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Published in: BMC Medicine 1/2015

Open Access 01-12-2015 | Review

PARP inhibitors in the management of breast cancer: current data and future prospects

Authors: Luca Livraghi, Judy E. Garber

Published in: BMC Medicine | Issue 1/2015

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Abstract

Poly(ADP-ribose) polymerases (PARP) are enzymes involved in DNA-damage repair. Inhibition of PARPs is a promising strategy for targeting cancers with defective DNA-damage repair, including BRCA1 and BRCA2 mutation-associated breast and ovarian cancers. Several PARP inhibitors are currently in trials in the adjuvant, neoadjuvant, and metastatic settings for the treatment of ovarian, BRCA-mutated breast, and other cancers. We herein review the development of PARP inhibitors and the basis for the excitement surrounding these agents, their use as single agents and in combinations, as well as their toxicities, mechanisms of acquired resistance, and companion diagnostics.
Literature
2.
go back to reference Mavaddat N, Barrowdale D, Andrulis IL, Domchek SM, Eccles D, Nevanlinna H, et al. Pathology of breast and ovarian cancers among BRCA1 and BRCA2 mutation carriers: results from the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). Cancer Epidemiol Biomarkers Prev. 2012;21:134–47. doi:10.1158/1055-9965.EPI-11-0775.PubMed Mavaddat N, Barrowdale D, Andrulis IL, Domchek SM, Eccles D, Nevanlinna H, et al. Pathology of breast and ovarian cancers among BRCA1 and BRCA2 mutation carriers: results from the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). Cancer Epidemiol Biomarkers Prev. 2012;21:134–47. doi:10.​1158/​1055-9965.​EPI-11-0775.PubMed
3.
go back to reference Sharma P, Klemp JR, Kimler BF, Mahnken JD, Geier LJ, Khan QJ, et al. 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;145:707–14. doi:10.1007/s10549-014-2980-0.PubMedPubMedCentral Sharma P, Klemp JR, Kimler BF, Mahnken JD, Geier LJ, Khan QJ, et al. 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;145:707–14. doi:10.​1007/​s10549-014-2980-0.PubMedPubMedCentral
4.
go back to reference Couch FJ, Hart SN, Sharma P, Toland AE, Wang X, Miron P, et al. Inherited mutations in 17 breast cancer susceptibility genes among a large triple-negative breast cancer cohort unselected for family history of breast cancer. J Clin Oncol. 2015;33:304–11. doi:10.1200/JCO.2014.57.1414.PubMed Couch FJ, Hart SN, Sharma P, Toland AE, Wang X, Miron P, et al. Inherited mutations in 17 breast cancer susceptibility genes among a large triple-negative breast cancer cohort unselected for family history of breast cancer. J Clin Oncol. 2015;33:304–11. doi:10.​1200/​JCO.​2014.​57.​1414.PubMed
5.
go back to reference Fong PC, Boss DS, Yap TA, Tutt A, Wu P, Mergui-Roelvink M, et al. Inhibition of poly(ADP-ribose) polymerase in tumors from BRCA mutation carriers. N Engl J Med. 2009;361:123–34. doi:10.1056/NEJMoa0900212.PubMed Fong PC, Boss DS, Yap TA, Tutt A, Wu P, Mergui-Roelvink M, et al. Inhibition of poly(ADP-ribose) polymerase in tumors from BRCA mutation carriers. N Engl J Med. 2009;361:123–34. doi:10.​1056/​NEJMoa0900212.PubMed
6.
go back to reference Kaufman B, Shapira-Frommer R, Schmutzler RK, Audeh MW, Friedlander M, Balmana J, et al. Olaparib monotherapy in patients with advanced cancer and a germline BRCA1/2 mutation. J Clin Oncol. 2015;33:244–50. doi:10.1200/JCO.2014.56.2728.PubMed Kaufman B, Shapira-Frommer R, Schmutzler RK, Audeh MW, Friedlander M, Balmana J, et al. Olaparib monotherapy in patients with advanced cancer and a germline BRCA1/2 mutation. J Clin Oncol. 2015;33:244–50. doi:10.​1200/​JCO.​2014.​56.​2728.PubMed
7.
go back to reference Gelmon KA, Tischkowitz M, Mackay H, Swenerton K, Robidoux A, Tonkin K, et al. Olaparib in patients with recurrent high-grade serous or poorly differentiated ovarian carcinoma or triple-negative breast cancer: a phase 2, multicentre, open-label, non-randomised study. Lancet Oncol. 2011;12:852–61. doi:10.1016/S1470-2045(11)70214-5.PubMed Gelmon KA, Tischkowitz M, Mackay H, Swenerton K, Robidoux A, Tonkin K, et al. Olaparib in patients with recurrent high-grade serous or poorly differentiated ovarian carcinoma or triple-negative breast cancer: a phase 2, multicentre, open-label, non-randomised study. Lancet Oncol. 2011;12:852–61. doi:10.​1016/​S1470-2045(11)70214-5.PubMed
12.
15.
go back to reference Bryant HE, Schultz N, Thomas HD, Parker KM, Flower D, Lopez E, et al. Specific killing of BRCA2-deficient tumours with inhibitors of poly(ADP-ribose) polymerase. Nature. 2005;434:913–7. doi:10.1038/nature03443.PubMed Bryant HE, Schultz N, Thomas HD, Parker KM, Flower D, Lopez E, et al. Specific killing of BRCA2-deficient tumours with inhibitors of poly(ADP-ribose) polymerase. Nature. 2005;434:913–7. doi:10.​1038/​nature03443.PubMed
16.
go back to reference Farmer H, McCabe N, Lord CJ, Tutt AN, Johnson DA, Richardson TB, et al. Targeting the DNA repair defect in BRCA mutant cells as a therapeutic strategy. Nature. 2005;434:917–21. doi:10.1038/nature03445.PubMed Farmer H, McCabe N, Lord CJ, Tutt AN, Johnson DA, Richardson TB, et al. Targeting the DNA repair defect in BRCA mutant cells as a therapeutic strategy. Nature. 2005;434:917–21. doi:10.​1038/​nature03445.PubMed
19.
go back to reference Tutt AN, Lord CJ, McCabe N, Farmer H, Turner N, Martin NM, et al. Exploiting the DNA repair defect in BRCA mutant cells in the design of new therapeutic strategies for cancer. Cold Spring Harb Symp Quant Biol. 2005;70:139–48. doi:10.1101/sqb.2005.70.012.PubMed Tutt AN, Lord CJ, McCabe N, Farmer H, Turner N, Martin NM, et al. Exploiting the DNA repair defect in BRCA mutant cells in the design of new therapeutic strategies for cancer. Cold Spring Harb Symp Quant Biol. 2005;70:139–48. doi:10.​1101/​sqb.​2005.​70.​012.PubMed
23.
go back to reference Balmana J, Tung NM, Isakoff SJ, Grana B, Ryan PD, Saura C, et al. Phase I trial of olaparib in combination with cisplatin for the treatment of patients with advanced breast, ovarian and other solid tumors. Ann Oncol. 2014;25:1656–63. doi:10.1093/annonc/mdu187.PubMed Balmana J, Tung NM, Isakoff SJ, Grana B, Ryan PD, Saura C, et al. Phase I trial of olaparib in combination with cisplatin for the treatment of patients with advanced breast, ovarian and other solid tumors. Ann Oncol. 2014;25:1656–63. doi:10.​1093/​annonc/​mdu187.PubMed
24.
25.
go back to reference O’Shaughnessy J, Schwartzberg L, Danso MA, Miller KD, Rugo HS, Neubauer M, et al. Phase III study of iniparib plus gemcitabine and carboplatin versus gemcitabine and carboplatin in patients with metastatic triple-negative breast cancer. J Clin Oncol. 2014;32:3840–7. doi:10.1200/JCO.2014.55.2984.PubMed O’Shaughnessy J, Schwartzberg L, Danso MA, Miller KD, Rugo HS, Neubauer M, et al. Phase III study of iniparib plus gemcitabine and carboplatin versus gemcitabine and carboplatin in patients with metastatic triple-negative breast cancer. J Clin Oncol. 2014;32:3840–7. doi:10.​1200/​JCO.​2014.​55.​2984.PubMed
27.
go back to reference Birgisdottir V, Stefansson OA, Bodvarsdottir SK, Hilmarsdottir H, Jonasson JG, Eyfjord JE. Epigenetic silencing and deletion of the BRCA1 gene in sporadic breast cancer. Breast Cancer Res. 2006;8:R38. doi:10.1186/bcr1522.PubMedPubMedCentral Birgisdottir V, Stefansson OA, Bodvarsdottir SK, Hilmarsdottir H, Jonasson JG, Eyfjord JE. Epigenetic silencing and deletion of the BRCA1 gene in sporadic breast cancer. Breast Cancer Res. 2006;8:R38. doi:10.​1186/​bcr1522.PubMedPubMedCentral
28.
go back to reference McCabe N, Turner NC, Lord CJ, Kluzek K, Bialkowska A, Swift S, et al. Deficiency in the repair of DNA damage by homologous recombination and sensitivity to poly(ADP-ribose) polymerase inhibition. Cancer Res. 2006;66:8109–15. doi:10.1158/0008-5472.CAN-06-0140.PubMed McCabe N, Turner NC, Lord CJ, Kluzek K, Bialkowska A, Swift S, et al. Deficiency in the repair of DNA damage by homologous recombination and sensitivity to poly(ADP-ribose) polymerase inhibition. Cancer Res. 2006;66:8109–15. doi:10.​1158/​0008-5472.​CAN-06-0140.PubMed
29.
go back to reference Lukas J, Lukas C, Bartek J. More than just a focus: the chromatin response to DNA damage and its role in genome integrity maintenance. Nat Cell Biol. 2011;13:1161–9. doi:10.1038/ncb2344.PubMed Lukas J, Lukas C, Bartek J. More than just a focus: the chromatin response to DNA damage and its role in genome integrity maintenance. Nat Cell Biol. 2011;13:1161–9. doi:10.​1038/​ncb2344.PubMed
30.
go back to reference Isakoff SJ, Overmoyer B, Tung NM, Gelman RS, Habin K, Qian J, et al. A phase II trial expansion cohort of the PARP inhibitor veliparib (ABT888) and temozolomide in BRCA1/2 associated metastatic breast cancer. Cancer Res. 2011;71:P3-16-05. Isakoff SJ, Overmoyer B, Tung NM, Gelman RS, Habin K, Qian J, et al. A phase II trial expansion cohort of the PARP inhibitor veliparib (ABT888) and temozolomide in BRCA1/2 associated metastatic breast cancer. Cancer Res. 2011;71:P3-16-05.
31.
go back to reference Sandhu SK, Schelman WR, Wilding G, Moreno V, Baird RD, Miranda S, et al. The poly(ADP-ribose) polymerase inhibitor niraparib (MK4827) in BRCA mutation carriers and patients with sporadic cancer: a phase 1 dose-escalation trial. Lancet Oncol. 2013;14:882–92. doi:10.1016/S1470-2045(13)70240-7.PubMed Sandhu SK, Schelman WR, Wilding G, Moreno V, Baird RD, Miranda S, et al. The poly(ADP-ribose) polymerase inhibitor niraparib (MK4827) in BRCA mutation carriers and patients with sporadic cancer: a phase 1 dose-escalation trial. Lancet Oncol. 2013;14:882–92. doi:10.​1016/​S1470-2045(13)70240-7.PubMed
32.
go back to reference De Bono JS, Mina LA, Gonzalez M, Curtin NJ, Wang E, Henshaw JW, et al. First-in-human trial of novel oral PARP inhibitor BMN 673 in patients with solid tumors. J Clin Oncol. 2013;31:2580. De Bono JS, Mina LA, Gonzalez M, Curtin NJ, Wang E, Henshaw JW, et al. First-in-human trial of novel oral PARP inhibitor BMN 673 in patients with solid tumors. J Clin Oncol. 2013;31:2580.
33.
go back to reference Kristeleit RS, Burris HA, LoRusso P, Patel MR, Asghar US, El-Khouly F, et al. Phase 1/2 study of oral rucaparib: final phase 1 results. J Clin Oncol. 2014;32:2573. Kristeleit RS, Burris HA, LoRusso P, Patel MR, Asghar US, El-Khouly F, et al. Phase 1/2 study of oral rucaparib: final phase 1 results. J Clin Oncol. 2014;32:2573.
34.
go back to reference Tutt A, Robson M, Garber JE, Domchek SM, Audeh MW, Weitzel JN, et al. Oral poly(ADP-ribose) polymerase inhibitor olaparib in patients with BRCA1 or BRCA2 mutations and advanced breast cancer: a proof-of-concept trial. Lancet. 2010;376:235–44. doi:10.1016/S0140-6736(10)60892-6.PubMed Tutt A, Robson M, Garber JE, Domchek SM, Audeh MW, Weitzel JN, et al. Oral poly(ADP-ribose) polymerase inhibitor olaparib in patients with BRCA1 or BRCA2 mutations and advanced breast cancer: a proof-of-concept trial. Lancet. 2010;376:235–44. doi:10.​1016/​S0140-6736(10)60892-6.PubMed
36.
go back to reference Martin M, Ruiz A, Munoz M, Balil A, Garcia-Mata J, Calvo L, et al. Gemcitabine plus vinorelbine versus vinorelbine monotherapy in patients with metastatic breast cancer previously treated with anthracyclines and taxanes: final results of the phase III Spanish Breast Cancer Research Group (GEICAM) trial. Lancet Oncol. 2007;8:219–25. doi:10.1016/S1470-2045(07)70041-4.PubMed Martin M, Ruiz A, Munoz M, Balil A, Garcia-Mata J, Calvo L, et al. Gemcitabine plus vinorelbine versus vinorelbine monotherapy in patients with metastatic breast cancer previously treated with anthracyclines and taxanes: final results of the phase III Spanish Breast Cancer Research Group (GEICAM) trial. Lancet Oncol. 2007;8:219–25. doi:10.​1016/​S1470-2045(07)70041-4.PubMed
37.
go back to reference Cortes J, O’Shaughnessy J, Loesch D, Blum JL, Vahdat LT, Petrakova K, et al. Eribulin monotherapy versus treatment of physician's choice in patients with metastatic breast cancer (EMBRACE): a phase 3 open-label randomised study. Lancet. 2011;377:914–23. doi:10.1016/S0140-6736(11)60070-6.PubMed Cortes J, O’Shaughnessy J, Loesch D, Blum JL, Vahdat LT, Petrakova K, et al. Eribulin monotherapy versus treatment of physician's choice in patients with metastatic breast cancer (EMBRACE): a phase 3 open-label randomised study. Lancet. 2011;377:914–23. doi:10.​1016/​S0140-6736(11)60070-6.PubMed
38.
go back to reference Low JA, Wedam SB, Lee JJ, Berman AW, Brufsky A, Yang SX, et al. Phase II clinical trial of ixabepilone (BMS-247550), an epothilone B analog, in metastatic and locally advanced breast cancer. J Clin Oncol. 2005;23:2726–34. doi:10.1200/JCO.2005.10.024.PubMed Low JA, Wedam SB, Lee JJ, Berman AW, Brufsky A, Yang SX, et al. Phase II clinical trial of ixabepilone (BMS-247550), an epothilone B analog, in metastatic and locally advanced breast cancer. J Clin Oncol. 2005;23:2726–34. doi:10.​1200/​JCO.​2005.​10.​024.PubMed
39.
go back to reference Perez EA, Lerzo G, Pivot X, Thomas E, Vahdat L, Bosserman L, et al. Efficacy and safety of ixabepilone (BMS-247550) in a phase II study of patients with advanced breast cancer resistant to an anthracycline, a taxane, and capecitabine. J Clin Oncol. 2007;25:3407–14. doi:10.1200/JCO.2006.09.3849.PubMed Perez EA, Lerzo G, Pivot X, Thomas E, Vahdat L, Bosserman L, et al. Efficacy and safety of ixabepilone (BMS-247550) in a phase II study of patients with advanced breast cancer resistant to an anthracycline, a taxane, and capecitabine. J Clin Oncol. 2007;25:3407–14. doi:10.​1200/​JCO.​2006.​09.​3849.PubMed
40.
go back to reference Thomas E, Tabernero J, Fornier M, Conte P, Fumoleau P, Lluch A, et al. Phase II clinical trial of ixabepilone (BMS-247550), an epothilone B analog, in patients with taxane-resistant metastatic breast cancer. J Clin Oncol. 2007;25:3399–406. doi:10.1200/JCO.2006.08.9102.PubMed Thomas E, Tabernero J, Fornier M, Conte P, Fumoleau P, Lluch A, et al. Phase II clinical trial of ixabepilone (BMS-247550), an epothilone B analog, in patients with taxane-resistant metastatic breast cancer. J Clin Oncol. 2007;25:3399–406. doi:10.​1200/​JCO.​2006.​08.​9102.PubMed
41.
go back to reference Baselga J, Gelmon KA, Verma S, Wardley A, Conte P, Miles D, et al. Phase II trial of pertuzumab and trastuzumab in patients with human epidermal growth factor receptor 2-positive metastatic breast cancer that progressed during prior trastuzumab therapy. J Clin Oncol. 2010;28:1138–44. doi:10.1200/JCO.2009.24.2024.PubMedPubMedCentral Baselga J, Gelmon KA, Verma S, Wardley A, Conte P, Miles D, et al. Phase II trial of pertuzumab and trastuzumab in patients with human epidermal growth factor receptor 2-positive metastatic breast cancer that progressed during prior trastuzumab therapy. J Clin Oncol. 2010;28:1138–44. doi:10.​1200/​JCO.​2009.​24.​2024.PubMedPubMedCentral
42.
go back to reference Verma S, Miles D, Gianni L, Krop IE, Welslau M, Baselga J, et al. Trastuzumab emtansine for HER2-positive advanced breast cancer. N Engl J Med. 2012;367:1783–91. doi:10.1056/NEJMoa1209124.PubMed Verma S, Miles D, Gianni L, Krop IE, Welslau M, Baselga J, et al. Trastuzumab emtansine for HER2-positive advanced breast cancer. N Engl J Med. 2012;367:1783–91. doi:10.​1056/​NEJMoa1209124.PubMed
43.
go back to reference Audeh MW, Carmichael J, Penson RT, Friedlander M, Powell B, Bell-McGuinn KM, et al. Oral poly(ADP-ribose) polymerase inhibitor olaparib in patients with BRCA1 or BRCA2 mutations and recurrent ovarian cancer: a proof-of-concept trial. Lancet. 2010;376:245–51. doi:10.1016/S0140-6736(10)60893-8.PubMed Audeh MW, Carmichael J, Penson RT, Friedlander M, Powell B, Bell-McGuinn KM, et al. Oral poly(ADP-ribose) polymerase inhibitor olaparib in patients with BRCA1 or BRCA2 mutations and recurrent ovarian cancer: a proof-of-concept trial. Lancet. 2010;376:245–51. doi:10.​1016/​S0140-6736(10)60893-8.PubMed
44.
go back to reference Ledermann J, Harter P, Gourley C, Friedlander M, Vergote I, Rustin G, et al. Olaparib maintenance therapy in platinum-sensitive relapsed ovarian cancer. N Engl J Med. 2012;366:1382–92. doi:10.1056/NEJMoa1105535.PubMed Ledermann J, Harter P, Gourley C, Friedlander M, Vergote I, Rustin G, et al. Olaparib maintenance therapy in platinum-sensitive relapsed ovarian cancer. N Engl J Med. 2012;366:1382–92. doi:10.​1056/​NEJMoa1105535.PubMed
45.
go back to reference Liu JF, Tolaney SM, Birrer M, Fleming GF, Buss MK, Dahlberg SE, et al. A Phase 1 trial of the poly(ADP-ribose) polymerase inhibitor olaparib (AZD2281) in combination with the anti-angiogenic cediranib (AZD2171) in recurrent epithelial ovarian or triple-negative breast cancer. Eur J Cancer. 2013;49:2972–8. doi:10.1016/j.ejca.2013.05.020.PubMedPubMedCentral Liu JF, Tolaney SM, Birrer M, Fleming GF, Buss MK, Dahlberg SE, et al. A Phase 1 trial of the poly(ADP-ribose) polymerase inhibitor olaparib (AZD2281) in combination with the anti-angiogenic cediranib (AZD2171) in recurrent epithelial ovarian or triple-negative breast cancer. Eur J Cancer. 2013;49:2972–8. doi:10.​1016/​j.​ejca.​2013.​05.​020.PubMedPubMedCentral
49.
go back to reference Coleman RL, Sill MW, Bell-McGuinn K, Aghajanian C, Gray HJ, Tewari KS, et al. A phase II evaluation of the potent, highly selective PARP inhibitor veliparib in the treatment of persistent or recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer in patients who carry a germline BRCA1 or BRCA2 mutation - An NRG Oncology/Gynecologic Oncology Group study. Gynecol Oncol. 2015;137:386–91. doi:10.1016/j.ygyno.2015.03.042.PubMedPubMedCentral Coleman RL, Sill MW, Bell-McGuinn K, Aghajanian C, Gray HJ, Tewari KS, et al. A phase II evaluation of the potent, highly selective PARP inhibitor veliparib in the treatment of persistent or recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer in patients who carry a germline BRCA1 or BRCA2 mutation - An NRG Oncology/Gynecologic Oncology Group study. Gynecol Oncol. 2015;137:386–91. doi:10.​1016/​j.​ygyno.​2015.​03.​042.PubMedPubMedCentral
50.
go back to reference Donawho CK, Luo Y, Luo Y, Penning TD, Bauch JL, Bouska JJ, et al. ABT-888, an orally active poly(ADP-ribose) polymerase inhibitor that potentiates DNA-damaging agents in preclinical tumor models. Clin Cancer Res. 2007;13:2728–37. doi:10.1158/1078-0432.CCR-06-3039.PubMed Donawho CK, Luo Y, Luo Y, Penning TD, Bauch JL, Bouska JJ, et al. ABT-888, an orally active poly(ADP-ribose) polymerase inhibitor that potentiates DNA-damaging agents in preclinical tumor models. Clin Cancer Res. 2007;13:2728–37. doi:10.​1158/​1078-0432.​CCR-06-3039.PubMed
51.
go back to reference Palma JP, Wang YC, Rodriguez LE, Montgomery D, Ellis PA, Bukofzer G, et al. ABT-888 confers broad in vivo activity in combination with temozolomide in diverse tumors. Clin Cancer Res. 2009;15:7277–90. doi:10.1158/1078-0432.CCR-09-1245.PubMed Palma JP, Wang YC, Rodriguez LE, Montgomery D, Ellis PA, Bukofzer G, et al. ABT-888 confers broad in vivo activity in combination with temozolomide in diverse tumors. Clin Cancer Res. 2009;15:7277–90. doi:10.​1158/​1078-0432.​CCR-09-1245.PubMed
52.
go back to reference Isakoff SJ, Overmoyer B, Tung NM, Gelman RS, Giranda VL, Bernhard KM, et al. A phase II trial of the PARP inhibitor veliparib (ABT888) and temozolomide for metastatic breast cancer. J Clin Oncol. 2010;28:1019. Isakoff SJ, Overmoyer B, Tung NM, Gelman RS, Giranda VL, Bernhard KM, et al. A phase II trial of the PARP inhibitor veliparib (ABT888) and temozolomide for metastatic breast cancer. J Clin Oncol. 2010;28:1019.
53.
go back to reference Rodler ET, Gralow J, Kurland BF, Griffin M, Yeh R, Thompson JA, et al. Phase I: Veliparib with cisplatin (CP) and vinorelbine (VNR) in advanced triple-negative breast cancer (TNBC) and/or BRCA mutation-associated breast cancer. J Clin Oncol. 2014;32:2569. Rodler ET, Gralow J, Kurland BF, Griffin M, Yeh R, Thompson JA, et al. Phase I: Veliparib with cisplatin (CP) and vinorelbine (VNR) in advanced triple-negative breast cancer (TNBC) and/or BRCA mutation-associated breast cancer. J Clin Oncol. 2014;32:2569.
54.
go back to reference Somlo G, Frankel PH, Luu TH, Ma C, Arun B, Garcia A, et al. Efficacy of the combination of ABT-888 (veliparib) and carboplatin in patients with BRCA-associated breast cancer. J Clin Oncol. 2013;31:1024. Somlo G, Frankel PH, Luu TH, Ma C, Arun B, Garcia A, et al. Efficacy of the combination of ABT-888 (veliparib) and carboplatin in patients with BRCA-associated breast cancer. J Clin Oncol. 2013;31:1024.
55.
go back to reference Pahuja S, Beumer JH, Appleman LJ, Tawbi HA, Stoller RG, Lee JJ, et al. A phase I study of veliparib (ABT-888) in combination with weekly carboplatin and paclitaxel in advanced solid malignancies and enriched for triple-negative breast cancer (TNBC). J Clin Oncol. 2015;33:1015. Pahuja S, Beumer JH, Appleman LJ, Tawbi HA, Stoller RG, Lee JJ, et al. A phase I study of veliparib (ABT-888) in combination with weekly carboplatin and paclitaxel in advanced solid malignancies and enriched for triple-negative breast cancer (TNBC). J Clin Oncol. 2015;33:1015.
57.
go back to reference Samol J, Ranson M, Scott E, Macpherson E, Carmichael J, Thomas A, et al. Safety and tolerability of the poly(ADP-ribose) polymerase (PARP) inhibitor, olaparib (AZD2281) in combination with topotecan for the treatment of patients with advanced solid tumors: a phase I study. Invest New Drugs. 2012;30:1493–500. doi:10.1007/s10637-011-9682-9.PubMed Samol J, Ranson M, Scott E, Macpherson E, Carmichael J, Thomas A, et al. Safety and tolerability of the poly(ADP-ribose) polymerase (PARP) inhibitor, olaparib (AZD2281) in combination with topotecan for the treatment of patients with advanced solid tumors: a phase I study. Invest New Drugs. 2012;30:1493–500. doi:10.​1007/​s10637-011-9682-9.PubMed
58.
go back to reference Murai J, Zhang Y, Morris J, Ji J, Takeda S, Doroshow JH, et al. Rationale for poly(ADP-ribose) polymerase (PARP) inhibitors in combination therapy with camptothecins or temozolomide based on PARP trapping versus catalytic inhibition. J Pharmacol Exp Ther. 2014;349:408–16. doi:10.1124/jpet.113.210146.PubMedPubMedCentral Murai J, Zhang Y, Morris J, Ji J, Takeda S, Doroshow JH, et al. Rationale for poly(ADP-ribose) polymerase (PARP) inhibitors in combination therapy with camptothecins or temozolomide based on PARP trapping versus catalytic inhibition. J Pharmacol Exp Ther. 2014;349:408–16. doi:10.​1124/​jpet.​113.​210146.PubMedPubMedCentral
59.
go back to reference Rottenberg S, Jaspers JE, Kersbergen A, van der Burg E, Nygren AO, Zander SA, et al. High sensitivity of BRCA1-deficient mammary tumors to the PARP inhibitor AZD2281 alone and in combination with platinum drugs. Proc Natl Acad Sci U S A. 2008;105:17079–84. doi:10.1073/pnas.0806092105.PubMedPubMedCentral Rottenberg S, Jaspers JE, Kersbergen A, van der Burg E, Nygren AO, Zander SA, et al. High sensitivity of BRCA1-deficient mammary tumors to the PARP inhibitor AZD2281 alone and in combination with platinum drugs. Proc Natl Acad Sci U S A. 2008;105:17079–84. doi:10.​1073/​pnas.​0806092105.PubMedPubMedCentral
66.
go back to reference Oza AM, Cibula D, Benzaquen AO, Poole C, Mathijssen RH, Sonke GS, et al. Olaparib combined with chemotherapy for recurrent platinum-sensitive ovarian cancer: a randomised phase 2 trial. Lancet Oncol. 2015;16:87–97. doi:10.1016/S1470-2045(14)71135-0.PubMed Oza AM, Cibula D, Benzaquen AO, Poole C, Mathijssen RH, Sonke GS, et al. Olaparib combined with chemotherapy for recurrent platinum-sensitive ovarian cancer: a randomised phase 2 trial. Lancet Oncol. 2015;16:87–97. doi:10.​1016/​S1470-2045(14)71135-0.PubMed
67.
go back to reference Tutt A, Kaufman B, Gelber R, McFadden E, Goessl CD, Viale G, et al. OlympiA: A randomized phase III trial of olaparib as adjuvant therapy in patients with high-risk HER2-negative breast cancer (BC) and a germline BRCA1/2 mutation (gBRCAm). J Clin Oncol. 2015;33, TPS1109. Tutt A, Kaufman B, Gelber R, McFadden E, Goessl CD, Viale G, et al. OlympiA: A randomized phase III trial of olaparib as adjuvant therapy in patients with high-risk HER2-negative breast cancer (BC) and a germline BRCA1/2 mutation (gBRCAm). J Clin Oncol. 2015;33, TPS1109.
70.
go back to reference Dwadasi S, Tong Y, Walsh T, Danso MA, Ma CX, Silverman P, et al. Cisplatin with or without rucaparib after preoperative chemotherapy in patients with triple-negative breast cancer (TNBC): Hoosier Oncology Group BRE09-146. J Clin Oncol. 2014;32:1019. Dwadasi S, Tong Y, Walsh T, Danso MA, Ma CX, Silverman P, et al. Cisplatin with or without rucaparib after preoperative chemotherapy in patients with triple-negative breast cancer (TNBC): Hoosier Oncology Group BRE09-146. J Clin Oncol. 2014;32:1019.
71.
go back to reference Rugo HS, Olopade O, DeMichele A, van’t Veer L, Buxton M, Hylton N, et al. Veliparib/carboplatin plus standard neoadjuvant therapy for high-risk breast cancer: first efficacy results from the I-SPY 2 TRIAL. Cancer Res. 2013;73:S5–02. Rugo HS, Olopade O, DeMichele A, van’t Veer L, Buxton M, Hylton N, et al. Veliparib/carboplatin plus standard neoadjuvant therapy for high-risk breast cancer: first efficacy results from the I-SPY 2 TRIAL. Cancer Res. 2013;73:S5–02.
72.
go back to reference von Minckwitz G, Schneeweiss A, Loibl S, Salat C, Denkert C, Rezai M, et al. Neoadjuvant carboplatin in patients with triple-negative and HER2-positive early breast cancer (GeparSixto; GBG 66): a randomised phase 2 trial. Lancet Oncol. 2014;15:747–56. doi:10.1016/S1470-2045(14)70160-3. von Minckwitz G, Schneeweiss A, Loibl S, Salat C, Denkert C, Rezai M, et al. Neoadjuvant carboplatin in patients with triple-negative and HER2-positive early breast cancer (GeparSixto; GBG 66): a randomised phase 2 trial. Lancet Oncol. 2014;15:747–56. doi:10.​1016/​S1470-2045(14)70160-3.
73.
go back to reference Sikov WM, Berry DA, Perou CM, Singh B, Cirrincione CT, Tolaney SM, 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 Clin Oncol. 2015;33:13–21. doi:10.1200/JCO.2014.57.0572.PubMed Sikov WM, Berry DA, Perou CM, Singh B, Cirrincione CT, Tolaney SM, 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 Clin Oncol. 2015;33:13–21. doi:10.​1200/​JCO.​2014.​57.​0572.PubMed
74.
go back to reference AbbVie. A study evaluating safety and efficacy of the addition of ABT-888 plus carboplatin versus the addition of carboplatin to standard chemotherapy versus standard chemotherapy in subjects with early stage triple negative breast cancer. https://clinicaltrials.gov/ct2/show/NCT02032277. Accessed 15 Jun 2015. AbbVie. A study evaluating safety and efficacy of the addition of ABT-888 plus carboplatin versus the addition of carboplatin to standard chemotherapy versus standard chemotherapy in subjects with early stage triple negative breast cancer. https://​clinicaltrials.​gov/​ct2/​show/​NCT02032277. Accessed 15 Jun 2015.
76.
go back to reference To C, Kim EH, Royce DB, Williams CR, Collins RM, Risingsong R, et al. The PARP inhibitors, veliparib and olaparib, are effective chemopreventive agents for delaying mammary tumor development in BRCA1-deficient mice. Cancer Prev Res (Phila). 2014;7:698–707. doi:10.1158/1940-6207.CAPR-14-0047. To C, Kim EH, Royce DB, Williams CR, Collins RM, Risingsong R, et al. The PARP inhibitors, veliparib and olaparib, are effective chemopreventive agents for delaying mammary tumor development in BRCA1-deficient mice. Cancer Prev Res (Phila). 2014;7:698–707. doi:10.​1158/​1940-6207.​CAPR-14-0047.
77.
go back to reference Khan OA, Gore M, Lorigan P, Stone J, Greystoke A, Burke W, et al. A phase I study of the safety and tolerability of olaparib (AZD2281, KU0059436) and dacarbazine in patients with advanced solid tumours. Br J Cancer. 2011;104:750–5. doi:10.1038/bjc.2011.8.PubMedPubMedCentral Khan OA, Gore M, Lorigan P, Stone J, Greystoke A, Burke W, et al. A phase I study of the safety and tolerability of olaparib (AZD2281, KU0059436) and dacarbazine in patients with advanced solid tumours. Br J Cancer. 2011;104:750–5. doi:10.​1038/​bjc.​2011.​8.PubMedPubMedCentral
78.
go back to reference Rajan A, Carter CA, Kelly RJ, Gutierrez M, Kummar S, Szabo E, et al. A phase I combination study of olaparib with cisplatin and gemcitabine in adults with solid tumors. Clin Cancer Res. 2012;18:2344–51. doi:10.1158/1078-0432.CCR-11-2425.PubMed Rajan A, Carter CA, Kelly RJ, Gutierrez M, Kummar S, Szabo E, et al. A phase I combination study of olaparib with cisplatin and gemcitabine in adults with solid tumors. Clin Cancer Res. 2012;18:2344–51. doi:10.​1158/​1078-0432.​CCR-11-2425.PubMed
79.
go back to reference Dean E, Middleton MR, Pwint T, Swaisland H, Carmichael J, Goodege-Kunwar P, et al. Phase I study to assess the safety and tolerability of olaparib in combination with bevacizumab in patients with advanced solid tumours. Br J Cancer. 2012;106:468–74. doi:10.1038/bjc.2011.555.PubMedPubMedCentral Dean E, Middleton MR, Pwint T, Swaisland H, Carmichael J, Goodege-Kunwar P, et al. Phase I study to assess the safety and tolerability of olaparib in combination with bevacizumab in patients with advanced solid tumours. Br J Cancer. 2012;106:468–74. doi:10.​1038/​bjc.​2011.​555.PubMedPubMedCentral
80.
go back to reference Rogakou EP, Pilch DR, Orr AH, Ivanova VS, Bonner WM. DNA double-stranded breaks induce histone H2AX phosphorylation on serine 139. J Biol Chem. 1998;273:5858–68.PubMed Rogakou EP, Pilch DR, Orr AH, Ivanova VS, Bonner WM. DNA double-stranded breaks induce histone H2AX phosphorylation on serine 139. J Biol Chem. 1998;273:5858–68.PubMed
86.
go back to reference Edwards SL, Brough R, Lord CJ, Natrajan R, Vatcheva R, Levine DA, et al. Resistance to therapy caused by intragenic deletion in BRCA2. Nature. 2008;451:1111–5. doi:10.1038/nature06548.PubMed Edwards SL, Brough R, Lord CJ, Natrajan R, Vatcheva R, Levine DA, et al. Resistance to therapy caused by intragenic deletion in BRCA2. Nature. 2008;451:1111–5. doi:10.​1038/​nature06548.PubMed
89.
go back to reference Wurzer G, Herceg Z, Wesierska-Gadek J. Increased resistance to anticancer therapy of mouse cells lacking the poly(ADP-ribose) polymerase attributable to up-regulation of the multidrug resistance gene product P-glycoprotein. Cancer Res. 2000;60:4238–44.PubMed Wurzer G, Herceg Z, Wesierska-Gadek J. Increased resistance to anticancer therapy of mouse cells lacking the poly(ADP-ribose) polymerase attributable to up-regulation of the multidrug resistance gene product P-glycoprotein. Cancer Res. 2000;60:4238–44.PubMed
90.
go back to reference Bouwman P, Aly A, Escandell JM, Pieterse M, Bartkova J, van der Gulden H, et al. 53BP1 loss rescues BRCA1 deficiency and is associated with triple-negative and BRCA-mutated breast cancers. Nat Struct Mol Biol. 2010;17:688–95. doi:10.1038/nsmb.1831.PubMedPubMedCentral Bouwman P, Aly A, Escandell JM, Pieterse M, Bartkova J, van der Gulden H, et al. 53BP1 loss rescues BRCA1 deficiency and is associated with triple-negative and BRCA-mutated breast cancers. Nat Struct Mol Biol. 2010;17:688–95. doi:10.​1038/​nsmb.​1831.PubMedPubMedCentral
92.
93.
go back to reference Oplustilova L, Wolanin K, Mistrik M, Korinkova G, Simkova D, Bouchal J, et al. Evaluation of candidate biomarkers to predict cancer cell sensitivity or resistance to PARP-1 inhibitor treatment. Cell Cycle. 2012;11:3837–50. doi:10.4161/cc.22026.PubMedPubMedCentral Oplustilova L, Wolanin K, Mistrik M, Korinkova G, Simkova D, Bouchal J, et al. Evaluation of candidate biomarkers to predict cancer cell sensitivity or resistance to PARP-1 inhibitor treatment. Cell Cycle. 2012;11:3837–50. doi:10.​4161/​cc.​22026.PubMedPubMedCentral
95.
go back to reference Ang JE, Gourley C, Powell CB, High H, Shapira-Frommer R, Castonguay V, et al. Efficacy of chemotherapy in BRCA1/2 mutation carrier ovarian cancer in the setting of PARP inhibitor resistance: a multi-institutional study. Clin Cancer Res. 2013;19:5485–93. doi:10.1158/1078-0432.CCR-13-1262.PubMed Ang JE, Gourley C, Powell CB, High H, Shapira-Frommer R, Castonguay V, et al. Efficacy of chemotherapy in BRCA1/2 mutation carrier ovarian cancer in the setting of PARP inhibitor resistance: a multi-institutional study. Clin Cancer Res. 2013;19:5485–93. doi:10.​1158/​1078-0432.​CCR-13-1262.PubMed
96.
go back to reference AbbVie. The study evaluating efficacy and tolerability of veliparib in combination with temozolomide or in combination with carboplatin and paclitaxel versus placebo in subjects with BRCA1 and BRCA2 mutation and metastatic breast cancer. https://clinicaltrials.gov/ct2/show/NCT01506609. Accessed 15 Jun 2015. AbbVie. The study evaluating efficacy and tolerability of veliparib in combination with temozolomide or in combination with carboplatin and paclitaxel versus placebo in subjects with BRCA1 and BRCA2 mutation and metastatic breast cancer. https://​clinicaltrials.​gov/​ct2/​show/​NCT01506609. Accessed 15 Jun 2015.
99.
100.
go back to reference Richardson AL, Silver DP, Szallasi Z, Birkbak NJ, Wang ZC, Iglehart JD, et al. Homologous recombination deficiency (HRD) score predicts response to cisplatin neoadjuvant chemotherapy in patients with triple negative breast cancer. San Antonio Breast Cancer Symposium Proceedings. 2014;2014:P3-06-11. Richardson AL, Silver DP, Szallasi Z, Birkbak NJ, Wang ZC, Iglehart JD, et al. Homologous recombination deficiency (HRD) score predicts response to cisplatin neoadjuvant chemotherapy in patients with triple negative breast cancer. San Antonio Breast Cancer Symposium Proceedings. 2014;2014:P3-06-11.
101.
go back to reference Telli ML, Timms K, Reid JE, Neff C, Abkevich V, Gutin A, et al. Combined homologous recombination deficiency (HRD) scores and response to neoadjuvant platinum-based chemotherapy in triple-negative and/or BRCA1/2 mutation-associated breast cancer. J Clin Oncol. 2015;33:1018. Telli ML, Timms K, Reid JE, Neff C, Abkevich V, Gutin A, et al. Combined homologous recombination deficiency (HRD) scores and response to neoadjuvant platinum-based chemotherapy in triple-negative and/or BRCA1/2 mutation-associated breast cancer. J Clin Oncol. 2015;33:1018.
102.
go back to reference von Minckwitz G, Timms K, Untch M, Elkin EP, Fasching PA, Schneeweiss A, et al. Prediction of pathological complete response (pCR) by homologous recombination deficiency (HRD) after carboplatin-containing neoadjuvant chemotherapy in patients with TNBC: results from GeparSixto. J Clin Oncol. 2015;33:1004. von Minckwitz G, Timms K, Untch M, Elkin EP, Fasching PA, Schneeweiss A, et al. Prediction of pathological complete response (pCR) by homologous recombination deficiency (HRD) after carboplatin-containing neoadjuvant chemotherapy in patients with TNBC: results from GeparSixto. J Clin Oncol. 2015;33:1004.
103.
go back to reference Tutt A, Ellis P, Kilburn L, Gilett C, Pinder S, Abraham J, et al. TNT: a randomized phase III trial of carboplatin (C) compared with docetaxel (D) for patients with metastatic or recurrent locally advanced triple negative or BRCA1/2 breast cancer (CRUK/07/012). San Antonio Breast Cancer Symposium Proceedings. 2014;2014:S3–01. Tutt A, Ellis P, Kilburn L, Gilett C, Pinder S, Abraham J, et al. TNT: a randomized phase III trial of carboplatin (C) compared with docetaxel (D) for patients with metastatic or recurrent locally advanced triple negative or BRCA1/2 breast cancer (CRUK/07/012). San Antonio Breast Cancer Symposium Proceedings. 2014;2014:S3–01.
106.
go back to reference Gottipati P, Vischioni B, Schultz N, Solomons J, Bryant HE, Djureinovic T, et al. Poly(ADP-ribose) polymerase is hyperactivated in homologous recombination-defective cells. Cancer Res. 2010;70:5389–98. doi:10.1158/0008-5472.CAN-09-4716.PubMed Gottipati P, Vischioni B, Schultz N, Solomons J, Bryant HE, Djureinovic T, et al. Poly(ADP-ribose) polymerase is hyperactivated in homologous recombination-defective cells. Cancer Res. 2010;70:5389–98. doi:10.​1158/​0008-5472.​CAN-09-4716.PubMed
107.
go back to reference Balmana J, Domchek SM, Tutt A, Garber JE. Stumbling blocks on the path to personalized medicine in breast cancer: the case of PARP inhibitors for BRCA1/2-associated cancers. Cancer Discov. 2011;1:29–34. doi:10.1158/2159-8274.CD-11-0048.PubMed Balmana J, Domchek SM, Tutt A, Garber JE. Stumbling blocks on the path to personalized medicine in breast cancer: the case of PARP inhibitors for BRCA1/2-associated cancers. Cancer Discov. 2011;1:29–34. doi:10.​1158/​2159-8274.​CD-11-0048.PubMed
109.
111.
go back to reference Weston VJ, Oldreive CE, Skowronska A, Oscier DG, Pratt G, Dyer MJ, et al. The PARP inhibitor olaparib induces significant killing of ATM-deficient lymphoid tumor cells in vitro and in vivo. Blood. 2010;116:4578–87. doi:10.1182/blood-2010-01-265769.PubMed Weston VJ, Oldreive CE, Skowronska A, Oscier DG, Pratt G, Dyer MJ, et al. The PARP inhibitor olaparib induces significant killing of ATM-deficient lymphoid tumor cells in vitro and in vivo. Blood. 2010;116:4578–87. doi:10.​1182/​blood-2010-01-265769.PubMed
113.
go back to reference Ha K, Fiskus W, Choi DS, Bhaskara S, Cerchietti L, Devaraj SG, et al. Histone deacetylase inhibitor treatment induces ‘BRCAness’ and synergistic lethality with PARP inhibitor and cisplatin against human triple negative breast cancer cells. Oncotarget. 2014;5:5637–50.PubMedPubMedCentral Ha K, Fiskus W, Choi DS, Bhaskara S, Cerchietti L, Devaraj SG, et al. Histone deacetylase inhibitor treatment induces ‘BRCAness’ and synergistic lethality with PARP inhibitor and cisplatin against human triple negative breast cancer cells. Oncotarget. 2014;5:5637–50.PubMedPubMedCentral
115.
go back to reference De P, Sun Y, Carlson JH, Friedman LS, Leyland-Jones BR, Dey N. Doubling down on the PI3K-AKT-mTOR pathway enhances the antitumor efficacy of PARP inhibitor in triple negative breast cancer model beyond BRCA-ness. Neoplasia. 2014;16:43–72.PubMedPubMedCentral De P, Sun Y, Carlson JH, Friedman LS, Leyland-Jones BR, Dey N. Doubling down on the PI3K-AKT-mTOR pathway enhances the antitumor efficacy of PARP inhibitor in triple negative breast cancer model beyond BRCA-ness. Neoplasia. 2014;16:43–72.PubMedPubMedCentral
118.
go back to reference Matulonis U, Wulf G, Barry W, Birrer M, Westin S, Spagnoletti T, et al. Phase I of oral BKM120 or BLY719 and olaparib for high-grade serous ovarian cancer or triple-negative breast cancer: Final results of the BKM120 plus olaparib cohort. Proceedings of the 106th Annual Meeting of the American Association for Cancer Research. 2015 Apr 18–22:CT324. Matulonis U, Wulf G, Barry W, Birrer M, Westin S, Spagnoletti T, et al. Phase I of oral BKM120 or BLY719 and olaparib for high-grade serous ovarian cancer or triple-negative breast cancer: Final results of the BKM120 plus olaparib cohort. Proceedings of the 106th Annual Meeting of the American Association for Cancer Research. 2015 Apr 18–22:CT324.
119.
120.
go back to reference Pahuja S, Beumer JH, Appleman LJ, Tawbi HA, Stoller RG, Lee JJ, et al. Outcome of BRCA 1/2-mutated (BRCA+) and triple-negative, BRCA wild type (BRCA-wt) breast cancer patients in a phase I study of single-agent veliparib (V). J Clin Oncol. 2014;32:135. Pahuja S, Beumer JH, Appleman LJ, Tawbi HA, Stoller RG, Lee JJ, et al. Outcome of BRCA 1/2-mutated (BRCA+) and triple-negative, BRCA wild type (BRCA-wt) breast cancer patients in a phase I study of single-agent veliparib (V). J Clin Oncol. 2014;32:135.
121.
go back to reference Drew Y, Ledermann JA, Jones A, Hall G, Jayson GC, Highley M, et al. Phase II trial of the poly(ADP-ribose) polymerase (PARP) inhibitor AG-014699 in BRCA-1 and -2 mutated, advanced ovarian and/or locally advanced or metastatic breast cancer. J Clin Oncol. 2011;29:3104. Drew Y, Ledermann JA, Jones A, Hall G, Jayson GC, Highley M, et al. Phase II trial of the poly(ADP-ribose) polymerase (PARP) inhibitor AG-014699 in BRCA-1 and -2 mutated, advanced ovarian and/or locally advanced or metastatic breast cancer. J Clin Oncol. 2011;29:3104.
122.
go back to reference Dent RA, Lindeman GJ, Clemons M, Wildiers H, Chan A, McCarthy NJ, et al. Phase I trial of the oral PARP inhibitor olaparib in combination with paclitaxel for first- or second-line treatment of patients with metastatic triple-negative breast cancer. Breast Cancer Res. 2013;15:R88. doi:10.1186/bcr3484.PubMedPubMedCentral Dent RA, Lindeman GJ, Clemons M, Wildiers H, Chan A, McCarthy NJ, et al. Phase I trial of the oral PARP inhibitor olaparib in combination with paclitaxel for first- or second-line treatment of patients with metastatic triple-negative breast cancer. Breast Cancer Res. 2013;15:R88. doi:10.​1186/​bcr3484.PubMedPubMedCentral
123.
go back to reference Lee JM, Hays JL, Annunziata CM, Noonan AM, Minasian L, Zujewski JA, et al. Phase I/Ib study of olaparib and carboplatin in BRCA1 or BRCA2 mutation-associated breast or ovarian cancer with biomarker analyses. J Natl Cancer Inst. 2014;106:dju089. Lee JM, Hays JL, Annunziata CM, Noonan AM, Minasian L, Zujewski JA, et al. Phase I/Ib study of olaparib and carboplatin in BRCA1 or BRCA2 mutation-associated breast or ovarian cancer with biomarker analyses. J Natl Cancer Inst. 2014;106:dju089.
124.
go back to reference Appleman LJ, Beumer JH, Jiang Y, Puhalla S, Lin Y, Owonikoko TK, et al. A phase I study of veliparib (ABT-888) in combination with carboplatin and paclitaxel in advanced solid malignancies. J Clin Oncol. 2012;30:3049. Appleman LJ, Beumer JH, Jiang Y, Puhalla S, Lin Y, Owonikoko TK, et al. A phase I study of veliparib (ABT-888) in combination with carboplatin and paclitaxel in advanced solid malignancies. J Clin Oncol. 2012;30:3049.
125.
go back to reference Tan AR, Toppmeyer D, Stein MN, Moss RA, Gounder M, Lindquist DC, et al. Phase I trial of veliparib, (ABT-888), a poly(ADP-ribose) polymerase (PARP) inhibitor, in combination with doxorubicin and cyclophosphamide in breast cancer and other solid tumors. J Clin Oncol. 2011;29:3041. Tan AR, Toppmeyer D, Stein MN, Moss RA, Gounder M, Lindquist DC, et al. Phase I trial of veliparib, (ABT-888), a poly(ADP-ribose) polymerase (PARP) inhibitor, in combination with doxorubicin and cyclophosphamide in breast cancer and other solid tumors. J Clin Oncol. 2011;29:3041.
126.
go back to reference Bell-McGuinn KM, Gray HJ, Fleming GF, Cristea MC, Medina DM, Xiong H, et al. Phase I study of ABT-888 in combination with carboplatin and gemcitabine in subjects with advanced solid tumors. J Clin Oncol. 2013;31:2584. Bell-McGuinn KM, Gray HJ, Fleming GF, Cristea MC, Medina DM, Xiong H, et al. Phase I study of ABT-888 in combination with carboplatin and gemcitabine in subjects with advanced solid tumors. J Clin Oncol. 2013;31:2584.
127.
go back to reference Wesolowski R, Zhao M, Geyer SM, Lustberg MB, Mrozek E, Layman RM, et al. Phase I trial of the PARP inhibitor veliparib (V) in combination with carboplatin (C) in metastatic breast cancer (MBC). J Clin Oncol. 2014;32:1075. Wesolowski R, Zhao M, Geyer SM, Lustberg MB, Mrozek E, Layman RM, et al. Phase I trial of the PARP inhibitor veliparib (V) in combination with carboplatin (C) in metastatic breast cancer (MBC). J Clin Oncol. 2014;32:1075.
129.
go back to reference Molife LR, Roxburgh P, Wilson RH, Gupta A, Middleton MR, Evans TRJ, et al. A phase I study of oral rucaparib in combination with carboplatin. J Clin Oncol. 2013;31:2586. Molife LR, Roxburgh P, Wilson RH, Gupta A, Middleton MR, Evans TRJ, et al. A phase I study of oral rucaparib in combination with carboplatin. J Clin Oncol. 2013;31:2586.
130.
go back to reference Plummer R, Stephens P, Aissat-Daudigny L, Cambois A, Moachon G, Brown PD, et al. Phase 1 dose-escalation study of the PARP inhibitor CEP-9722 as monotherapy or in combination with temozolomide in patients with solid tumors. Cancer Chemother Pharmacol. 2014;74:257–65. doi:10.1007/s00280-014-2486-9.PubMedPubMedCentral Plummer R, Stephens P, Aissat-Daudigny L, Cambois A, Moachon G, Brown PD, et al. Phase 1 dose-escalation study of the PARP inhibitor CEP-9722 as monotherapy or in combination with temozolomide in patients with solid tumors. Cancer Chemother Pharmacol. 2014;74:257–65. doi:10.​1007/​s00280-014-2486-9.PubMedPubMedCentral
134.
go back to reference Bundred N, Gardovskis J, Jaskiewicz J, Eglitis J, Paramonov V, McCormack P, et al. Evaluation of the pharmacodynamics and pharmacokinetics of the PARP inhibitor olaparib: a phase I multicentre trial in patients scheduled for elective breast cancer surgery. Invest New Drugs. 2013;31:949–58. doi:10.1007/s10637-012-9922-7.PubMed Bundred N, Gardovskis J, Jaskiewicz J, Eglitis J, Paramonov V, McCormack P, et al. Evaluation of the pharmacodynamics and pharmacokinetics of the PARP inhibitor olaparib: a phase I multicentre trial in patients scheduled for elective breast cancer surgery. Invest New Drugs. 2013;31:949–58. doi:10.​1007/​s10637-012-9922-7.PubMed
135.
Metadata
Title
PARP inhibitors in the management of breast cancer: current data and future prospects
Authors
Luca Livraghi
Judy E. Garber
Publication date
01-12-2015
Publisher
BioMed Central
Published in
BMC Medicine / Issue 1/2015
Electronic ISSN: 1741-7015
DOI
https://doi.org/10.1186/s12916-015-0425-1

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