BRCA 1/2-mutation related and sporadic breast and ovarian cancersmore alike than different

Frontiers in Oncology

Volumn 4 MAR, Issue , 2014, Pages

  Burgess, Melissa ^a   Puhalla, Shannon ^a  

^a UNIVERSITY OF PITTSBURGH MEDICAL CENTER   (United States)

Author keywords

BRCA 1 2 mutations; Brcaness; Breast cancer; Ovarian cancer; PARP inhibitor; Reversion mutations

Indexed keywords

ANTINEOPLASTIC AGENT; BMN 673; BUPARLISIB; CAPECITABINE; CARBOPLATIN; CEDIRANIB; CISPLATIN; CO 338; CYCLOPHOSPHAMIDE; DOXORUBICIN; ERIBULIN; FLOXURIDINE; GEMCITABINE; INIPARIB; NAVELBINE; NICOTINAMIDE ADENINE DINUCLEOTIDE ADENOSINE DIPHOSPHATE RIBOSYLTRANSFERASE INHIBITOR; NIRAPARIB; OLAPARIB; PACLITAXEL; PLACEBO; PLATINUM; RUCAPARIB; TAXANE DERIVATIVE; TEMOZOLOMIDE; TOPOTECAN; UNCLASSIFIED DRUG; VELIPARIB;

ALOPECIA; ANEMIA; ANOREXIA; BREAST CANCER; CONSTIPATION; DNA DAMAGE; DNA REPAIR; DRUG DOSE ESCALATION; DRUG DOSE REDUCTION; EPIGENETICS; FATIGUE; FLATULENCE; GENE MUTATION; GENOMIC INSTABILITY; GENOTYPE PHENOTYPE CORRELATION; HEMATOLOGIC DISEASE; HISTOLOGY; HUMAN; HYPERSENSITIVITY; HYPERTENSION; MICROARRAY ANALYSIS; MULTIPLE CYCLE TREATMENT; NAUSEA; NAUSEA AND VOMITING; NEUTROPENIA; OVARY CANCER; PHASE 1 CLINICAL TRIAL (TOPIC); PHASE 2 CLINICAL TRIAL (TOPIC); PHASE 3 CLINICAL TRIAL (TOPIC); PNEUMONIA; PROTEIN EXPRESSION; RECOMMENDED DRUG DOSE; REVIEW; SIGNAL TRANSDUCTION; SOMATIC MUTATION; THROMBOCYTOPENIA;

EID: 84898490259     PISSN: None     EISSN: 2234943X     Source Type: Journal    
DOI: 10.3389/fonc.2014.00019     Document Type: Review

References (109)

1. D'Andrea AD, Grompe M. The Fanconi anaemia/BRCA pathway. Nat Rev Cancer (2003) 3:23-34. doi: 10.1038/nrc970
2. ElKhamisy SF, Masutani M, Suzuki H, Caldecott KW. A requirement for PARP-1 for the assembly or stability of XRCC1 nuclear foci at sites of oxidative DNA damage. Nucleic Acids Res (2003) 31(19):5526-33. doi:10.1093/nar/gkg761
3. Satoh MS, Lindahl T. Role of poly(ADPribose) formation in DNA repair. Nature (1992) 356:356-8. doi:10.1038/356356a0
4. Masson M, Niedergang C, Schreiber V, Muller S, Menissierde Murcia J, de Murcia G. XRCC1 is specifically associated with poly(ADPribose) polymerase and negatively regulates its activity following DNA damage. Mol Cell Biol (1998) 18(6):3563-71.
5. Strom CE, Johansson F, Uhlen M, Szigyarto CA, Erixon K, Helleday T. Poly (ADPribose) polymerase (PARP) is not involved in base excision repair but PARP inhibition traps a singlestrand intermediate. Nucleic Acids Res (2011) 39(8):3166-75. doi:10.1093/nar/gkq1241
6. Ashworth A. A synthetic lethal therapeutic approach: poly (ADP) ribose polymerase inhibitors for the treatment of cancers deficient in DNA doublestrand break repair. J Clin Oncol (2008) 26:3785-90. doi:10.1200/JCO.2008.16.0812
7. Hoeijmakers JH. Genome maintenance mechanisms for preventing cancer. Nature (2001) 411:366-74. doi:10.1038/35077232
8. Dobzhansky T. Genetics of natural populations; recombination and variability in populations of Drosophila pseudoobscura. Genetics (1946) 31:269-90.
9. De Lorenzo SB, Patel AG, Hurley RM, Kaufmann SH. The elephant and the blind men: making sense of PARP inhibitors in homologous recombination deficient tumor cells. Front Oncol (2013) 3:228. doi:10.3389/fonc.2013.00228
10. American Cancer Society. Cancer Facts & Figures 2013. Atlanta: American Cancer Society (2013).
11. Alsop K, Fereday S, Meldrum C, deFazio A, Emmanuel C, George J, et al. BRCA mutation frequency and patterns of treatment response in BRCA mutationpositive women with ovarian cancer: a report from the Australian Ovarian Cancer Study Group. J Clin Oncol (2012) 30(21):2654-63. doi:10.1200/JCO.2011.39.8545
12. Cass I, Baldwin RL, Varkey T, Moslehi R, Narod SA, Karlan BY. Improved survival in women with BRCAassociated ovarian carcinoma. Cancer (2003) 97(9):2187-95. doi:10.1002/cncr.11310
13. Ben David Y, Chetrit A, HirshYechezkel G, Friedman E, Beck BD, Beller U, et al. Effect of BRCA mutations on the length of survival in epithelial ovarian tumors. J Clin Oncol (2002) 20(2):463-6. doi:10.1200/JCO.20.2.463
14. Boyd J, Sonoda Y, Federici MG, Bogomolniy F, Rhei E, Maresco DL, et al. Clinicopathologic features of BRCAlinked and sporadic ovarian cancer. JAMA (2000) 283(17):2260-5. doi:10.1001/jama.283.17.2260
15. Chetrit A, HirshYechezkel G, BenDavid Y, Lubin F, Friedman E, Sadetzki S. Effect of BRCA1/2 mutations on longterm survival of patients with invasive ovarian cancer: the national Israeli study of ovarian cancer. J Clin Oncol (2008) 26(1):20-5. doi:10.1200/JCO.2007.11.6905
16. Rubin SC, Benjamin I, Behbakht K, Takahashi H, Morgan MA, LiVolsi VA, et al. Clinical and pathological features of ovarian cancer in women with germline mutations of BRCA1. N Engl J Med (1996) 335(19):1413-6. doi:10.1056/NEJM199611073351901
17. Brekelmans CT, Seynaeve C, MenkePluymers M, Brüggenwirth HT, TilanusLinthorst MM, Bartels CC, et al. Survival and prognostic factors in BRCA1-associated breast cancer. Ann Oncol (2006) 17(3):391-400. doi:10.1093/annonc/mdj095
18. Arnes JB, Brunet JS, Stefansson I, Bégin LR, Wong N, Chappuis PO, et al. Placental cadherin and the basal epithelial phenotype of BRCA1-related breast cancer. Clin Cancer Res (2005) 11(11):4003-11. doi:10.1158/1078-0432.CCR-04-2064
19. Foulkes WD, Brunet JS, Stefansson IM, Straume O, Chappuis PO, Bégin LR, et al. The prognostic implication of the basallike (cyclin E high/p27 low/p53+/glomeruloidmicrovascular-proliferation+) phenotype of BRCA1-related breast cancer. Cancer Res (2004) 64(3):830-5. doi:10.1158/0008-5472.CAN-03-2970
20. Foulkes WD, Stefansson IM, Chappuis PO, Bégin LR, Goffin JR, Wong N, et al. Germline BRCA1 mutations and a basal epithelial phenotype in breast cancer. J Natl Cancer Inst (2003) 95(19):1482-5. doi:10.1093/jnci/djg050
21. Laakso M, Loman N, Borg A, Isola J. Cytokeratin 5/14-positive breast cancer: true basal phenotype confined to BRCA1 tumors. Mod Pathol (2005) 18(10):1321-8. doi:10.1038/modpathol.3800456
22. Lakhani SR, Van De Vijver MJ, Jacquemier J, Anderson TJ, Osin PP, McGuffog L, et al. The pathology of familial breast cancer: predictive value of immunohistochemical markers estrogen receptor, progesterone receptor, HER-2, and p53 in patients with mutations in BRCA1 and BRCA2. J Clin Oncol (2002) 20(9):2310-8. doi:10.1200/JCO.2002.09.023
23. Palacios J, Honrado E, Osorio A, Cazorla A, Sarrió D, Barroso A, et al. Immunohistochemical characteristics defined by tissue microarray of hereditary breast cancer not attributable to BRCA1 or BRCA2 mutations: differences from breast carcinomas arising in BRCA1 and BRCA2 mutation carriers. Clin Cancer Res (2003) 9(10 Pt 1):3606-14.
24. Rakha EA, ReisFilho JS, Ellis IO. Basallike breast cancer: a critical review. J Clin Oncol (2008) 26(15):2568-81. doi:10.1200/JCO.2007.13.1748
25. Sorlie T, Tibshirani R, Parker J, Hastie T, Marron JS, Nobel A, et al. Repeated observation of breast tumor subtypes in independent gene expression data sets. Proc Natl Acad Sci U S A (2003) 100(14):8418-23. doi:10.1073/pnas.0932692100
26. Turner N, Tutt A, Ashworth A. Hallmarks of "BRCAness" in sporadic cancers. Nat Rev Cancer (2004) 4(10):814-9. doi:10.1038/nrc1457
27. Silver DP, Richardson AL, Eklund AC, Wang ZC, Szallasi Z, Li Q, et al. Efficacy of neoadjuvant cisplatin in triplenegative breast cancer. J Clin Oncol (2010) 28(7):1145-53. doi:10.1200/JCO.2009.22.4725
28. Byrski T, Gronwald J, Huzarski T, Grzybowska E, Budryk M, Stawicka M, et al. Pathologic complete response rates in young women with BRCA1-positive breast cancers after neoadjuvant chemotherapy. J Clin Oncol (2010) 28(3):375-9. doi:10.1200/JCO.2008.20.7019
29. Park Y, Moriyama A, Kitahara T, Yoshida Y, Urita T, Kato R. Triplenegative breast cancer and poly(ADPribose) polymerase inhibitors. Anticancer Agents Med Chem (2012) 12(6):672-7. doi:10.2174/187152012800617759
30. Lehmann BD, Bauer JA, Chen X, Sanders ME, Chakravarthy AB, Shyr Y, et al. Identification of human triplenegative breast cancer subtypes and preclinical models for selection of targeted therapies. J Clin Invest (2011) 121(7):2750-67. doi:10.1172/JCI45014
31. Masuda H, Baggerly KA, Wang Y, Zhang Y, GonzalezAngulo AM, MericBernstam F, et al. Differential pathologic complete response rates after neoadjuvant chemotherapy among molecular subtypes of triplenegative breast cancer. J Clin Oncol (2013) 31(Suppl):abstr 1005.
32. Telli ML, Jensen KC, Kurian AW, Vinayak S, Lipson JA, Schackmann EA, et al. PrECOG 0105: final efficacy results from a phase II study of gemcitabine (G) and carboplatin (C) plus iniparib (BSI-201) as neoadjuvant therapy for triplenegative (TN) and BRCA 1/2 mutationassociated breast cancer. J Clin Oncol (2013) 31(Suppl):abstr 1003.
33. Abkevich V, Timms KM, Hennessy BT, Potter J, Carey MS, Meyer LA, et al. Patterns of genomic loss of heterozygosity predict homologous recombination repair defects in epithelial ovarian cancer. Br J Cancer (2012) 107(10):1776-82. doi:10.1038/bjc.2012.451
34. Turner NC, ReisFilho JS. Basallike breast cancer and the BRCA1 phenotype. Oncogene (2006) 25(43):5846-53. doi:10.1038/sj.onc.1209876
35. Turner NC, ReisFilho JS, Russell AM, Springall RJ, Ryder K, Steele D, et al. BRCA1 dysfunction in sporadic basallike breast cancer. Oncogene (2007) 26(14):2126-32. doi:10.1038/sj.onc.1210014
36. Yang Q, Sakurai T, Mori I, Yoshimura G, Nakamura M, Nakamura Y, et al. Prognostic significance of BRCA1 expression in Japanese sporadic breast carcinomas. Cancer (2001) 92(1):54-60. doi:10.1002/1097-0142(20010701)92:154::AIDCNCR1291>3.0.CO;2-8
37. Lips EH, Mulder L, Oonk A, van der Kolk LE, Hogervorst FB, Imholz AL, et al. Triplenegative breast cancer: BRCAness and concordance of clinical features with BRCA1-mutation carriers. Br J Cancer (2013) 108(10):2172-7. doi:10.1038/bjc.2013.144
38. Weberpals JI, ClarkKnowles KV, Vanderhyden BC. Sporadic epithelial ovarian cancer: clinical relevance of BRCA1 inhibition in the DNA damage and repair pathway. J Clin Oncol (2008) 26(19):3259-67. doi:10.1200/JCO.2007.11.3902
39. George J, Alsop K, Etemadmoghadam D, Hondow H, Mikeska T, Dobrovic A, et al. Nonequivalent gene expression and copy number alterations in highgrade serous ovarian cancers with BRCA1 and BRCA2 mutations. Clin Cancer Res (2013) 19(13):3474-84. doi:10.1158/1078-0432.CCR-13-0066
40. Hilton JL, Geisler JP, Rathe JA, HattermannZogg MA, DeYoung B, Buller RE. Inactivation of BRCA1 and BRCA2 in ovarian cancer. J Natl Cancer Inst (2002) 94(18):1396-406. doi:10.1093/jnci/94.18.1396
41. Baldwin RL, Nemeth E, Tran H, Shvartsman H, Cass I, Narod S, et al. BRCA1 promoter region hypermethylation in ovarian carcinoma: a populationbased study. Cancer Res (2000) 60(19):5329-33.
42. Catteau A, Harris WH, Xu CF, Solomon E. Methylation of the BRCA1 promoter region in sporadic breast and ovarian cancer: correlation with disease characteristics. Oncogene (1999) 18(11):1957-65. doi:10.1038/sj.onc.1202509
43. Chan KY, Ozcelik H, Cheung AN, Ngan HY, Khoo US. Epigenetic factors controlling the BRCA1 and BRCA2 genes in sporadic ovarian cancer. Cancer Res (2002) 62(14):4151-6.
44. Esteller M, Silva JM, Dominguez G, Bonilla F, MatiasGuiu X, Lerma E, et al. Promoter hypermethylation and BRCA1 inactivation in sporadic breast and ovarian tumors. J Natl Cancer Inst (2000) 92(7):564-9. doi:10.1093/jnci/92.7.564
45. Geisler JP, HattermanZogg MA, Rathe JA, Buller RE. Frequency of BRCA1 dysfunction in ovarian cancer. J Natl Cancer Inst (2002) 94(1):61-7. doi:10.1093/jnci/94.1.61
46. Rice JC, Ozcelik H, Maxeiner P, Andrulis I, Futscher BW. Methylation of the BRCA1 promoter is associated with decreased BRCA1 mRNA levels in clinical breast cancer specimens. Carcinogenesis (2000) 21(9):1761-5. doi:10.1093/carcin/21.9.1761
47. Berchuck A, Heron KA, Carney ME, Lancaster JM, Fraser EG, Vinson VL, et al. Frequency of germline and somatic BRCA1 mutations in ovarian cancer. Clin Cancer Res (1998) 4(10):2433-7.
48. Merajver SD, Frank TS, Xu J, Pham TM, Calzone KA, BennettBaker P, et al. Germline BRCA1 mutations and loss of the wildtype allele in tumors from families with early onset breast and ovarian cancer. Clin Cancer Res (1995) 1(5):539-44.
49. Smith SA, Easton DF, Evans DG, Ponder BA. Allele losses in the region 17q12-21 in familial breast and ovarian cancer involve the wildtype chromosome. Nat Genet (1992) 2(2):128-31. doi:10.1038/ng1092-128
50. Tong D, Kucera E, Schuster E, Schmutzler RK, Swoboda H, Reinthaller A, et al. Loss of heterozygosity (LOH) at p53 is correlated with LOH at BRCA1 and BRCA2 in various human malignant tumors. Int J Cancer (2000) 88(2):319-22. doi:10.1002/1097-0215(20001015)88:2319::AIDIJC27>3.0.CO;2-X
51. Werness BA, Parvatiyar P, Ramus SJ, Whittemore AS, GarlinghouseJones K, OakleyGirvan I, et al. Ovarian carcinoma in situ with germline BRCA1 mutation and loss of heterozygosity at BRCA1 and TP53. J Natl Cancer Inst (2000) 92(13):1088-91. doi:10.1093/jnci/92.13.1088
52. Collins N, Wooster R, Stratton MR. Absence of methylation of CpG dinucleotides within the promoter of the breast cancer susceptibility gene BRCA2 in normal tissues and in breast and ovarian cancers. Br J Cancer (1997) 76(9):1150-6. doi:10.1038/bjc.1997.526
53. Hennessy BT, Timms KM, Carey MS, Gutin A, Meyer LA, Flake DD II, et al. Somatic mutations in BRCA1 and BRCA2 could expand the number of patients that benefit from poly (ADP ribose) polymerase inhibitors in ovarian cancer. J Clin Oncol (2010) 28(22):3570-6. doi:10.1200/JCO.2009.27.2997
54. GonzalezAngulo AM, Timms KM, Liu S, Chen H, Litton JK, Potter J, et al. Incidence and outcome of BRCA mutations in unselected patients with triple receptornegative breast cancer. Clin Cancer Res (2011) 17(5):1082-9. doi:10.1158/1078-0432.CCR-10-2560..
55. Cancer Genome Atlas Network. Comprehensive molecular portraits of human breast tumours. Nature (2012) 490(7418):61-70. doi:10.1038/nature11412
56. Cancer Genome Atlas Research Network. Integrated genomic analyses of ovarian carcinoma. Nature (2011) 474(7353):609-15. doi:10.1038/nature10166
57. Crook T, Brooks LA, Crossland S, Osin P, Barker KT, Waller J, et al. p53 Mutation with frequent novel condons but not a mutator phenotype in BRCA1- and BRCA2-associated breast tumours. Oncogene (1998) 17(13):1681-9. doi:10.1038/sj.onc.1202106
58. Greenblatt MS, Chappuis PO, Bond JP, Hamel N, Foulkes WD. TP53 mutations in breast cancer associated with BRCA1 or BRCA2 germline mutations: distinctive spectrum and structural distribution. Cancer Res (2001) 61(10):4092-7.
59. Bryant HE, Schultz N, Thomas HD, Parker KM, Flower D, Lopez E, et al. Specific killing of BRCA2-deficient tumours with inhibitors of poly(ADPribose) polymerase. Nature (2005) 434(7035):913-7. doi:10.1038/nature03443
60. 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(7035):917-21. doi:10.1038/nature03445
61. 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(ADPribose) polymerase inhibition. Cancer Res (2006) 66(16):8109-15. doi:10.1158/0008-5472.CAN-06-0140
62. Fong PC, Boss DS, Yap TA, Tutt A, Wu P, MerguiRoelvink M, et al. Inhibition of poly(ADPribose) polymerase in tumors from BRCA mutation carriers. N Engl J Med (2009) 361(2):123-34. doi:10.1056/NEJMoa0900212
63. Audeh MW, Carmichael J, Penson RT, Friedlander M, Powell B, BellMcGuinn KM, et al. Oral poly(ADPribose) polymerase inhibitor olaparib in patients with BRCA1 or BRCA2 mutations and recurrent ovarian cancer: a proofof-concept trial. Lancet (2010) 376(9737):245-51. doi:10.1016/S0140-6736(10)60893-8
64. Tutt A, Robson M, Garber JE, Domchek SM, Audeh MW, Weitzel JN, et al. Oral poly(ADPribose) polymerase inhibitor olaparib in patients with BRCA1 or BRCA2 mutations and advanced breast cancer: a proofof-concept trial. Lancet (2010) 376(9737):235-44. doi:10.1016/S0140-6736(10)60892-6
65. Gelmon KA, Tischkowitz M, Mackay H, Swenerton K, Robidoux A, Tonkin K, et al. Olaparib in patients with recurrent highgrade serous or poorly differentiated ovarian carcinoma or triplenegative breast cancer: a phase 2, multicentre, openlabel, nonrandomised study. Lancet Oncol (2011) 12(9):852-61. doi:10.1016/S1470-2045(11)70214-5
66. Kaye SB, Lubinski J, Matulonis U, Ang JE, Gourley C, Karlan BY, et al. Phase II, openlabel, randomized, multicenter study comparing the efficacy and safety of olaparib, a poly (ADPribose) polymerase inhibitor, and pegylated liposomal doxorubicin in patients with BRCA1 or BRCA2 mutations and recurrent ovarian cancer. J Clin Oncol (2012) 30:372-9. doi:10.1200/JCO.2011.36.9215
67. Murai J, Huang SY, Das BB, Renaud A, Zhang Y, Doroshow JH, et al. Trapping of PARP1 and PARP2 by clinical PARP inhibitors. Cancer Res (2012) 72(21):5588-99. doi:10.1158/0008-5472.CAN-12-2753
68. Sandhu SK, Schelman WR, Wilding G, Moreno V, Baird RD, Miranda S, et al. The poly(ADPribose) polymerase inhibitor niraparib (MK4827) in BRCA mutation carriers and patients with sporadic cancer: a phase 1 doseescalation trial. Lancet Oncol (2013) 14(9):882-92. doi:10.1016/S1470-2045(13)70240-7
69. Kristeleit RS, Shapiro G. A phase I doseescalation and PK study of continuous oral rucaparib in patients with advanced solid tumors. J Clin Oncol (2013) 31(Suppl):abstr 2585.
70. Shen Y, Rehman FL, Feng Y, Boshuizen J, Bajrami I, Elliott R, et al. BMN 673, a novel and highly potent PARP1/2 inhibitor for the treatment of human cancers with DNA repair deficiency. Clin Cancer Res (2013) 19(18):5003-15. doi:10.1158/1078-0432.CCR-13-1391
71. De Bono JS, Mina LA, Gonzalez M, Curtin NJ, Wang E, Henshaw JW, et al. First inhuman trial of novel oral PARP inhibitor BMN 673 in patients with solid tumors. J Clin Oncol (2013) 31(Suppl):abstr 2580.
72. Lee J, Annunziata CM, Hays JL, Noonan AM, Minasian LM, Zujewski J, et al. Phase I/Ib study of the PARP inhibitor olaparib (O) with carboplatin (C) in BRCA1/2 mutation carriers with breast or ovarian cancer (Br/OvCa) (NCT00647062). J Clin Oncol (2013) 31(Suppl):abstr 2514.
73. O'Shaughnessy J, Osborne C, Pippen JE, Yoffe M, Patt D, Rocha C, et al. Iniparib plus chemotherapy in metastatic triplenegative breast cancer. N Engl J Med (2011) 364(3):205-14. doi:10.1056/NEJMoa1011418
74. O'Shaughnessy J, Schwartzberg LS, Danso MA, Rugo HS, Miller K, Yardley DA, et al. A randomized phase III study of iniparib (BSI-201) in combination with gemcitabine/carboplatin (G/C) in metastatic triplenegative breast cancer (TNBC). J Clin Oncol (2011) 29(15s):abstr 1007.
75. Ji J, Lee MP, Kadota M, Zhang Y, Parchment RE, Tomaszewski JE, et al. Pharmacodynamic and pathway analysis of three presumed inhibitors of poly (ADPribose) polymerase: ABT-888, AZD2281, and BSI201. In: Proceedings of the AACR 102nd Annual Meeting. Vol. 52. Orlando, FL (2011). 1080 p.
76. 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 secondline treatment of patients with metastatic triplenegative breast cancer. Breast Cancer Res (2013) 15(5):R88. doi:10.1186/bcr3484
77. Hayes DF, Thor AD, Dressler LG, Weaver D, Edgerton S, Cowan D, et al. HER2 and response to paclitaxel in nodepositive breast cancer. N Engl J Med (2007) 357:1496-506. doi:10.1056/NEJMoa071167
78. Martín M, RodríguezLescure A, Ruiz A, Alba E, Calvo L, RuizBorrego M, et al. Molecular predictors of efficacy of adjuvant weekly paclitaxel in early breast cancer. Breast Cancer Res Treat (2010) 123:149-57. doi:10.1007/s10549-009-0663-z
79. Sparano JA, Wang M, Martino S, Jones V, Perez EA, Saphner T, et al. Weekly paclitaxel in the adjuvant treatment of breast cancer. N Engl J Med (2008) 358:1663-71. doi:10.1056/NEJMoa0707056
80. Puhalla SL, Appleman LJ, Beumer JH, Tawbi H, Stoller RG, Owonikoko TK, et al. Two phase I trials exploring different dosing schedules of carboplatin (C), paclitaxel (P), and the polyadpribose polymerase (PARP) inhibitor, veliparib (ABT-888) (V) with activity in triple negative breast cancer (TNBC). Cancer Res (2012) 72(24 Suppl):abstr PD09-6. doi:10.1158/0008-5472.SABCS12-PD09-06
81. Ledermann J, Harter P, Gourley C, Friedlander M, Vergote I, Rustin G, et al. Olaparib maintenance therapy in platinumsensitive relapsed ovarian cancer. N Engl J Med (2012) 366:1382-92. doi:10.1056/NEJMoa1105535
82. Liu JF, Tolaney SM, Birrer M, Fleming GF, Buss MK, Dahlberg SE, et al. A phase 1 trial of the poly(ADPribose) polymerase inhibitor olaparib (AZD2281) in combination with the antiangiogenic cediranib (AZD2171) in recurrent epithelial ovarian or triplenegative breast cancer. Eur J Cancer (2013) 49(14):2972-8. doi:10.1016/j.ejca.2013.05.020
83. Konstantinopoulos PA, Spentzos D, Karlan BY, Taniguchi T, Fountzilas E, Francoeur N, et al. Gene expression profile of BRCAness that correlates with responsiveness to chemotherapy and with outcome in patients with epithelial ovarian cancer. J Clin Oncol (2010) 28(22):3555-61. doi:10.1200/JCO.2009.27.5719
84. Dhillon KK, Swisher EM, Taniguchi T. Secondary mutations of BRCA1/2 and drug resistance. Cancer Sci (2011) 102(4):663-9. doi:10.1111/j.1349-7006.2010.01840.x
85. Swisher EM, Sakai W, Karlan BY, Wurz K, Urban N, Taniguchi T. Secondary BRCA1 mutations in BRCA1-mutated ovarian carcinomas with platinum resistance. Cancer Res (2008) 68(8):2581-6. doi:10.1158/0008-5472.CAN-08-0088
86. Barber LJ, Sandhu S, Chen L, Campbell J, Kozarewa I, Fenwick K, et al. Secondary mutations in BRCA2 associated with clinical resistance to a PARP inhibitor. J Pathol (2013) 229(3):422-9. doi:10.1002/path.4140
87. Norquist B, Wurz KA, Pennil CC, Garcia R, Gross J, Sakai W, et al. Secondary somatic mutations restoring BRCA1/2 predict chemotherapy resistance in hereditary ovarian carcinomas. J Clin Oncol (2011) 29(22):3008-15. doi:10.1200/JCO.2010.34.2980
88. Ang JE, Gourley C, Powell CB, High H, ShapiraFrommer R, Castonguay V, et al. Efficacy of chemotherapy in BRCA 1/2 mutation carrier ovarian cancer in the setting of parp inhibitor resistance: a multiinstitutional study. Clin Cancer Res (2013) 19(19):5485-93. doi:10.1158/1078-0432.CCR-13-1262
89. Kaufman B, ShapiraFrommer R, Schmutzler RK. Olaparib monotherapy in patients with advanced cancer and a germline BRCA1/2 mutation: an openlabel phase II study. J Clin Oncol (2013) 31(Suppl):abstr 11024.
90. van der Noll R, Ang JE, Jager A, Marchetti S, MerguiRoelvink M, DeBono JS, et al. Phase I study of olaparib in combination with carboplatin and/or paclitaxel in patients with advanced solid tumors. J Clin Oncol (2013) 31(Suppl):abstr 2579.
91. HugginsPuhalla SL, Beumer JH, Appleman LJ, Tawbi HA, Stoller RG, Lin Y, et al. A phase I study of chronically dosed, singleagent veliparib (ABT-888) in patients (pts) with either BRCA 1/2-mutated cancer (BRCA+), platinumrefractory ovarian cancer, or basallike breast cancer (BRCAwt). J Clin Oncol (2012) 30(Suppl):abstr 3054.
92. Ramaswamy B, Zhang J, Hall N, Schregel K, Lustberg MB, Weslowski R, et al. NCI 8609: interim fluoro-3'-deoxythymidine (FLT) PET imaging findings from the phase I trial of PARP inhibitor veliparib (V) and carboplatin (C) in advanced breast cancer. J Clin Oncol (2013) 31(Suppl):abstr 1023.
93. Clark CC, Weitzel JN, O'Connor TR. Efficacy of the combination of ABT-888 (veliparib) and carboplatin in patients with BRCAassociated breast cancer. J Clin Oncol (2013) 31(Suppl):abstr 1024.
94. Rodler ET, Specht JM, Gadi VK, Kurland BF, Griffin MJ, Hammon JJ, et al. Phase I study of PARP inhibitor ABT-888 (veliparib) in combination with cisplatin and vinorelbine for patients with advanced triple negative breast cancer and/or BRCAmutation associated breast cancer. Cancer Res (2011) 71(24 Suppl):abstr P1-17-04. doi:10.1158/0008-5472.SABCS11-P1-17-04
95. Tan A, Toppmeyer D, Tsan Lai Wong S, Lin H, Gounder M, Moss RA, et al. Assessment of γH2AX levels in circulating tumor cells in patients treated with veliparib in combination with doxorubicin and cyclophosphamide in metastatic breast cancer. J Clin Oncol (2013) 31(Suppl):abstr 2582.
96. 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(Suppl):abstr 1019.
97. Kummar S, Oza AM, Fleming GF, Sullivan D, Gandara DR, Erlichman C, et al. Randomized trial of oral cyclophosphamide (C) with or without veliparib (V), an oral poly (ADPribose) polymerase (PARP) inhibitor, in patients with recurrent BRCApositive ovarian, or primary peritoneal or highgrade serous ovarian carcinoma. J Clin Oncol (2012) 30(Suppl):abstr 5020.
98. BellMcGuinn K, 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(Suppl):abstr 2584.
99. Lee J, Annunziata CM, Minasian LM, Zujewski J, Prindiville SA, Kotz HL, et al. 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 (2011) 29(Suppl):abstr 2520.
100. Balmana J, Tung NM, Isakoff SJ. Phase I, openlabel study of olaparib plus cisplatin in patients with advanced solid tumors. J Clin Oncol (2012) 30(Suppl):abstr 1009.
101. Kummar S, Ji J, Morgan R, Lenz HJ, Puhalla SL, Belani CP, et al. A phase I study of veliparib in combination with metronomic cyclophosphamide in adults with refractory solid tumors and lymphomas. Clin Cancer Res (2012) 18(6):1726-34. doi:10.1158/1078-0432.CCR-11-2821
102. 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(Suppl):abstr 3049.
103. Oza AM, Cibula D, Oaknin A, Poole CJ, Mathijssen RHJ, Sonke GS, et al. Olaparib plus paclitaxel plus carboplatin (P/C) followed by olaparib maintenance treatment in patients (pts) with platinumsensitive recurrent serous ovarian cancer (PSR SOC): a randomized, openlabel phase II study. J Clin Oncol (2012) 30(Suppl):abstr 5001.
104. Molife LR, Roxburgh R, 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(Suppl):abstr 2586.
105. Miller KD, Perkins SM, Badve SS, Sledge GW, Schneider BP. PARP inhibition after preoperative chemotherapy in patients with triplenegative breast cancer (TNBC) or known BRCA 1/2 mutations: Hoosier Oncology Group BRE09-146. Cancer Res (2011) 71(24 Suppl):abstr OT3-01-5. doi:10.1158/0008-5472.SABCS11-OT3-01-05
106. Isakoff SJ, Puhalla S, Shepherd SP. A randomized, phase 2 study of the poly (ADPribose) polymerase (PARP) inhibitor veliparib (ABT-888) in combination with temozolomide (TMZ) or in combination with carboplatin (C) and paclitaxel (P) versus placebo plus C/P in subjects with BRCA1 or BRCA2 mutation and metastatic breast cancer. Cancer Res (2012) 72(24 Suppl):abstr OT2-3-07. doi:10.1158/0008-5472.SABCS12-OT2-3-07
107. Coleman R, Sill M, Aghajanian C. 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 - a Gynecologic Oncology Group study. Gynecol Oncol (2013) 130(1):e168. doi:10.1016/j.ygyno.2013.04.465
108. Pothuri B, Muggia F, Sparano JA, Blank SV, Curtin JP, Chuang E, et al. Dosedependent pharmacokinetic (PK) interaction of pegylated liposomal doxorubicin (PLD) with escalating doses of veliparib in a phase I study. J Clin Oncol (2013) 31(Suppl):abstr 2591.
109. Avery T, Berger AC, Kovatich AJ, Rui H, Hyslop T, Mitchell EP, et al. An adaptive randomized phase II trial to determine pathologic complete response with the addition of carboplatin with and without ABT-888 to standard chemotherapy in the neoadjuvant treatment of triplenegative breast cancer. J Clin Oncol (2013) 31(Suppl):abstr TS1135.