Application of molecular findings to the diagnosis and management of breast disease: Recent advances and challenges

Human Pathology

Volumn 42, Issue 2, 2011, Pages 153-165

  Simpson, Peter T ^a   Vargas, Ana Cristina ^a   Al Ejeh, Fares ^b   Khanna, Kum Kum ^b   Chenevix Trench, Georgia ^b   Lakhani, Sunil R ^a,c  

^a UNIVERSITY OF QUEENSLAND   (Australia)

^b QIMR BERGHOFER MEDICAL RESEARCH INSTITUTE   (Australia)

^c ROYAL BRISBANE AND WOMEN'S HOSPITAL   (Australia)

Author keywords

Breast cancer; Cancer biology; DNA damage response; High throughput technologies; Molecular pathways; Transcriptomic and proteomic alterations

Indexed keywords

ANTHRACYCLINE; DOCETAXEL; DOXORUBICIN; NICOTINAMIDE ADENINE DINUCLEOTIDE ADENOSINE DIPHOSPHATE RIBOSYLTRANSFERASE INHIBITOR; TAXANE DERIVATIVE; TUMOR MARKER;

ARTICLE; BREAST CANCER; CANCER SCREENING; CANCER THERAPY; CENTROSOME; CHROMOSOME; COPY NUMBER VARIATION; DNA DAMAGE; DOUBLE STRANDED DNA BREAK; EXCISION REPAIR; FAMILIAL CANCER; GENE EXPRESSION PROFILING; GENE REPLICATION; GENETIC COUNSELING; HIGH THROUGHPUT SCREENING; HUMAN; LETHAL GENE; METASTASIS; MISMATCH REPAIR; MOLECULAR BIOLOGY; NONHUMAN; ONCOGENE; POINT MUTATION; RISK ASSESSMENT; SINGLE STRANDED DNA BREAK; THERAPY RESISTANCE;

BREAST NEOPLASMS; DNA DAMAGE; FEMALE; GENE EXPRESSION PROFILING; GENE EXPRESSION REGULATION, NEOPLASTIC; HIGH-THROUGHPUT NUCLEOTIDE SEQUENCING; HUMANS; PATHOLOGY, MOLECULAR; PROGNOSIS; TUMOR MARKERS, BIOLOGICAL;

EID: 78751575999     PISSN: 00468177     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.humpath.2010.07.008     Document Type: Article

References (172)

1. Simpson P.T., Reis-Filho J.S., and Gale T. Molecular evolution of breast cancer J Pathol 205 2005 248 254
2. Geyer F.C., Lopez-Garcia M.A., and Lambros M.B. Genetic characterisation of breast cancer and implications for clinical management J Cell Mol Med 2009 [Epub ahead of print]
3. Rakha E.A., Reis-Filho J.S., and Ellis I.O. Combinatorial biomarker expression in breast cancer Breast Cancer Res Treat 120 2010 293 308
4. Arriola E., Rodriguez-Pinilla S.M., and Lambros M.B. Topoisomerase II alpha amplification may predict benefit from adjuvant anthracyclines in HER2 positive early breast cancer Breast Cancer Res Treat 106 2007 181 189
5. Tanner M., Isola J., and Wiklund T. Topoisomerase IIalpha gene amplification predicts favorable treatment response to tailored and dose-escalated anthracycline-based adjuvant chemotherapy in HER-2/neu-amplified breast cancer: Scandinavian Breast Group Trial 9401 J Clin Oncol 24 2006 2428 2436
6. Cheang M.C., Chia S.K., and Voduc D. Ki67 index, HER2 status, and prognosis of patients with luminal B breast cancer J Natl Cancer Inst 101 2009 736 750
7. Viale G., Regan M.M., and Mastropasqua M.G. Predictive value of tumor Ki-67 expression in two randomized trials of adjuvant chemoendocrine therapy for node-negative breast cancer J Natl Cancer Inst 100 2008 207 212
8. Vincent-Salomon A., Rousseau A., and Jouve M. Proliferation markers predictive of the pathological response and disease outcome of patients with breast carcinomas treated by anthracycline-based preoperative chemotherapy Eur J Cancer 40 2004 1502 1508
9. Gauthier M.L., Berman H.K., and Miller C. Abrogated response to cellular stress identifies DCIS associated with subsequent tumor events and defines basal-like breast tumors Cancer Cell 12 2007 479 491
10. Kerlikowske K., Molinaro A.M., and Gauthier M.L. Biomarker expression and risk of subsequent tumors after initial ductal carcinoma in situ diagnosis J Natl Cancer Inst 102 2010 627 637
11. Harbeck N., Kates R.E., and Schmitt M. Urokinase-type plasminogen activator and its inhibitor type 1 predict disease outcome and therapy response in primary breast cancer Clin Breast Cancer 5 2004 348 352
12. Look M.P., van Putten W.L., and Duffy M.J. Pooled analysis of prognostic impact of urokinase-type plasminogen activator and its inhibitor PAI-1 in 8377 breast cancer patients J Natl Cancer Inst 94 2002 116 128
13. Cheang M.C., Voduc D., and Bajdik C. Basal-like breast cancer defined by five biomarkers has superior prognostic value than triple-negative phenotype Clin Cancer Res 14 2008 1368 1376
14. Sorlie T., Perou C.M., and Tibshirani R. Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications Proc Natl Acad Sci U S A 98 2001 10869 10874
15. Perou C.M., Sorlie T., and Eisen M.B. Molecular portraits of human breast tumours Nature 406 2000 747 752
16. Hu Z., Fan C., and Oh D.S. The molecular portraits of breast tumors are conserved across microarray platforms BMC Genomics 7 2006 96
17. Parker J.S., Mullins M., and Cheang M.C. Supervised risk predictor of breast cancer based on intrinsic subtypes J Clin Oncol 27 2009 1160 1167
18. Weigelt B., Mackay A., and A'Hern R. Breast cancer molecular profiling with single sample predictors: a retrospective analysis Lancet Oncol 11 2010 339 349
19. van 't Veer L.J., Dai H., and van de Vijver M.J. Gene expression profiling predicts clinical outcome of breast cancer Nature 415 2002 530 536
20. Buyse M., Loi S., and van't Veer L. Validation and clinical utility of a 70-gene prognostic signature for women with node-negative breast cancer J Natl Cancer Inst 98 2006 1183 1192
21. Paik S., Shak S., and Tang G. A multigene assay to predict recurrence of tamoxifen-treated, node-negative breast cancer N Engl J Med 351 2004 2817 2826
22. Ma X.J., Hilsenbeck S.G., and Wang W. The HOXB13:IL17BR expression index is a prognostic factor in early-stage breast cancer J Clin Oncol 24 2006 4611 4619
23. Ma X.J., Salunga R., and Dahiya S. A five-gene molecular grade index and HOXB13:IL17BR are complementary prognostic factors in early stage breast cancer Clin Cancer Res 14 2008 2601 2608
24. Ma X.J., Wang Z., and Ryan P.D. A two-gene expression ratio predicts clinical outcome in breast cancer patients treated with tamoxifen Cancer Cell 5 2004 607 616
25. Loi S., Haibe-Kains B., and Desmedt C. Definition of clinically distinct molecular subtypes in estrogen receptor-positive breast carcinomas through genomic grade J Clin Oncol 25 2007 1239 1246
26. Sotiriou C., Wirapati P., and Loi S. Gene expression profiling in breast cancer: understanding the molecular basis of histologic grade to improve prognosis J Natl Cancer Inst 98 2006 262 272
27. Huang E., Cheng S.H., and Dressman H. Gene expression predictors of breast cancer outcomes Lancet 361 2003 1590 1596
28. Bild A.H., Parker J.S., and Gustafson A.M. An integration of complementary strategies for gene-expression analysis to reveal novel therapeutic opportunities for breast cancer Breast Cancer Res 11 2009 R55
29. Gatza M.L., Lucas J.E., and Barry W.T. A pathway-based classification of human breast cancer Proc Natl Acad Sci U S A 107 2010 6994 6999
30. Bild A.H., Yao G., and Chang J.T. Oncogenic pathway signatures in human cancers as a guide to targeted therapies Nature 439 2006 353 357
31. Borst M.J., and Ingold J.A. Metastatic patterns of invasive lobular versus invasive ductal carcinoma of the breast Surgery 114 1993 637 641 discussion 641-632
32. Fulford L.G., Reis-Filho J.S., and Ryder K. Basal-like grade III invasive ductal carcinoma of the breast: patterns of metastasis and long-term survival Breast Cancer Res 9 2007 R4
33. Bos P.D., Zhang X.H., and Nadal C. Genes that mediate breast cancer metastasis to the brain Nature 459 2009 1005 1009
34. Minn A.J., Gupta G.P., and Siegel P.M. Genes that mediate breast cancer metastasis to lung Nature 436 2005 518 524
35. Minn A.J., Gupta G.P., and Padua D. Lung metastasis genes couple breast tumor size and metastatic spread Proc Natl Acad Sci U S A 104 2007 6740 6745
36. van de Vijver M.J., He Y.D., and van't Veer L.J. A gene-expression signature as a predictor of survival in breast cancer N Engl J Med 347 2002 1999 2009
37. Wang Y., Klijn J.G., and Zhang Y. Gene-expression profiles to predict distant metastasis of lymph-node-negative primary breast cancer Lancet 365 2005 671 679
38. Chuang H.Y., Lee E., and Liu Y.T. Network-based classification of breast cancer metastasis Mol Syst Biol 3 2007 140
39. Weigelt B., Hu Z., and He X. Molecular portraits and 70-gene prognosis signature are preserved throughout the metastatic process of breast cancer Cancer Res 65 2005 9155 9158
40. Stratton M.R., Campbell P.J., and Futreal P.A. The cancer genome Nature 458 2009 719 724
41. Forbes S.A., Tang G., and Bindal N. COSMIC (the Catalogue of Somatic Mutations in Cancer): a resource to investigate acquired mutations in human cancer Nucleic Acids Res 38 2010 D652 657
42. MacConaill L.E., Campbell C.D., and Kehoe S.M. Profiling critical cancer gene mutations in clinical tumor samples PLoS One e7887 2009 4
43. Thomas R.K., Baker A.C., and Debiasi R.M. High-throughput oncogene mutation profiling in human cancer Nat Genet 39 2007 347 351
44. Normanno N., Tejpar S., and Morgillo F. Implications for KRAS status and EGFR-targeted therapies in metastatic CRC Nat Rev Clin Oncol 6 2009 519 527
45. Chin K., DeVries S., and Fridlyand J. Genomic and transcriptional aberrations linked to breast cancer pathophysiologies Cancer Cell 10 2006 529 541
46. Hicks J., Krasnitz A., and Lakshmi B. Novel patterns of genome rearrangement and their association with survival in breast cancer Genome Res 16 2006 1465 1479
47. Turner N., Lambros M.B., and Horlings H.M. Integrative molecular profiling of triple negative breast cancers identifies amplicon drivers and potential therapeutic targets Oncogene 29 2010 2013 2023
48. Santarius T., Shipley J., and Brewer D. A census of amplified and overexpressed human cancer genes Nat Rev Cancer 10 2010 59 64
49. Natrajan R., Weigelt B., and Mackay A. An integrative genomic and transcriptomic analysis reveals molecular pathways and networks regulated by copy number aberrations in basal-like, HER2 and luminal cancers Breast Cancer Res Treat 121 2010 575 589
50. Wood L.D., Parsons D.W., and Jones S. The genomic landscapes of human breast and colorectal cancers Science 318 2007 1108 1113
51. Shah S.P., Morin R.D., and Khattra J. Mutational evolution in a lobular breast tumour profiled at single nucleotide resolution Nature 461 2009 809 813
52. Stephens P.J., McBride D.J., and Lin M.L. Complex landscapes of somatic rearrangement in human breast cancer genomes Nature 462 2009 1005 1010
53. Ding L., Ellis M.J., and Li S. Genome remodelling in a basal-like breast cancer metastasis and xenograft Nature 464 2010 999 1005
54. International network of cancer genome projects Nature 464 2010 993 998
55. Leary R.J., Kinde I., and Diehl F. Development of personalized tumor biomarkers using massively parallel sequencing Sci Transl Med 2 2010 20ra14
56. Hastings P.J., Ira G., and Lupski J.R. A microhomology-mediated break-induced replication model for the origin of human copy number variation PLoS Genet 5 2009 e1000327
57. Sarasin A., and Kauffmann A. Overexpression of DNA repair genes is associated with metastasis: a new hypothesis Mutat Res 659 2008 49 55
58. Carter S.L., Eklund A.C., and Kohane I.S. A signature of chromosomal instability inferred from gene expression profiles predicts clinical outcome in multiple human cancers Nat Genet 38 2006 1043 1048
59. Roy R., Kozlov A.G., and Lohman T.M. SSB protein diffusion on single-stranded DNA stimulates RecA filament formation Nature 461 2009 1092 1097
60. Caldecott K.W. Single-strand break repair and genetic disease Nat Rev Genet 9 2008 619 631
61. Khanna K.K., and Jackson S.P. DNA double-strand breaks: signaling, repair and the cancer connection Nat Genet 27 2001 247 254
62. Liang Y., Lin S.Y., and Brunicardi F.C. DNA damage response pathways in tumor suppression and cancer treatment World J Surg 33 2009 661 666
63. Helleday T., Lo J., and van Gent D.C. DNA double-strand break repair: from mechanistic understanding to cancer treatment DNA Repair (Amst) 6 2007 923 935
64. Richardson C., Moynahan M.E., and Jasin M. Double-strand break repair by interchromosomal recombination: suppression of chromosomal translocations Genes Dev 12 1998 3831 3842
65. Richardson C., Stark J.M., and Ommundsen M. Rad51 overexpression promotes alternative double-strand break repair pathways and genome instability Oncogene 23 2004 546 553
66. Henning W., and Sturzbecher H.W. Homologous recombination and cell cycle checkpoints: Rad51 in tumour progression and therapy resistance Toxicology 193 2003 91 109
67. Klein H.L. The consequences of Rad51 overexpression for normal and tumor cells DNA Repair (Amst) 7 2008 686 693
68. Takata M., Sasaki M.S., and Sonoda E. Homologous recombination and non-homologous end-joining pathways of DNA double-strand break repair have overlapping roles in the maintenance of chromosomal integrity in vertebrate cells EMBO J 17 1998 5497 5508
69. Rothkamm K., Kruger I., and Thompson L.H. Pathways of DNA double-strand break repair during the mammalian cell cycle Mol Cell Biol 23 2003 5706 5715
70. van Gent D.C., Hoeijmakers J.H., and Kanaar R. Chromosomal stability and the DNA double-stranded break connection Nat Rev Genet 2 2001 196 206
71. Mills K.D., Ferguson D.O., and Alt F.W. The role of DNA breaks in genomic instability and tumorigenesis Immunol Rev 194 2003 77 95
72. Elliott B., Richardson C., and Jasin M. Chromosomal translocation mechanisms at intronic alu elements in mammalian cells Mol Cell 17 2005 885 894
73. Moynahan M.E., and Jasin M. Mitotic homologous recombination maintains genomic stability and suppresses tumorigenesis Nat Rev Mol Cell Biol 11 2010 196 207
74. Weinstock D.M., Elliott B., and Jasin M. A model of oncogenic rearrangements: differences between chromosomal translocation mechanisms and simple double-strand break repair Blood 107 2006 777 780
75. Payen C., Koszul R., and Dujon B. Segmental duplications arise from Pol32-dependent repair of broken forks through two alternative replication-based mechanisms PLoS Genet 4 2008 e1000175
76. Halazonetis T.D., Gorgoulis V.G., and Bartek J. An oncogene-induced DNA damage model for cancer development Science 319 2008 1352 1355
77. Bartkova J., Horejsi Z., and Koed K. DNA damage response as a candidate anti-cancer barrier in early human tumorigenesis Nature 434 2005 864 870
78. Blow J.J., and Gillespie P.J. Replication licensing and cancer-a fatal entanglement? Nat Rev Cancer 8 2008 799 806
79. Umar A., Boland C.R., and Terdiman J.P. Revised Bethesda Guidelines for hereditary nonpolyposis colorectal cancer (Lynch syndrome) and microsatellite instability J Natl Cancer Inst 96 2004 261 268
80. Chiaravalli A.M., Furlan D., and Facco C. Immunohistochemical pattern of hMSH2/hMLH1 in familial and sporadic colorectal, gastric, endometrial and ovarian carcinomas with instability in microsatellite sequences Virchows Arch 438 2001 39 48
81. Weisenberger D.J., Siegmund K.D., and Campan M. CpG island methylator phenotype underlies sporadic microsatellite instability and is tightly associated with BRAF mutation in colorectal cancer Nat Genet 38 2006 787 793
82. Aaltonen L.A., Peltomaki P., and Leach F.S. Clues to the pathogenesis of familial colorectal cancer Science 260 1993 812 816
83. Peltomaki P. Role of DNA mismatch repair defects in the pathogenesis of human cancer J Clin Oncol 21 2003 1174 1179
84. Yee C.J., Roodi N., and Verrier C.S. Microsatellite instability and loss of heterozygosity in breast cancer Cancer Res 54 1994 1641 1644
85. Wooster R., Cleton-Jansen A.M., and Collins N. Instability of short tandem repeats (microsatellites) in human cancers Nat Genet 6 1994 152 156
86. Peltomaki P., Lothe R.A., and Aaltonen L.A. Microsatellite instability is associated with tumors that characterize the hereditary non-polyposis colorectal carcinoma syndrome Cancer Res 53 1993 5853 5855
87. Patel U., Grundfest-Broniatowski S., and Gupta M. Microsatellite instabilities at five chromosomes in primary breast tumors Oncogene 9 1994 3695 3700
88. Ellsworth R.E., Hooke J.A., and Love B. Correlation of levels and patterns of genomic instability with histological grading of invasive breast tumors Breast Cancer Res Treat 107 2008 259 265
89. Martin L., Coffey M., and Lawler M. DNA mismatch repair and the transition to hormone independence in breast and prostate cancer Cancer Lett 291 2010 142 149
90. Caldes T., Perez-Segura P., and Tosar A. Low frequency of microsatellite instability in sporadic breast cancer Int J Oncol 16 2000 1235 1242
91. Rosenberg C.L., Larson P.S., and Romo J.D. Microsatellite alterations indicating monoclonality in atypical hyperplasias associated with breast cancer Hum Pathol 28 1997 214 219
92. Siah S.P., Quinn D.M., and Bennett G.D. Microsatellite instability markers in breast cancer: a review and study showing MSI was not detected at "BAT 25" and "BAT 26" microsatellite markers in early-onset breast cancer Breast Cancer Res Treat 60 2000 135 142
93. Thomas D.C., Umar A., and Kunkel T.A. Microsatellite instability and mismatch repair defects in cancer Mutat Res 350 1996 201 205
94. Naqvi R.A., Hussain A., and Deo S.S. Hypermethylation analysis of mismatch repair genes (hmlh1 and hmsh2) in locally advanced breast cancers in Indian women Hum Pathol 39 2008 672 680
95. Muller A., Edmonston T.B., and Corao D.A. Exclusion of breast cancer as an integral tumor of hereditary nonpolyposis colorectal cancer Cancer Res 62 2002 1014 1019
96. Wong E.M., Tesoriero A.A., and Pupo G.M. Is MSH2 a breast cancer susceptibility gene? Fam Cancer 7 2008 151 155
97. de Leeuw W.J., van Puijenbroek M., and Tollenaar R.A. Correspondence re: A. Muller et al., Exclusion of breast cancer as an integral tumor of hereditary nonpolyposis colorectal cancer. Cancer Res., 62: 1014-1019, 2002 Cancer Res 63 2003 1148 1149
98. Vasen H.F., Morreau H., and Nortier J.W. Is breast cancer part of the tumor spectrum of hereditary nonpolyposis colorectal cancer? Am J Hum Genet 68 2001 1533 1535
99. Shanley S., Fung C., and Milliken J. Breast cancer immunohistochemistry can be useful in triage of some HNPCC families Fam Cancer 8 2009 251 255
100. Walsh MD, Buchanan DD, Cummings MC, et al. Lynch syndrome-associated breast cancers: clinicopathologic characteristics of a case series from the colon cancer family registry. Clin Cancer Res 16: 2214-24.
101. Wasielewski M., Riaz M., and Vermeulen J. Association of rare MSH6 variants with familial breast cancer Breast Cancer Res Treat 2009
102. Lingle W.L., Barrett S.L., and Negron V.C. Centrosome amplification drives chromosomal instability in breast tumor development Proc Natl Acad Sci U S A 99 2002 1978 1983
103. Pihan G.A., Purohit A., and Wallace J. Centrosome defects and genetic instability in malignant tumors Cancer Res 58 1998 3974 3985
104. Carroll P.E., Okuda M., and Horn H.F. Centrosome hyperamplification in human cancer: chromosome instability induced by p53 mutation and/or Mdm2 overexpression Oncogene 18 1999 1935 1944
105. Nigg E.A. Centrosome aberrations: cause or consequence of cancer progression? Nat Rev Cancer 2 2002 815 825
106. Zhou H., Kuang J., and Zhong L. Tumour amplified kinase STK15/BTAK induces centrosome amplification, aneuploidy and transformation Nat Genet 20 1998 189 193
107. Meraldi P., Honda R., and Nigg E.A. Aurora-A overexpression reveals tetraploidization as a major route to centrosome amplification in p53-/- cells EMBO J 21 2002 483 492
108. Ghadimi B.M., Sackett D.L., and Difilippantonio M.J. Centrosome amplification and instability occurs exclusively in aneuploid, but not in diploid colorectal cancer cell lines, and correlates with numerical chromosomal aberrations Genes Chromosomes Cancer 27 2000 183 190
109. Lingle W.L., and Salisbury J.L. Altered centrosome structure is associated with abnormal mitoses in human breast tumors Am J Pathol 155 1999 1941 1951
110. Persons D.L., Robinson R.A., and Hsu P.H. Chromosome-specific aneusomy in carcinoma of the breast Clin Cancer Res 2 1996 883 888
111. Pinkel D., Straume T., and Gray J.W. Cytogenetic analysis using quantitative, high-sensitivity, fluorescence hybridization Proc Natl Acad Sci U S A 83 1986 2934 2938
112. Pihan G.A., Wallace J., and Zhou Y. Centrosome abnormalities and chromosome instability occur together in pre-invasive carcinomas Cancer Res 63 2003 1398 1404
113. Lingle W.L., Lutz W.H., and Ingle J.N. Centrosome hypertrophy in human breast tumors: implications for genomic stability and cell polarity Proc Natl Acad Sci U S A 95 1998 2950 2955
114. Miyoshi Y., Iwao K., and Egawa C. Association of centrosomal kinase STK15/BTAK mRNA expression with chromosomal instability in human breast cancers Int J Cancer 92 2001 370 373
115. Palacios J., Honrado E., and Osorio A. Phenotypic characterization of BRCA1 and BRCA2 tumors based in a tissue microarray study with 37 immunohistochemical markers Breast Cancer Res Treat 90 2005 5 14
116. Lakhani S.R., Jacquemier J., and Sloane J.P. Multifactorial analysis of differences between sporadic breast cancers and cancers involving BRCA1 and BRCA2 mutations J Natl Cancer Inst 90 1998 1138 1145
117. Lakhani S.R., Reis-Filho J.S., and Fulford L. Prediction of BRCA1 status in patients with breast cancer using estrogen receptor and basal phenotype Clin Cancer Res 11 2005 5175 5180
118. Foulkes W.D., Brunet J.S., and Stefansson I.M. The prognostic implication of the basal-like (cyclin E high/p27 low/p53+/glomeruloid-microvascular- proliferation+) phenotype of BRCA1-related breast cancer Cancer Res 64 2004 830 835
119. Rakha E.A., El-Sheikh S.E., and Kandil M.A. Expression of BRCA1 protein in breast cancer and its prognostic significance Hum Pathol 39 2008 857 865
120. Beger C., Pierce L.N., and Kruger M. Identification of Id4 as a regulator of BRCA1 expression by using a ribozyme-library-based inverse genomics approach Proc Natl Acad Sci U S A 98 2001 130 135
121. Turner N.C., Reis-Filho J.S., and Russell A.M. BRCA1 dysfunction in sporadic basal-like breast cancer Oncogene 26 2007 2126 2132
122. Schmitt F.C., Soares R., and Gobbi H. Microsatellite instability in medullary breast carcinomas Int J Cancer 82 1999 644 647
123. Westenend P.J., Schutte R., and Hoogmans M.M. Breast cancer in an MSH2 gene mutation carrier Hum Pathol 36 2005 1322 1326
124. Jensen U.B., Sunde L., and Timshel S. Mismatch repair defective breast cancer in the hereditary nonpolyposis colorectal cancer syndrome Breast Cancer Res Treat 120 2010 777 782
125. Ljungman M. Targeting the DNA damage response in cancer Chem Rev 109 2009 2929 2950
126. Powell S.N., and Bindra R.S. Targeting the DNA damage response for cancer therapy DNA Repair (Amst) 8 2009 1153 1165
127. Tao Z.F., and Lin N.H. Chk1 inhibitors for novel cancer treatment Anticancer Agents Med Chem 6 2006 377 388
128. Bucher N., and Britten C.D. G2 checkpoint abrogation and checkpoint kinase-1 targeting in the treatment of cancer Br J Cancer 98 2008 523 528
129. Wang Y., Ji P., and Liu J. Centrosome-associated regulators of the G(2)/M checkpoint as targets for cancer therapy Mol Cancer 8 2009 8
130. Leahy J.J., Golding B.T., and Griffin R.J. Identification of a highly potent and selective DNA-dependent protein kinase (DNA-PK) inhibitor (NU7441) by screening of chromenone libraries Bioorg Med Chem Lett 14 2004 6083 6087
131. Griffin R.J., Fontana G., and Golding B.T. Selective benzopyranone and pyrimido[2,1-a]isoquinolin-4-one inhibitors of DNA-dependent protein kinase: synthesis, structure-activity studies, and radiosensitization of a human tumor cell line in vitro J Med Chem 48 2005 569 585
132. Hardcastle I.R., Cockcroft X., and Curtin N.J. Discovery of potent chromen-4-one inhibitors of the DNA-dependent protein kinase (DNA-PK) using a small-molecule library approach J Med Chem 48 2005 7829 7846
133. Bentle M.S., Bey E.A., and Dong Y. New tricks for old drugs: the anticarcinogenic potential of DNA repair inhibitors J Mol Histol 37 2006 203 218
134. Kelley M.R., and Fishel M.L. DNA repair proteins as molecular targets for cancer therapeutics Anticancer Agents Med Chem 8 2008 417 425
135. Lieberman H.B. DNA damage repair and response proteins as targets for cancer therapy Curr Med Chem 15 2008 360 367
136. O'Connor M.J., Martin N.M., and Smith G.C. Targeted cancer therapies based on the inhibition of DNA strand break repair Oncogene 26 2007 7816 7824
137. Hegi M.E., Sciuscio D., and Murat A. Epigenetic deregulation of DNA repair and its potential for therapy Clin Cancer Res 15 2009 5026 5031
138. Rottenberg S., Jaspers J.E., and Kersbergen A. 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 105 2008 17079 17084
139. Farmer H., McCabe N., and Lord C.J. Targeting the DNA repair defect in BRCA mutant cells as a therapeutic strategy Nature 434 2005 917 921
140. Bryant H.E., Schultz N., and Thomas H.D. Specific killing of BRCA2-deficient tumours with inhibitors of poly(ADP-ribose) polymerase Nature 434 2005 913 917
141. Ashworth A. 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 2008 3785 3790
142. Martin S.A., McCabe N., and Mullarkey M. DNA polymerases as potential therapeutic targets for cancers deficient in the DNA mismatch repair proteins MSH2 or MLH1 Cancer Cell 17 2010 235 248
143. Haber J.E. DNA recombination: the replication connection Trends Biochem Sci 24 1999 271 275
144. Lomonosov M., Anand S., and Sangrithi M. Stabilization of stalled DNA replication forks by the BRCA2 breast cancer susceptibility protein Genes Dev 17 2003 3017 3022
145. Vaziri H., West M.D., and Allsopp R.C. ATM-dependent telomere loss in aging human diploid fibroblasts and DNA damage lead to the post-translational activation of p53 protein involving poly(ADP-ribose) polymerase EMBO J 16 1997 6018 6033
146. Hay T., Jenkins H., and Sansom O.J. Efficient deletion of normal Brca2-deficient intestinal epithelium by poly(ADP-ribose) polymerase inhibition models potential prophylactic therapy Cancer Res 65 2005 10145 10148
147. Loh V.M. Jr., Cockcroft X.L., and Dillon K.J. Phthalazinones. Part 1: the design and synthesis of a novel series of potent inhibitors of poly (ADP-ribose)polymerase Bioorg Med Chem Lett 15 2005 2235 2238
148. Edwards S.L., Brough R., and Lord C.J. Resistance to therapy caused by intragenic deletion in BRCA2 Nature 451 2008 1111 1115
149. Waddell N., Arnold J., and Cocciardi S. Subtypes of familial breast tumours revealed by expression and copy number profiling Breast Cancer Res Treat 2009 [Epub ahead of print]
150. Martin R.W., Orelli B.J., and Yamazoe M. RAD51 up-regulation bypasses BRCA1 function and is a common feature of BRCA1-deficient breast tumors Cancer Res 67 2007 9658 9665
151. Bouwman P., Aly A., and Escandell J.M. 53BP1 loss rescues BRCA1 deficiency and is associated with triple-negative and BRCA-mutated breast cancers Nat Struct Mol Biol 17 2010 688 695
152. Bunting S.F., Callen E., and Wong N. 53BP1 inhibits homologous recombination in Brca1-deficient cells by blocking resection of DNA breaks Cell 141 2010 243 254
153. Boulton S.J. DNA repair: Decision at the break point Nature 465 2010 301 302
154. Kass E.M., Moynahan M.E., and Jasin M. Loss of 53BP1 is a gain for BRCA1 mutant cells Cancer Cell 17 2010 423 425
155. Goldsmith K.C., Liu X., and Dam V. BH3 peptidomimetics potently activate apoptosis and demonstrate single agent efficacy in neuroblastoma Oncogene 25 2006 4525 4533
156. Kolluri S.K., Zhu X., and Zhou X. A short Nur77-derived peptide converts Bcl-2 from a protector to a killer Cancer Cell 14 2008 285 298
157. Carey L.A., Dees E.C., and Sawyer L. The triple negative paradox: primary tumor chemosensitivity of breast cancer subtypes Clin Cancer Res 13 2007 2329 2334
158. Goldstein L.J., O'Neill A., and Sparano J.A. Concurrent doxorubicin plus docetaxel is not more effective than concurrent doxorubicin plus cyclophosphamide in operable breast cancer with 0 to 3 positive axillary nodes: North American Breast Cancer Intergroup Trial E 2197. J Clin Oncol 26 2008 4092 4099
159. Keam B., Im S.A., and Kim H.J. Prognostic impact of clinicopathologic parameters in stage II/III breast cancer treated with neoadjuvant docetaxel and doxorubicin chemotherapy: paradoxical features of the triple negative breast cancer BMC Cancer 7 2007 203
160. Tercero J.A., and Diffley J.F. Regulation of DNA replication fork progression through damaged DNA by the Mec1/Rad53 checkpoint Nature 412 2001 553 557
161. Howlett N.G., Taniguchi T., and Olson S. Biallelic inactivation of BRCA2 in Fanconi anemia Science 297 2002 606 609
162. Kraakman-van der Zwet M., Overkamp W.J., and van Lange R.E. Brca2 (XRCC11) deficiency results in radioresistant DNA synthesis and a higher frequency of spontaneous deletions Mol Cell Biol 22 2002 669 679
163. Bartz S.R., Zhang Z., and Burchard J. Small interfering RNA screens reveal enhanced cisplatin cytotoxicity in tumor cells having both BRCA network and TP53 disruptions Mol Cell Biol 26 2006 9377 9386
164. Jaspers J.E., Rottenberg S., and Jonkers J. Therapeutic options for triple-negative breast cancers with defective homologous recombination Biochim Biophys Acta 1796 2009 266 280
165. O'Shaughnessy J., Osborne C., and Pippen J. Efficacy of BSI-201, a poly (ADP-ribose) polymerase-1 (PARP1) inhibitor, in combination with gemcitabine/carboplatin (G/C) in patients with metastatic triple-negative breast cancer (TNBC): results of a randomized phase II trial J Clin Oncol (Meeting Abstracts) 27 2009 3
166. Ford D., Easton D.F., and Stratton M. Genetic heterogeneity and penetrance analysis of the BRCA1 and BRCA2 genes in breast cancer families. The Breast Cancer Linkage Consortium Am J Hum Genet 62 1998 676 689
167. Antoniou A., Pharoah P.D., and Narod S. 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 2003 1117 1130
168. Mavaddat N., Rebbeck T.R., and Lakhani S.R. Incorporating tumour pathology information into breast cancer risk prediction algorithms Breast Cancer Res 12 2010 R28
169. Chenevix-Trench G., Healey S., and Lakhani S. Genetic and histopathologic evaluation of BRCA1 and BRCA2 DNA sequence variants of unknown clinical significance Cancer Res 66 2006 2019 2027
170. Tommasi S., Pilato B., and Pinto R. Molecular and in silico analysis of BRCA1 and BRCA2 variants Mutat Res 644 2008 64 70
171. Spearman A.D., Sweet K., and Zhou X.P. Clinically applicable models to characterize BRCA1 and BRCA2 variants of uncertain significance J Clin Oncol 26 2008 5393 5400
172. Wacholder S., Hartge P., and Prentice R. Performance of common genetic variants in breast-cancer risk models N Engl J Med 362 2010 986 993