三阴性乳腺癌靶向治疗进展

董国雷; 赵伟鹏; 佟仲生

doi:10.3969/j.issn.1000-8179.2019.12.479

三阴性乳腺癌靶向治疗进展

doi: 10.3969/j.issn.1000-8179.2019.12.479

天津医科大学肿瘤医院乳腺肿瘤内科，国家肿瘤临床医学研究中心，天津市肿瘤防治重点实验室，天津市恶性肿瘤临床医学研究中心，乳腺癌防治教育部重点实验室（天津市300060）

详细信息

作者简介:
董国雷专业方向为乳腺癌诊断，内科治疗，基础及临床转化研究等。E-mail：nkdongguolei@163.com

通讯作者:
佟仲生 tongzhongshengtj@163.com

计量
- 文章访问数: 96
- HTML全文浏览量: 17
- PDF下载量: 15
- 被引次数: 0
出版历程
- 收稿日期: 2019-04-29
- 修回日期: 2019-06-17
- 刊出日期: 2019-06-30

Advances in targeted therapy for triple-negative breast cancer

Department of Breast Oncology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center of Cancer, Tianjin Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Key Laboratory of Breast Cancer Prevention and Therapy, Tianjin Medical University (Ministry of Education) Tianjin 300060, China

More Information

Corresponding author: Zhongsheng Tong; E-mail: tongzhongshengtj@163.com

摘要

摘要: 三阴性乳腺癌（triple-negative breast cancer，TNBC）是雌、孕激素受体和HER-2表达均为阴性的乳腺癌，侵袭性强，与其他分子分型乳腺癌相比复发率较高，生存率低。临床上内科治疗主要以化疗为主，随着对TNBC分子分型的深入探索，靶向治疗的研究逐渐成为关注的焦点。近些年，多种靶向药物进入临床试验，取得一定疗效，不良反应相对较轻，部分药物已批准上市。本文将对TNBC的靶向治疗应用进展进行综述。
- 三阴性乳腺癌 /
- 靶向治疗 /
- PARP /
- Trop-2 /
- 免疫检查点 /
- 雄激素 /
- 抗血管生成
Abstract: Triple negative breast cancer (TNBC) is a highly aggressive subtype of breast cancer that is characterized by the lack of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER-2), thereby making it difficult to treat. Owing to the aggressive clinical behavior of TNBC and the lack of recognized molecular targets for therapy, patients with TNBC have shown poorer outcomes than those with other subtypes of breast cancer. Chemotherapy is the primary established systemic treatment for TNBC. However, various novel therapeutic targets have come into focus with the advances in molecular characterization of TNBC. In recent years, several targeted drugs have undergone clinical trials and have shown certain curative effects with relatively mild adverse reactions. The Food and Drug Administration has approved some of these drugs. In the current review, we have summarized the advances in the targeted therapy of TNBC.
- triple-negative breast cancer /
- targeted therapy /
- poly ADP-ribose polymerase (PARP) /
- Trop-2 /
- immune checkpoints /
- androgen /
- anti-angiogenic

HTML全文

参考文献(30)

[1]	Lin NU, Vanderplas A, Hughes ME, et al. Clinicopathologic features, patterns of recurrence, and survival among women with triple-negative breast cancer in the National Comprehensive Cancer Network [J]. Cancer, 2012, 118(22):5463-5472. doi: 10.1002/cncr.27581
[2]	Bianchini G, Balko JM, Mayer IA, et al. Triple-negative breast cancer: challenges and opportunities of a heterogenous disease[J]. Nat Rev Clin Oncol, 2016, 13(11):674-690. doi: 10.1038/nrclinonc.2016.66
[3]	Venkitaraman AR. Linking the cellular functions of BRCA genes to cancer pathogenesis and treatment[J]. Annu Rev Pathol, 2009, 4: 461-487. doi: 10.1146/annurev.pathol.3.121806.151422
[4]	Cancer Genome Atlas Network. Comprehensive molecular portraits of human breast tumours[J]. Nature, 2012, 490(7418):61-70. doi: 10.1038/nature11412
[5]	Audebert M, Salles B, Calsou P. Involvement of poly(ADP-ribose) polymerase-1 and XRCC1/DNA ligase Ⅲ in an alternative route for DNA double-strand breaks rejoining[J]. J Biol Chem, 2004, 279(53): 55117-55126. doi: 10.1074/jbc.M404524200
[6]	Robson M, Im SA, Senkus E, et al. Olaparib for metastatic breast cancer in patients with a germline BRCA mutation[J]. N Engl J Med, 2017, 377 (6):523-533. doi: 10.1056/NEJMoa1706450
[7]	Robson ME, Tung N, Conte P, et al. Olympi AD final overall survival and tolerability results: olaparib versus chemotherapy treatment of physician's choice in patients with a germline BRCA mutation and HER- 2 negative metastatic breast cancer[J]. Ann Oncol, 2019, 30(4):558- 566. doi: 10.1093/annonc/mdz012
[8]	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. doi: 10.1056/NEJMoa1802905
[9]	Ettl J, Quek RGW, Lee KH, et al. Quality of life with talazoparib versus physician's choice of chemotherapy in patients with advanced breast cancer and germline BRCA1/2 mutation: patient-reported outcomes from the EMBRACA phase Ⅲ trial[J]. Ann Oncol, 2018, 29(9):1939- 1947. doi: 10.1093/annonc/mdy257
[10]	Shvartsur A, Bonavida B. Trop2 and its overexpression in cancer: regulation and clinical/therapeutic implications[J].Genes Cancer, 2015, 6(3-4):84-105. https://www.ncbi.nlm.nih.gov/pubmed/26000093
[11]	Goldenberg DM, Stein R, Sharkey RM. The emergence of trophoblast cell-surface antigen 2 (TROP-2) as a novel cancer target[J]. Oncotarget, 2018, 9(48):28989-29006. http://europepmc.org/articles/PMC6034748/
[12]	Ambrogi F, Fornili M, Broacchi P, et al. Trop-2 is a determinant of breast cancer survival[J]. PLoS One, 2014, 9(5):e96993. doi: 10.1371/journal.pone.0096993
[13]	Ocean AJ, Starodub AN, Bardia A, et al. Sacituzumabgovitecan (IMMU- 132), an anti-Trop-2-SN-38 antibody-drug conjugate for the treatment of diverse epithelial cancers: safety and pharmacokinetics[J]. Cancer, 2017, 123(19):3843-3854. doi: 10.1002/cncr.30789
[14]	Bardia A, Mayer IA, Diamond JR, et al. Efficacy and safety of anti-Trop- 2 antibody drug conjugate sacituzumabgovitecan (IMMU- 132) in heavily pretreated patients with metastatic triple- negative breast cancer[J]. J Clin Oncol, 2017, 35(19):2141-2148. doi: 10.1200/JCO.2016.70.8297
[15]	Li B, Chan HL, Chen P. Immune checkpoint inhibitors: basics and challenges[J]. Curr Med Chem, 2017, 24:1-15. http://d.old.wanfangdata.com.cn/Periodical/zgzllc-e201404002
[16]	Sabatier R, Finetti P, Mamessier E, et al. Prognostic and predictive value of PDL1 expression in breast cancer[J]. Oncotarget, 2015, 6(7):5449- 5464. http://www.wanfangdata.com.cn/details/detail.do?_type=perio&id=10.1080/15384047.2019.1583533
[17]	Herbst RS, Soria JC, Kowanetz M, et al. Predictive correlates of response to the anti-PD-L1 antibody MPDL3280A in cancer patients[J]. Nature, 2014, 515(7528):563-567. doi: 10.1038/nature14011
[18]	Swoboda A, Nanda R. Immune checkpoint blockade for breast cancer [J]. Cancer Treat Res, 2018, 173:155-165. http://d.old.wanfangdata.com.cn/OAPaper/oai_pubmedcentral.nih.gov_3587160
[19]	Schmid P, Adams S, Rugo HS, et al. Atezolizumab and nab-paclitaxel in advanced triple-negative breast cancer[J]. N Engl J Med, 2018, 379(22): 2108-2121. doi: 10.1056/NEJMoa1809615
[20]	Gerratana L, Basile D, Buono G, et al. Androgen receptor in triple negative breast cancer: a potential target for the targetless subtype[J]. Cancer Treat Rev, 2018, 68:102-110. doi: 10.1016/j.ctrv.2018.06.005
[21]	Lehmann BD, Bauer JA, Chen X, et al. Identification of human triplenegative breast cancer subtypes and preclinical models for selection of targeted therapies[J]. J Clin Invest, 2011, 121(7):2750-2767. doi: 10.1172/JCI45014
[22]	Gucalp A, Tolaney S, Isakoff SJ, et al. Phase Ⅱ trial of bicalutamide in patients with androgen receptor-positive, estrogen receptor-negative metastatic breast cancer[J]. Clin Cancer Res, 2013, 19(19):5505-5512. doi: 10.1158/1078-0432.CCR-12-3327
[23]	Traina TA, Miller K, Yardley DA, et al. Enzalutamide for the treatment of androgen receptor-expressing triple-negative breast cancer[J]. J Clin Oncol, 2018, 36(9):884-890. doi: 10.1200/JCO.2016.71.3495
[24]	Linderholm BK, Hellborg H, Johansson U, et al. Significantly higher levels of vascular endothelial growth factor (VEGF) and shorter survival times for patients with primary operable triple-negative breast cancer [J]. Ann Oncol, 2009, 20(10):1639-1646. doi: 10.1093/annonc/mdp062
[25]	Miller K, Wang M, Gralow J, et al. Paclitaxel plus bevacizumab versus paclitaxel alone for metastatic breast cancer[J]. N Engl J Med, 2007, 357(26):2666-2676. doi: 10.1056/NEJMoa072113
[26]	Miles DW, Chan A, Dirix LY, et al. Phase Ⅲ study of bevacizumab plus docetaxel compared with placebo plus docetaxel for the first- line treatment of human epidermal growth factor receptor 2-negative metastatic breast cancer[J]. J Clin Oncol, 2010, 28(20):3239-3247. doi: 10.1200/JCO.2008.21.6457
[27]	Robert NJ, Diéras V, Glaspy J, et al. RIBBON-1: randomized, doubleblind, 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, 2011, 29(10):1252-1260. doi: 10.1200/JCO.2010.28.0982
[28]	Miles DW, Diéras V, Cortés J, et al. First-line bevacizumab in combination with chemotherapy for HER- 2 negative metastatic breast cancer: pooled and subgroup analyses of data from 2447 patients[J]. Ann Oncol, 2013, 24(11):2773-2780. doi: 10.1093/annonc/mdt276
[29]	Bell R, Brown J, Parmar M, et al. Final efficacy and updated safety results of the randomized phase Ⅲ BEATRICE trial evaluating adjuvant bevacizumab-containing therapy in triple-negative early breast cancer [J]. Ann Oncol, 2017, 28(4):754-760. https://www.ncbi.nlm.nih.gov/pubmed/27993816
[30]	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), 2018, 97(36):e12222. doi: 10.1097/MD.0000000000012222