Login Register Cart 0
Generic placeholder image

当代肿瘤药物靶点

Editor-in-Chief

ISSN (Print): 1568-0096
ISSN (Online): 1873-5576

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe Translate in English
Case Report

接受奥拉帕尼单药治疗的转移性三阴性乳腺癌患者的持久无病生存期

卷 22, 期 6, 2022

发表于: 27 April, 2022

页: [530 - 536] 页: 7

弟呕挨: 10.2174/1568009622666220214092207

open access plus

摘要

背景:转移性三阴性乳腺癌（mTNBC）预后差，有效的靶向治疗方案较少。奥拉帕尼（Olaparib）是一种多聚（ADP-ribose）聚合酶（PARP）抑制剂，已被FDA加速批准用于有害的BRCA突变的人表皮生长因子受体2 （HER2）阴性的晚期/转移性乳腺癌患者。然而，很少有数据表明具有特殊形式的生殖细胞和/或体细胞BRCA1/2的患者（如大片段变异）可以受益于PARP抑制剂。 病例描述:2011年，一名40岁的女性被诊断为TNBC，右侧乳房pT2N0M0，约3年后左侧乳房出现一个新的不规则小结节，也被诊断为TNBC。2017年，计算机断层扫描（CT）显示TNBC转移到肺和大脑。对一例肺转移标本进行下一代测序（NGS），结果显示同源重组缺陷（HRD）评分为67分，BRCA1外显子2的种系大量缺失，BRCA2-STARD13的体细胞重排和RAD51拷贝数丢失。自2017年9月起，患者接受奥拉帕尼治疗。直到病例报告之日，患者接受定期随访，无复发。 结论:据我们所知，这是第一个描述肺和脑转移性TNBC合并生殖细胞和体细胞大重排和高HRD评分的患者，该患者从奥拉帕尼单药治疗中获得了长期受益。在临床上应用NGS治疗TNBC具有广阔的前景。

关键词: BRCA1/2重排，HRD阳性，转移性三阴性乳腺癌，PARP抑制剂，奥拉帕尼，长期无病生存。

« Previous
图形摘要

[1]
Stover, D.G.; Parsons, H.A.; Ha, G.; Freeman, S.S.; Barry, W.T.; Guo, H.; Choudhury, A.D.; Gydush, G.; Reed, S.C.; Rhoades, J.; Rotem, D.; Hughes, M.E.; Dillon, D.A.; Partridge, A.H.; Wagle, N.; Krop, I.E.; Getz, G.; Golub, T.R.; Love, J.C.; Winer, E.P.; Tolaney, S.M.; Lin, N.U.; Adalsteinsson, V.A. Association of cell-free DNA tumor fraction and somatic copy number alterations with survival in metastatic triple-negative breast cancer. J. Clin. Oncol., 2018, 36(6), 543-553.
[http://dx.doi.org/10.1200/JCO.2017.76.0033] [PMID: 29298117]
[2]
Kumar, P.; Mukherjee, M.; Johnson, J.P.S.; Patel, M.; Huey, B.; Albertson, D.G.; Simin, K. Cooperativity of Rb, Brca1, and p53 in malignant breast cancer evolution. PLoS Genet., 2012, 8(11)e1003027
[http://dx.doi.org/10.1371/journal.pgen.1003027] [PMID: 23173005]
[3]
Belli, C.; Duso, B.A.; Ferraro, E.; Curigliano, G. Homologous recombination deficiency in triple negative breast cancer. Breast, 2019, 45, 15-21.
[http://dx.doi.org/10.1016/j.breast.2019.02.007] [PMID: 30818144]
[4]
Morante, Z.; De la Cruz Ku, G.A.; Enriquez, D.; Saavedra, A.; Luján, M.; Luque, R.; Eyzaguirre, E.; Guardamino, D.; Valcárcel, B.; Araujo, J.M.; Pinto, J.; Fuentes, H.A.; Neciosup, S.P.; Gomez, H.L. Post-recurrence survival in triple negative breast cancer. J. Clin. Oncol., 2018, 36(15)(Suppl.), e13120-e13120.
[http://dx.doi.org/10.1200/JCO.2018.36.15_suppl.e13120]
[5]
Dawood, S.; Broglio, K.; Esteva, F.J.; Yang, W.; Kau, S-W.; Islam, R.; Albarracin, C.; Yu, T.K.; Green, M.; Hortobagyi, G.N.; Gonzalez-Angulo, A.M. Survival among women with triple receptor-negative breast cancer and brain metastases. Ann. Oncol., 2009, 20(4), 621-627.
[http://dx.doi.org/10.1093/annonc/mdn682] [PMID: 19150943]
[6]
Sharma, P.; Klemp, J.R.; Kimler, B.F.; Mahnken, J.D.; Geier, L.J.; Khan, Q.J.; Elia, M.; Connor, C.S.; McGinness, M.K.; Mammen, J.M.; Wagner, J.L.; Ward, C.; Ranallo, L.; Knight, C.J.; Stecklein, S.R.; Jensen, R.A.; Fabian, C.J.; Godwin, A.K. Germline BRCA mutation evaluation in a prospective triple-negative breast cancer registry: implications for hereditary breast and/or ovarian cancer syndrome testing. Breast Cancer Res. Treat., 2014, 145(3), 707-714.
[http://dx.doi.org/10.1007/s10549-014-2980-0] [PMID: 24807107]
[7]
Fong, P.C.; Boss, D.S.; Yap, T.A.; Tutt, A.; Wu, P.; Mergui-Roelvink, M.; Mortimer, P.; Swaisland, H.; Lau, A.; O’Connor, M.J.; Ashworth, A.; Carmichael, J.; Kaye, S.B.; Schellens, J.H.; de Bono, J.S. Inhibition of poly(ADP-ribose) polymerase in tumors from BRCA mutation carriers. N. Engl. J. Med., 2009, 361(2), 123-134.
[http://dx.doi.org/10.1056/NEJMoa0900212] [PMID: 19553641]
[8]
Robson, M.; Im, S.A.; Senkus, E.; Xu, B.; Domchek, S.M.; Masuda, N.; Delaloge, S.; Li, W.; Tung, N.; Armstrong, A.; Wu, W.; Goessl, C.; Runswick, S.; Conte, P. Olaparib for metastatic breast cancer in patients with a germline BRCA mutation. N. Engl. J. Med., 2017, 377(6), 523-533.
[http://dx.doi.org/10.1056/NEJMoa1706450] [PMID: 28578601]
[9]
Mirza, M.R.; Monk, B.J.; Herrstedt, J.; Oza, A.M.; Mahner, S.; Redondo, A.; Fabbro, M.; Ledermann, J.A.; Lorusso, D.; Vergote, I.; Ben-Baruch, N.E.; Marth, C. Mαdry, R.; Christensen, R.D.; Berek, J.S.; Dørum, A.; Tinker, A.V.; du Bois, A.; González-Martín, A.; Follana, P.; Benigno, B.; Rosenberg, P.; Gilbert, L.; Rimel, B.J.; Buscema, J.; Balser, J.P.; Agarwal, S.; Matulonis, U.A. Niraparib maintenance therapy in platinum-sensitive, recurrent ovarian cancer. N. Engl. J. Med., 2016, 375(22), 2154-2164.
[http://dx.doi.org/10.1056/NEJMoa1611310] [PMID: 27717299]
[10]
Swisher, E.M.; Lin, K.K.; Oza, A.M.; Scott, C.L.; Giordano, H.; Sun, J.; Konecny, G.E.; Coleman, R.L.; Tinker, A.V.; O’Malley, D.M.; Kristeleit, R.S.; Ma, L.; Bell-McGuinn, K.M.; Brenton, J.D.; Cragun, J.M.; Oaknin, A.; Ray-Coquard, I.; Harrell, M.I.; Mann, E.; Kaufmann, S.H.; Floquet, A.; Leary, A.; Harding, T.C.; Goble, S.; Maloney, L.; Isaacson, J.; Allen, A.R.; Rolfe, L.; Yelensky, R.; Raponi, M.; McNeish, I.A. Rucaparib in relapsed, platinum-sensitive high-grade ovarian carcinoma (ARIEL2 Part 1): an international, multicentre, open-label, phase 2 trial. Lancet Oncol., 2017, 18(1), 75-87.
[http://dx.doi.org/10.1016/S1470-2045(16)30559-9] [PMID: 27908594]
[11]
Pantelidou, C.; Sonzogni, O.; De Oliveria Taveira, M.; Mehta, A.K.; Kothari, A.; Wang, D.; Visal, T.; Li, M.K.; Pinto, J.; Castrillon, J.A.; Cheney, E.M.; Bouwman, P.; Jonkers, J.; Rottenberg, S.; Guerriero, J.L.; Wulf, G.M.; Shapiro, G.I. PARP inhibitor efficacy depends on CD8+ T-cell recruitment via intratumoral STING pathway activation in BRCA-deficient models of triple-negative breast cancer. Cancer Discov., 2019, 9(6), 722-737.
[http://dx.doi.org/10.1158/2159-8290.CD-18-1218] [PMID: 31015319]
[12]
Reisländer, T.; Lombardi, E.P.; Groelly, F.J.; Miar, A.; Porru, M.; Di Vito, S.; Wright, B.; Lockstone, H.; Biroccio, A.; Harris, A.; Londoño-Vallejo, A.; Tarsounas, M. BRCA2 abrogation triggers innate immune responses potentiated by treatment with PARP inhibitors. Nat. Commun., 2019, 10(1), 3143.
[http://dx.doi.org/10.1038/s41467-019-11048-5] [PMID: 31316060]
[13]
Chopra, N.; Tovey, H.; Pearson, A.; Cutts, R.; Toms, C.; Proszek, P.; Hubank, M.; Dowsett, M.; Dodson, A.; Daley, F.; Kriplani, D.; Gevensleben, H.; Davies, H.R.; Degasperi, A.; Roylance, R.; Chan, S.; Tutt, A.; Skene, A.; Evans, A.; Bliss, J.M.; Nik-Zainal, S.; Turner, N.C. Homologous recombination DNA repair deficiency and PARP inhibition activity in primary triple negative breast cancer. Nat. Commun., 2020, 11(1), 2662.
[http://dx.doi.org/10.1038/s41467-020-16142-7] [PMID: 32471999]
[14]
Gatti, M.; Imhof, R.; Huang, Q.; Baudis, M.; Altmeyer, M. The ubiquitin ligase TRIP12 limits PARP1 trapping and constrains PARP inhibitor efficiency. Cell Rep., 2020, 32(5)107985
[http://dx.doi.org/10.1016/j.celrep.2020.107985] [PMID: 32755579]
[15]
Lafontaine, J.; Boisvert, J-S.; Glory, A.; Coulombe, S.; Wong, P. Synergy between non-thermal plasma with radiation therapy and olaparib in a panel of breast cancer cell lines. Cancers (Basel), 2020, 12(2)E348
[http://dx.doi.org/10.3390/cancers12020348] [PMID: 32033118]
[16]
Livraghi, L.; Garber, J.E. PARP inhibitors in the management of breast cancer: current data and future prospects. BMC Med., 2015, 13(1), 188.
[http://dx.doi.org/10.1186/s12916-015-0425-1] [PMID: 26268938]
[17]
Nedeljković M.; Damjanović A. Mechanisms of chemotherapy resistance in triple-negative breast cancer-how we can rise to the challenge. Cells, 2019, 8(9)E957
[http://dx.doi.org/10.3390/cells8090957] [PMID: 31443516]
[18]
Moore, K.; Colombo, N.; Scambia, G.; Kim, B-G.; Oaknin, A.; Friedlander, M.; Lisyanskaya, A.; Floquet, A.; Leary, A.; Sonke, G.S.; Gourley, C.; Banerjee, S.; Oza, A.; González-Martín, A.; Aghajanian, C.; Bradley, W.; Mathews, C.; Liu, J.; Lowe, E.S.; Bloomfield, R.; DiSilvestro, P. Maintenance olaparib in patients with newly diagnosed advanced ovarian cancer. N. Engl. J. Med., 2018, 379(26), 2495-2505.
[http://dx.doi.org/10.1056/NEJMoa1810858] [PMID: 30345884]
[19]
González-Martín, A.; Pothuri, B.; Vergote, I.; DePont Christensen, R.; Graybill, W.; Mirza, M.R.; McCormick, C.; Lorusso, D.; Hoskins, P.; Freyer, G.; Baumann, K.; Jardon, K.; Redondo, A.; Moore, R.G.; Vulsteke, C.; O’Cearbhaill, R.E.; Lund, B.; Backes, F.; Barretina-Ginesta, P.; Haggerty, A.F.; Rubio-Pérez, M.J.; Shahin, M.S.; Mangili, G.; Bradley, W.H.; Bruchim, I.; Sun, K.; Malinowska, I.A.; Li, Y.; Gupta, D.; Monk, B.J. Niraparib in patients with newly diagnosed advanced ovarian cancer. N. Engl. J. Med., 2019, 381(25), 2391-2402.
[http://dx.doi.org/10.1056/NEJMoa1910962] [PMID: 31562799]
[20]
Sharma, P.; Barlow, W.E.; Godwin, A.K.; Pathak, H.; Isakova, K.; Williams, D.; Timms, K.M.; Hartman, A.R.; Wenstrup, R.J.; Linden, H.M.; Tripathy, D.; Hortobagyi, G.N.; Hayes, D.F. Impact of homologous recombination deficiency biomarkers on outcomes in patients with triple-negative breast cancer treated with adjuvant doxorubicin and cyclophosphamide (SWOG S9313). Ann. Oncol., 2018, 29(3), 654-660.
[http://dx.doi.org/10.1093/annonc/mdx821] [PMID: 29293876]
[21]
Huang, K.; Wang, J.; Yang, B.; Bai, Y.; Zhao, X. 1206P Computing HRD score by a capture-based NGS panel reveal its prevalence in Chinese breast, ovarian, prostate and pancreatic cancer patients. Ann. Oncol., 2020, 31, S790.
[http://dx.doi.org/10.1016/j.annonc.2020.08.100]

Rights & Permissions Print Cite
Article Metrics
30
1
© 2024 Bentham Science Publishers | Privacy Policy