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Current Cancer Drug Targets


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

Case Report

Durable Disease-free Survival in a Patient with Metastatic Triple-negative Breast Cancer Treated with Olaparib Monotherapy

Author(s): Xue Wang, Nanlin Hu, Lina Cui, Yiran Si, Jian Yue, Fangchao Zheng, Yikun Kang and Peng Yuan*

Volume 22, Issue 6, 2022

Published on: 27 April, 2022

Page: [530 - 536] Pages: 7

DOI: 10.2174/1568009622666220214092207

open access plus


Background: Metastatic triple-negative breast cancer (mTNBC) has a poor prognosis and few effective targeted therapy options. Olaparib, a poly (ADP-ribose) polymerase (PARP) inhibitor, has been granted accelerated approval by FDA for patients with deleterious BRCA-mutated human epidermal growth factor receptor 2 (HER2)-negative advanced/metastatic breast cancer. However, there is little data demonstrating that patients with particular forms of germline and/or somatic BRCA1/2, such as large fragment variation, can benefit from PARP inhibitors.

Case Presentation: In 2011, a 40-year-old woman was diagnosed with TNBC having pT2N0M0 in the right breast, and a new irregular lesser tubercle in the left breast appeared after approximately 3 years, which was also diagnosed as TNBC. In 2017, computed tomography (CT) showed TNBC metastases to the lung and brain. A next-generation sequencing (NGS) was performed with a lung metastasis sample, and results showed a homologous recombination deficiency (HRD) score of 67, a germline large deletion of exon 2 in BRCA1, a novel somatic BRCA2-STARD13 rearrangement and copy number loss of RAD51. Since September 2017, the patient was treated with olaparib. Till the report date of this case, the patient underwent regular follow-up without disease recurrence.

Conclusion: To our knowledge, this is the first case describing a patient with lung- and brainmetastatic TNBC with combined germline and somatic large rearrangement and a high HRD score who achieved a long-term benefit from olaparib monotherapy. The use of NGS is promising in the treatment of TNBC in clinical practice.

Keywords: BRCA1/2 rearrangement, HRD positive, metastatic triple-negative breast cancer, PARP inhibitor, olaparib, longterm disease-free survival.

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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.
[] [PMID: 29298117]
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
[] [PMID: 23173005]
Belli, C.; Duso, B.A.; Ferraro, E.; Curigliano, G. Homologous recombination deficiency in triple negative breast cancer. Breast, 2019, 45, 15-21.
[] [PMID: 30818144]
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.
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.
[] [PMID: 19150943]
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.
[] [PMID: 24807107]
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.
[] [PMID: 19553641]
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.
[] [PMID: 28578601]
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.
[] [PMID: 27717299]
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.
[] [PMID: 27908594]
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.
[] [PMID: 31015319]
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.
[] [PMID: 31316060]
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.
[] [PMID: 32471999]
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
[] [PMID: 32755579]
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
[] [PMID: 32033118]
Livraghi, L.; Garber, J.E. PARP inhibitors in the management of breast cancer: current data and future prospects. BMC Med., 2015, 13(1), 188.
[] [PMID: 26268938]
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
[] [PMID: 31443516]
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.
[] [PMID: 30345884]
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.
[] [PMID: 31562799]
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.
[] [PMID: 29293876]
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.

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