally recurrent or metastatic breast cancer[J]. J Clin Oncol, 201129(10):1252-1260.
[30]
Brufsky AM, Hurvitz S, Perez E, et al. RIBBON-2: a randomized, double-blind, placebo-controlled, phase Ⅲ trial evaluating the efficacy and safety of bevacizumab in combination with chemotherapy for second-line treatment of human epidermal growth factor receptor 2-negative metastatic breast cancer[J]. J Clin Oncol201129(32):4286-4293.
[31]
Miles D, Cameron D, Bondarenko I, et al. Bevacizumab plus paclitaxel versus placebo plus paclitaxel as first-line therapy for HER2-negative metastatic breast cancer (MERiDiAN): A double-blind placebo-controlled randomised phase Ⅲ trial with prospective biomarker evaluation[J]. Eur J Cancer201770:146-155.
[32]
Dickler MN, Barry WT, Cirrincione CT, et al. Phase Ⅲ trial evaluating letrozole as first-line endocrine therapy with or without bevacizumab for the treatment of postmenopausal women with hormone receptor-positive advanced-stage breast cancer: CALGB 40503 (Alliance)[J]. J Clin Oncol201634(22):2602-2609.
[33]
Gligorov J, Doval D, Bines J, et al. Maintenance capecitabine and bevacizumab versus bevacizumab alone after initial first-line bevacizumab and docetaxel for patients with HER2-negative metastatic breast cancer (IMELDA): a randomized, open-label, phase 3 trial[J]. Lancet Oncol201415(12):1351-1360.
[34]
Spalding BJ. Thumbs up for avastin[J]. Nat Biotechnol200826(4):365.
[35]
Wedam SB, Low JA, Yang SX, et al. Antiangiogenic and antitumor effects of bevacizumab in patients with inflammatory and locally advanced breast cancer[J]. J Clin Oncol200624(5):769-777.
[36]
Bertucci F, Fekih M, Autret A, et al. Bevacizumab plus neoadjuvant chemotherapy in patients with HER2-negative inflammatory breast cancer (BEVERLY-1): a multicentre, single-arm, phase 2 study[J]. Lancet Oncol201617:600-611.
[37]
Pierga JY, Petit T, Delozier T, et al. Neoadjuvant bevacizumab, trastuzumab, and chemotherapy for primary inflammatory HER2-positive breast cancer (BEVERLY-2): an open-label, single-arm phase 2 study[J]. Lancet Oncol201213:375-384.
[38]
Pierga JY, Petit T, Levy C, et al. Pathological response and circulating tumor cell count identifies treated HER2t inflammatory breast cancer patients with excellent prognosis: BEVERLY-2 survival data[J]. Clin Cancer Res201521(6):1298-1304.
[39]
Nahleh ZA, Barlow WE, Hayes DF, et al. SWOG S0800 (NCI CDR0000636131): addition of bevacizumab to neoadjuvant nab-paclitaxel with dose-dense doxorubicin and cyclophosphamide improves pathologic complete response (pCR) rates in inflammatory or locally advanced breast cancer[J]. Breast Cancer Res Treat2016158:485-495.
[40]
Palazzo A, Dellapasqua S, Munzone E, et al. Phase Ⅱ trial of bevacizumab plus weekly paclitaxel, carboplatin, and metronomic cyclophosphamide with or without trastuzumab and endocrine therapy as preoperative treatment of inflammatory breast cancer[J]. Clin Breast Cancer201818(4):328-335.
[41]
Lenzer J. FDA committee votes to withdraw bevacizumab for breast cancer[J]. BMJ, 2011, 343:d4244.
[42]
Tabouret E, Bertucci F, Pierga JY, et al. MMP2 and MMP9 serum levels are associated with favorable outcome in patients with inflammatory breast cancer treated with bevacizumab-based neoadjuvant chemotherapy in the BEVERLY-2 study[J]. Oncotarget20167(14):18 531-18 540.
[43]
Pierga JY, Bidard FC, Autret A, et al. Circulating tumour cells and pathological complete response: independent prognostic factors in inflammatory breast cancer in a pooled analysis of two multicentre phase Ⅱ trials (BEVERLY-1 and -2) of neoadjuvant chemotherapy combined with bevacizumab[J]. Ann Oncol201728:103-109.
[44]
Overmoyer B, Fu P, Hoppel C, et al. Inflammatorybreast cancer as a model disease to study tumor angiogenesis: Results of a phase IB trial of combination SU5416 and doxorubicin[J]. Clin Cancer Res200713(19):5862-5868.
[45]
Cristofanilli M, Johnston SR, Manikhas A,et al. A randomized phase Ⅱ study of lapatinib + pazopanib versus lapatinib in patients with HER2+ inflammatory breast cancer[J]. Breast Cancer Res Treat2013137(2):471-482.
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