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Systemic therapy options in BRCA mutation-associated breast cancer

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Abstract

BRCA mutation-associated breast cancers are characterized by deficient homologous recombination of DNA, and 80 % of BRCA1-associated breast cancers display the basal-like molecular subtype. Traditionally, BRCA carriers have received conventional systemic chemotherapy based on their baseline tumor characteristics, and it is generally accepted that after the appropriate treatment the prognosis of a mutation carrier is equivalent to that of a patient with sporadic breast cancer. However, with the growing understanding of the functions of BRCA1/2 proteins in homologous DNA repair, it is recognized that BRCA-associated breast cancer tumors may have distinct biochemical characteristics and thus require tailored treatment strategies. Tumors arising in patients with BRCA mutations were shown to be particularly sensitive to platinum compounds or inhibitors of poly(ADP-ribose) polymerase. In addition, BRCA1-mutation carriers seem to benefit from anthracycline–taxane-containing regimens as much as sporadic triple-negative breast cancers do. In this article, we review the functions of the BRCA1 and BRCA2 genes, and their differential chemosensitivity in both the preclinical and clinical settings. The optimal chemotherapy regimen for this subset of patients still remains to be determined.

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References

  1. Siegel R, Naishadham D, Jemal A (2012) Cancer statistics 2012. CA Cancer J Clin 62:10–29

    Article  PubMed  Google Scholar 

  2. Chen S, Iversen ES, Friebel T, Finkelstein D et al (2006) Characterization of BRCA1 and BRCA2 mutations in a large United States sample. J Clin Oncol 24:863–871

    Article  PubMed  CAS  Google Scholar 

  3. Antoniou A, Pharoah PD, Narod S et al (2003) Average risks of breast and ovarian cancer associated with BRCA1 or BRCA2 mutations detected in case Series unselected for family history: a combined analysis of 22 studies. Am J Hum Genet 72:1117–1130

    Article  PubMed  CAS  Google Scholar 

  4. Seynaeve C, Verhoog LC, van de Bosch LM et al (2004) Ipsilateral breast tumour recurrence in hereditary breast cancer following breast-conserving therapy. Eur J Cancer 40:1150–1158

    Article  PubMed  CAS  Google Scholar 

  5. Kirova YM, Stoppa-Lyonnet D, Savignoni A, Sigal-Zafrani B, Fabre N, Fourquet A et al (2005) Risk of breast cancer recurrence and contralateral breast cancer in relation to BRCA1 and BRCA2 mutation status following breast-conserving surgery and radiotherapy. Eur J Cancer 41:2304–2311

    Article  PubMed  Google Scholar 

  6. Moller P, Evans DG, Reis MM et al (2007) Surveillance for familial breast cancer: differences in outcome according to BRCA mutation status. Int J Cancer 121:1017–1020

    Article  PubMed  CAS  Google Scholar 

  7. Verhoog LC, Brekelmans CT, Seynaeve C et al (1999) Survival in hereditary breast cancer associated with germline mutations of BRCA2. J Clin Oncol 17:3396–3402

    PubMed  CAS  Google Scholar 

  8. Rennert G, Bisland-Naggan S, Barnett-Griness O, Bar-Joseph N, Zhang S, Rennert HS, Narod SA (2007) Clinical outcomes of breast cancer in carriers of BRCA1 and BRCA2 mutations. The New England journal of medicine 357:115–123

    Article  PubMed  CAS  Google Scholar 

  9. Byrski T, Gronwald J, Huzarski T, Grzybowska E, Budryk M, Stawicka M, Mierzwa T, Szwiec M, Wisniowski R, Siolek M, Dent R, Lubinski J, Narod S (2010) Pathologic complete response rates in young women with BRCA1-positive breast cancers after neoadjuvant chemotherapy. J Clin Oncol 28:375–379

    Article  PubMed  CAS  Google Scholar 

  10. Arun B, Bayraktar S, Liu DD, Gutierrez Barrera AM, Atchley D, Pusztai L, Litton JK, Valero V, Meric-Bernstam F, Hortobagyi GN, Albarracin C (2011) Response to neoadjuvant systemic therapy for breast cancer in BRCA mutation carriers and noncarriers: a single-institution experience. J Clin Oncol 29:3739–3746

    Article  PubMed  CAS  Google Scholar 

  11. Wen J, Li R, Lu Y, Shupnik MA (2009) Decreased BRCA1 confers tamoxifen resistance in breast cancer cells by altering estrogen receptor-coregulator interactions. Oncogene 28:575–586

    Article  PubMed  Google Scholar 

  12. Fong PC, Boss DS, Yap TA, Tutt A, Wu P, Mergui-Roelvink M, Mortimer P, Swaisland H, Lau A, O’Connor MJ, Ashworth A, Carmichael J, Kaye SB, Schellens JH, de Bono JS (2009) Inhibition of poly(ADP-ribose) polymerase in tumors from BRCA mutation carriers. New Engl J Med 361:123–134

    Article  PubMed  CAS  Google Scholar 

  13. Zhang J, Powell SN (2005) The role of the BRCA1 tumor suppressor in DNA double-strand break repair. Mol Cancer Res 3:531–539

    Article  PubMed  CAS  Google Scholar 

  14. Xu B, Kim S, Kastan MB (2001) Involvement of Brca1 in S-phase and G(2)-phase checkpoints after ionizing irradiation. Mol Cell Biol 21:3445–3450

    Article  PubMed  CAS  Google Scholar 

  15. Yun MH, Hiom K (2009) Understanding the functions of BRCA1 in the DNA-damage response. Biochem Soc Trans 37:597–604

    Article  PubMed  CAS  Google Scholar 

  16. Narod SA, Foulkes WD (2004) BRCA1 and BRCA2: 1994 and beyond. Nat Rev Cancer 4:665–676

    Article  PubMed  CAS  Google Scholar 

  17. Wong AK, Pero R, Ormonde PA, Tavtigian SV, Bartel PL (1997) RAD51 interacts with the evolutionarily conserved BRC motifs in the human breast cancer susceptibility gene brca2. J Biol Chem 272:31941–31944

    Article  PubMed  CAS  Google Scholar 

  18. Da Silva L, Lakhani SR (2010) Pathology of hereditary breast cancer. Mod Pathol 23(Suppl 2):S46–S51

    Article  PubMed  Google Scholar 

  19. Meyer P, Landgraf K, Hogel B, Eiermann W, Ataseven B (2012) BRCA2 mutations and triple-negative breast cancer. PLoS One 7:e38361

    Article  PubMed  CAS  Google Scholar 

  20. Lakhani SR, Reis-Filho JS, Fulford L et al (2005) Prediction of BRCA1 status in patients with breast cancer using estrogen receptor and basal phenotype. Clin Cancer Res 11:5175–5180

    Article  PubMed  CAS  Google Scholar 

  21. Foulkes WD, Stefansson IM, Chappuis PO, Begin LR, Goffin JR, Wong N, Trudel M, Akslen LA (2003) Germline BRCA1 mutations and a basal epithelial phenotype in breast cancer. J Natl Cancer Inst 95:1482–1485

    Article  PubMed  CAS  Google Scholar 

  22. Young SR, Pilarski RT, Donenberg T, Shapiro C, Hammond LS, Miller J, Brooks KA, Cohen S, Tenenholz B, Desai D, Zandvakili I, Royer R, Li S, Narod SA (2009) The prevalence of BRCA1 mutations among young women with triple-negative breast cancer. BMC Cancer 9:86

    Article  PubMed  CAS  Google Scholar 

  23. Bertucci F, Finetti P, Cervera N, Esterni B, Hermitte F, Viens P, Birnbaum D (2008) How basal are triple-negative breast cancers? Int J Cancer 123:236–240

    Article  PubMed  CAS  Google Scholar 

  24. Turner N, Tutt A, Ashworth A (2004) Hallmarks of ‘BRCAness’ in sporadic cancers. Nat Rev Cancer 4:814–819

    Article  PubMed  CAS  Google Scholar 

  25. Moynahan ME, Cui TY, Jasin M (2001) Homology-directed DNA repair, mitomycin-c resistance, and chromosome stability is restored with correction of a Brca1 mutation. Cancer Res 61:4842–4850

    PubMed  CAS  Google Scholar 

  26. Michalak EM, Jonkers J (2011) Studying therapy response and resistance in mouse models for BRCA1-deficient breast cancer. J Mammary Gland Biol Neoplasia 16:41–50

    Article  PubMed  Google Scholar 

  27. Kennedy RD, Quinn JE, Mullan PB, Johnston PG, Harkin DP (2004) The role of BRCA1 in the cellular response to chemotherapy. J Natl Cancer Inst 96:1659–1668

    Article  PubMed  CAS  Google Scholar 

  28. Silver DP, Richardson AL, Eklund AC et al (2010) Efficacy of neoadjuvant Cisplatin in triple-negative breast cancer. Journal of Clin Oncol 28:1145–1153

    Article  CAS  Google Scholar 

  29. Moiseyenko VM, Protsenko SA, Brezhnev NV et al (2010) High sensitivity of BRCA1-associated tumors to cisplatin monotherapy: report of two cases. Cancer Genet Cytogenet 197:91–94

    Article  PubMed  CAS  Google Scholar 

  30. Rhiem K, Wappenschmidt B, Bosse K, Koppler H, Tutt AN, Schmutzler RK (2009) Platinum sensitivity in a BRCA1 mutation carrier with advanced breast cancer. Clin Oncol (R Coll Radiol) 21:448–450

    Article  CAS  Google Scholar 

  31. Isakoff J, Goss PE, Mayer EL et al (2010) TBCRC009: a multicenter phase II study of cisplatin or carboplatin for metastatic triple-negative breast cancer and evaluation of p63/p73 as a biomarker of response. J Clin Oncol 29(Suppl): Abstract 1025

    Google Scholar 

  32. Chadderton A, Villeneuve DJ, Gluck S et al (2000) Role of specific apoptotic pathways in the restoration of paclitaxel-induced apoptosis by valspodar in doxorubicin-resistant MCF-7 breast cancer cells. Breast Cancer Res Treat 59:231–244

    Article  PubMed  CAS  Google Scholar 

  33. Harkin DP, Bean JM, Miklos D (1999) Induction of GADD45 and JNK/SAPK-dependent apoptosis following inducible expression of BRCA1. Cell 97:575–586

    Article  PubMed  CAS  Google Scholar 

  34. Tassone P, Tagliaferri P, Perricelli A, Blotta S, Quaresima B, Martelli ML, Goel A, Barbieri V, Costanzo F, Boland CR, Venuta S (2003) BRCA1 expression modulates chemosensitivity of BRCA1-defective HCC1937 human breast cancer cells. Br J Cancer 88:1285–1291

    Article  PubMed  CAS  Google Scholar 

  35. Chabalier C, Lamare C, Racca C, Privat M, Valette A, Larminat F (2006) BRCA1 downregulation leads to premature inactivation of spindle checkpoint and confers paclitaxel resistance. Cell Cycle 5:1001–1007

    Article  PubMed  CAS  Google Scholar 

  36. Kriege M, Jager A, Hooning MJ et al (2012) The efficacy of taxane chemotherapy for metastatic breast cancer in BRCA1 and BRCA2 mutation carriers. Cancer 118:899–907

    Article  PubMed  CAS  Google Scholar 

  37. Wysocki PJ, Korski K, Lamperska K, Zaluski J, Mackiewicz A (2008) Primary resistance to docetaxel-based chemotherapy in metastatic breast cancer patients correlates with a high frequency of BRCA1 mutations. Med Sci Monit 14:7–10

    Google Scholar 

  38. Delaloge S, Pautier P, Kloos I et al (2002) BRCA1-linked breast cancer (BC) is highly more chemosensitive than its BRCA2-linked or sporadic counterparts. In: Presented at the 27th Congress of the European Society for Medical Oncology, October 18–22, 2002, Nice, France

  39. Chappuis PO, Goffin J, Wong N, Perret C, Ghadirian P, Tonin PN, Foulkes WD (2002) A significant response to neoadjuvant chemotherapy in BRCA1/2 related breast cancer. J Med Genet 39:608–610

    Article  PubMed  CAS  Google Scholar 

  40. Petit T, Wilt M, Rodier J, Muller D, Ghnassia J, Dufour P, Fricker J (2007) Are BRCA1 mutations a predictive factor for anthracycline-based neoadjuvant chemotherapy response in triple-negative breast cancers? J Clin Oncol 25(Supp l): Abstract 580

  41. Delaloge S, Bidard F, El Masmoudi Y et al (2008) BRCA1 germ-line mutation: Predictive of sensitivity to anthracyclin alkylating agents regimens but not to taxanes. J Clin Oncol 26(Suppl): Abstract 574

    Google Scholar 

  42. Kriege M, Seynaeve C, Meijers-Heijboer H et al (2009) Sensitivity to first-line chemotherapy for metastatic breast cancer in BRCA1 and BRCA2 mutation carriers. Journal of Clinical Oncology 27:3764–3771

    Article  PubMed  Google Scholar 

  43. Raphael J, Caron O, Rimareix F, Spielmann M et al (2011) BRCA2 mutation carriers respond poorly to conventional anthracylins/taxanes-based neo-adjuvant chemotherapy. In: San Antonio Breast Cancer Symposium, San Antonio, TX

  44. Fedier A, Steiner RA, Schwarz VA, Lenherr L, Haller U, Fink D (2003) The effect of loss of Brca1 on the sensitivity to anticancer agents in p53-deficient cells. Int J Oncol 22:1169–1173

    PubMed  CAS  Google Scholar 

  45. Evers B, Drost R, Schut E, de Bruin M, van der Burg E, Derksen PW, Holstege H, Liu X, van Drunen E, Beverloo HB, Smith GC, Martin NM, Lau A, O’Connor MJ, Jonkers J (2008) Selective inhibition of BRCA2-deficient mammary tumor cell growth by AZD2281 and cisplatin. Clin Cancer Res 14:3916–3925

    Article  PubMed  CAS  Google Scholar 

  46. Issaeva N, Thomas HD, Djureinovic T et al (2010) 6-thioguanine selectively kills BRCA2-defective tumors and overcomes PARP inhibitor resistance. Cancer Res 70:6268–6276

    Article  PubMed  CAS  Google Scholar 

  47. Donawho CK, Luo Y, Penning TD et al (2007) ABT-888, an orally active poly(ADP-ribose) polymerase inhibitor that potentiates DNA-damaging agents in preclinical tumor models. Clinical Cancer Research 13:2728–2737

    Article  PubMed  CAS  Google Scholar 

  48. Evers B, Schut E, van der Burg E, Braumuller TM, Egan DA, Holstege H, Edser P, Adams DJ, Wade-Martins R, Bouwman P, Jonkers J (2010) A high-throughput pharmaceutical screen identifies compounds with specific toxicity against BRCA2-deficient tumors. Clinical Cancer Research 16:99–108

    Article  PubMed  CAS  Google Scholar 

  49. Dhillon KK, Swisher EM, Taniguchi T (2011) Secondary mutations of BRCA1/2 and drug resistance. Cancer Sci 102:663–669

    Article  PubMed  CAS  Google Scholar 

  50. Huang SC, Wu ET, Wang CC, Chen YS, Chang CI, Chiu IS, Ko WJ, Wang SS (2012) Eleven years of experience with extracorporeal cardiopulmonary resuscitation for paediatric patients with in-hospital cardiac arrest. Resuscitation 83:710–714

    Article  PubMed  Google Scholar 

  51. Vollebergh MA, Nederlof P, Wessels LF et al (2009) Predicting response to alkylating chemotherapy in breast cancer patients using array comparative genomic hybridization. Cancer Res 69(Suppl 1): Abstract 6050

    Google Scholar 

  52. Mehta RS, Liu C et al (2011) Clinical outcome of triple-negative breast cancer with BRCA mutation in the context of dose-dense and or metronomic chemotherapy. J Clin Oncol 29(Suppl): Abstract 1109

    Google Scholar 

  53. Helleday T, Petermann E, Lundin C, Hodgson B, Sharma RA (2008) DNA repair pathways as targets for cancer therapy. Nat Rev Cancer 8:193–204

    Article  PubMed  CAS  Google Scholar 

  54. McCabe N, Turner NC, Lord CJ, Kluzek K, Bialkowska A, Swift S, Giavara S, O’Connor MJ, Tutt AN, Zdzienicka MZ, Smith GC, Ashworth A (2006) Deficiency in the repair of DNA damage by homologous recombination and sensitivity to poly(ADP-ribose) polymerase inhibition. Cancer Res 66:8109–8115

    Article  PubMed  CAS  Google Scholar 

  55. Ashworth A (2008) A synthetic lethal therapeutic approach: poly(ADP) ribose polymerase inhibitors for the treatment of cancers deficient in DNA double-strand break repair. J Clin Oncol 26:3785–3790

    Article  PubMed  CAS  Google Scholar 

  56. Farmer H, McCabe N, Lord CJ, Tutt AN, Johnson DA, Richardson TB, Santarosa M, Dillon KJ, Hickson I, Knights C, Martin NM, Jackson SP, Smith GC, Ashworth A (2005) Targeting the DNA repair defect in BRCA mutant cells as a therapeutic strategy. Nature 434:917–921

    Article  PubMed  CAS  Google Scholar 

  57. Bryant HE, Schultz N, Thomas HD, Parker KM, Flower D, Lopez E, Kyle S, Meuth M, Curtin NJ, Helleday T (2005) Specific killing of BRCA2-deficient tumours with inhibitors of poly(ADP-ribose) polymerase. Nature 434:913–917

    Article  PubMed  CAS  Google Scholar 

  58. Tutt A, Robson M, Garber JE, Domchek SM, Audeh MW, Weitzel JN, Friedlander M, Arun B, Loman N, Schmutzler RK, Wardley A, Mitchell G, Earl H, Wickens M, Carmichael J (2010) Oral poly(ADP-ribose) polymerase inhibitor olaparib in patients with BRCA1 or BRCA2 mutations and advanced breast cancer: a proof-of-concept trial. Lancet 376:235–244

    Article  PubMed  CAS  Google Scholar 

  59. O’Shaughnessy J, Osborne C, Pippen JE, Yoffe M, Patt D, Rocha C, Koo IC, Sherman BM, Bradley C (2011) Iniparib plus chemotherapy in metastatic triple-negative breast cancer. New Engl J Med 364:205–214

    Article  PubMed  Google Scholar 

  60. O’Shaughnessy J, Schwartzberg LS, Danso MA (2011) A randomized phase III study of iniparib (BSI-201) in combination with gemcitabine/carboplatin (G/C) in metastatic triple-negative breast cancer (TNBC). J Clin Oncol 29(Suppl): Abstract 1007

    Google Scholar 

  61. Rios J, Puhalla S (2011) PARP inhibitors in breast cancer: BRCA and beyond. Oncology 25:1014–1025

    PubMed  Google Scholar 

  62. Saal LH, Gruvberger-Saal SK, Persson C et al (2008) Recurrent gross mutations of the PTEN tumor suppressor gene in breast cancers with deficient DSB repair. Nat Genet 40:102–107

    Article  PubMed  CAS  Google Scholar 

  63. Kimbung S, Biskup E, Johansson I, Aaltonen K, Ottosson-Wadlund A, Gruvberger-Saal S, Cunliffe H, Fadeel B, Loman N, Berglund P, Hedenfalk I (2012) Co-targeting of the PI3K pathway improves the response of BRCA1 deficient breast cancer cells to PARP1 inhibition. Cancer Lett 319:232–241

    Article  PubMed  CAS  Google Scholar 

  64. Kim MS, Blake M, Baek JH, Kohlhagen G, Pommier Y, Carrier F (2003) Inhibition of histone deacetylase increases cytotoxicity to anticancer drugs targeting DNA. Cancer Res 63:7291–7300

    PubMed  CAS  Google Scholar 

  65. Weberpals JI OBA, Garbuio K et al (2009) Investigation of HDAC inhibition targeting of BRCA1 expression as a mechanism to enhance platinum sensitivity in breast and ovarian cancer. J Clin Oncol 27(Suppl): Abstract e22017

  66. Gronwald J, Tung N, Foulkes WD et al (2006) Tamoxifen and contralateral breast cancer in BRCA1 and BRCA2 carriers: an update. Int J Cancer J Int Cancer 118:2281–2284

    Article  CAS  Google Scholar 

  67. Phillips KA (2011) Tamoxifen may reduce contralateral cancers in BRCA mutation carriers. J Clin Oncol, Abstract 1500

  68. Wesolowski R, Moore SA, Tao J, Harris RC (2009) Differential outcomes in patients treated with endocrine therapy for early or locally advanced breast cancer based on BRCA mutation status. J Clin Oncol 27(suppl): Abstract e22065

  69. Egawa C, Motomura K, Miyoshi Y, Takamura Y, Taguchi T, Tamaki Y, Inaji H, Koyama H, Noguchi S (2003) Increased expression of BRCA1 mRNA predicts favorable response to anthracycline-containing chemotherapy in breast cancers. Breast Cancer Res Treat 78:45–50

    Article  PubMed  CAS  Google Scholar 

  70. Collins C, Huo D, Xu J et al (2007) Relationship between BRCA1 promoter methylation and sensitivity of breast cancer cell lines to cisplatin and paclitaxel. J Clin Oncol. In: 2007 ASCO annual meeting proceedings part I, vol 25, No. 18S

  71. Isakoff SJ, Overmayer B, Tung NM, Gelman RS et al (2010) A phase II trial of the PARP inhibitor veliparib (ABT888) and temozolomide for metastatic breast cancer. J Clin Oncol 28:15s

    Google Scholar 

  72. Tan AR, Toppmeyer D, Stein MN et al (2011) 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 29(suppl): Abstract 3041

    Google Scholar 

  73. Sharma P, Kimler BF, Park YA et al (2011) Association of BRCA1 promoter methylation in triple-negative breast cancer (TNBC) with resistance to standard anthracyline-based adjuvant chemotherapy. J Clin Oncol 29(Suppl): Abstract 1123

    Google Scholar 

  74. Rodriguez AA, Makris A, Wu MF, Rimawi M, Froehlich A, Dave B, Hilsenbeck SG, Chamness GC, Lewis MT, Dobrolecki LE, Jain D, Sahoo S, Osborne CK, Chang JC (2010) DNA repair signature is associated with anthracycline response in triple negative breast cancer patients. Breast Cancer Res Treat 123:189–196

    Article  PubMed  CAS  Google Scholar 

  75. Kurebayashi J, Yamamoto Y, Kurosumi M, Okubo S, Nomura T, Tanaka K, Sonoo H (2006) Loss of BRCA1 expression may predict shorter time-to-progression in metastatic breast cancer patients treated with taxanes. Anticancer Res 26:695–701

    PubMed  CAS  Google Scholar 

  76. Warner E, Trudeau M, Holloway C (2003) Sensitivity of BRCA-1-related breast cancer to neoadjuvant chemotherapy: practical implications. Breast J 9:507–508

    Article  PubMed  Google Scholar 

  77. Hubert A, Mali B, Hamburger T, Rottenberg Y, Uziely B, Peretz T, Kadouri L (2009) Response to neo-adjuvant chemotherapy in BRCA1 and BRCA2 related stage III breast cancer. Fam Cancer 8:173–177

    Article  PubMed  CAS  Google Scholar 

  78. Fourquet A, Stoppa-Lyonnet D, Kirova YM, Sigal-Zafrani B, Asselain B (2009) Familial breast cancer: clinical response to induction chemotherapy or radiotherapy related to BRCA1/2 mutations status. Am J Clin Oncol 32:127–131

    Article  PubMed  CAS  Google Scholar 

  79. Melichar B, Fridrichova P, Lukesova S, Mergancova J, Urminska H, Ryska A, Foretova L (2008) Pathological complete response after primary chemotherapy in a mother and daughter with hereditary breast carcinoma: two case reports. Eur J Gynaecol Oncol 29:188–190

    PubMed  CAS  Google Scholar 

  80. Lee J, Annunziate C, Minasian LM et al (2011) Phase I study of the PARP inhibitor olaparib (O) in combination with carboplatin (C) in BRCA1/2 mutation carriers with breast (Br) or ovarian (Ov) cancer (Ca). J Clin Oncol 29(suppl): Abstract 2520

    Google Scholar 

  81. Liu J FG, Tolaney SM et al (2011) A phase I trial of the PARP inhibitor olaparib (AZD2281) in combination with the antiangiogenic cediranib (AZD2171) in recurrent ovarian or triple-negative breast cancer. J Clin Oncol 29(Suppl): Abstract 5028

    Google Scholar 

  82. Moulder S, Mita M, Bradley C, Rocha C, Harris L (2010) A phase 1b study to assess the safety and tolerability of the PARP inhibitor Iniparib (BSI-201) in combination with Irinotecan for the treatment of patients with metastatic breast cancer. In: San Antonio breast cancer symposium. Cancer Research, San Antonio, TX, 70(24), Suppl 2

  83. Kummar S, Ji J, Morgan R et al (2012) A phase I study of veliparib in combination with metronomic cyclophosphamide in adults with refractory solid tumors and lymphomas. Clin Cancer Res 18:1726–1734

    Article  PubMed  CAS  Google Scholar 

  84. Somlo G, Van Laere SJ, Cigler T et al (2012) ABT-888 (veliparib) in combination with carboplatin in patients with stage IV BRCA-associated breast cancer. A California Cancer Consortium Trial. J Clin Oncol, Abstract 1010

  85. Gelmon KA, Hirte H, Robidoux A et al (2010) Can we define tumors that will respond to PARP inhibitors? A phase II correlative study of olaparib in advanced serous ovarian cancer and triple-negative breast cancer. J Clin Oncol 28:15s, Abstract 3002

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  1. Department of Medicine, Division of Hematology/Medical Oncology, University of Miami and Sylvester Comprehensive Cancer Center, Miami, FL, USA

    Soley Bayraktar & Stefan Glück

  2. Sylvester Comprehensive Cancer Center, Leonard L. Miller School of Medicine, University of Miami, 1475 NW 12th Ave St 3300, Miami, FL, 33136, USA

    Stefan Glück

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Bayraktar, S., Glück, S. Systemic therapy options in BRCA mutation-associated breast cancer. Breast Cancer Res Treat 135, 355–366 (2012). https://doi.org/10.1007/s10549-012-2158-6

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