Targeted Therapies for Triple-Negative Breast Cancer: Combating a Stubborn Disease

Trends in Pharmacological Sciences

Volumn 36, Issue 12, 2015, Pages 822-846

  Kalimutho, Murugan ^a   Parsons, Kate ^a,b   Mittal, Deepak ^a   López, J Alejandro ^a,b   Srihari, Sriganesh ^c   Khanna, Kum Kum ^a,b  

^a QIMR BERGHOFER MEDICAL RESEARCH INSTITUTE   (Australia)

^b GRIFFITH UNIVERSITY   (Australia)

^c UNIVERSITY OF QUEENSLAND   (Australia)

Author keywords

[No Author keywords available]

Indexed keywords

5' NUCLEOTIDASE; ANTHRACYCLINE; BENDAMUSTINE; CAPECITABINE; CARBOPLATIN; CHECKPOINT KINASE 1; CHECKPOINT KINASE 2; CISPLATIN; CYCLIN DEPENDENT KINASE; DOCETAXEL; DOXORUBICIN; ERIBULIN; ERLOTINIB; EVEROLIMUS; GEMCITABINE; INIPARIB; METFORMIN; NIMOTUZUMAB; OLAPARIB; PACLITAXEL; PANITUMUMAB; PLATINUM DERIVATIVE; PROTEIN PD L1; SUNITINIB; TAXANE DERIVATIVE; TRAMETINIB; TUMOR PROTEIN; UNCLASSIFIED DRUG; UNINDEXED DRUG; UPROSERTIB; VELIPARIB;

APOPTOSIS; CANCER COMBINATION CHEMOTHERAPY; CANCER IMMUNOTHERAPY; CANCER PROGNOSIS; CANCER RESISTANCE; CELL CYCLE REGULATION; DNA DAMAGE; DRUG EFFICACY; ENZYME INHIBITION; GENE EXPRESSION; HUMAN; IMMUNE RESPONSE; IMMUNOMODULATION; LYMPHOCYTIC INFILTRATION; MOLECULAR MODEL; MOLECULARLY TARGETED THERAPY; NONHUMAN; PRIORITY JOURNAL; PROTEIN EXPRESSION; REVIEW; TRIPLE NEGATIVE BREAST CANCER; TUMOR ASSOCIATED LEUKOCYTE; ANIMAL; FEMALE; GENETICS; PATHOLOGY; TRIPLE NEGATIVE BREAST NEOPLASMS;

ANIMALS; FEMALE; HUMANS; MOLECULAR TARGETED THERAPY; TRIPLE NEGATIVE BREAST NEOPLASMS;

EID: 84942629362     PISSN: 01656147     EISSN: 18733735     Source Type: Journal    
DOI: 10.1016/j.tips.2015.08.009     Document Type: Review

References (249)

1. B.W. Stewart, and et al. World Cancer Report 2014 2014 International Agency for Research on Cancer
2. A. Jemal, and et al. Global cancer statistics CA Cancer J. Clin. 61 2011 69 90
3. C.M. Perou, and et al. Molecular portraits of human breast tumours Nature 406 2000 747 752
4. T. Sorlie, and et al. Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications Proc. Natl. Acad. Sci. U.S.A. 98 2001 10869 10874
5. T. Sorlie, and et al. Repeated observation of breast tumor subtypes in independent gene expression data sets Proc. Natl. Acad. Sci, U.S.A. 100 2003 8418 8423
6. C. Fan, and et al. Concordance among gene-expression-based predictors for breast cancer N. Engl. J. Med. 355 2006 560 569
7. S. Paik, and et al. A multigene assay to predict recurrence of tamoxifen-treated, node-negative breast cancer N. Engl. J. Med. 351 2004 2817 2826
8. M. Dowsett, and et al. Prediction of risk of distant recurrence using the 21-gene recurrence score in node-negative and node-positive postmenopausal patients with breast cancer treated with anastrozole or tamoxifen: a TransATAC study J. Clin. Oncol. 28 2010 1829 1834
9. O. Metzger-Filho, and et al. Patterns of recurrence and outcome according to breast cancer subtypes in lymph node-negative disease: results from international breast cancer study group trials VIII and IX J. Clin. Oncol. 31 2013 3083 3090
10. N.D. Arvold, and et al. Age, breast cancer subtype approximation, and local recurrence after breast-conserving therapy J. Clin. Oncol. 29 2011 3885 3891
11. R. Haque, and et al. Impact of breast cancer subtypes and treatment on survival: an analysis spanning two decades Cancer Epidemiol. Biomarkers Prev. 21 2012 1848 1855
12. P. Eroles, and et al. Molecular biology in breast cancer: intrinsic subtypes and signaling pathways Cancer Treat. Rev. 38 2012 698 707
13. G. Cancello, and et al. Progesterone receptor loss identifies luminal B breast cancer subgroups at higher risk of relapse Ann. Oncol. 24 2013 661 668
14. F. Ades, and et al. Luminal B breast cancer: molecular characterization, clinical management, and future perspectives J. Clin. Oncol. 32 2014 2794 2803
15. S.J. Schnitt Classification and prognosis of invasive breast cancer: from morphology to molecular taxonomy Mod. Pathol. 23 Suppl. 2 2010 S60 S64
16. J.S. Ross, and et al. The HER-2 receptor and breast cancer: ten years of targeted anti-HER-2 therapy and personalized medicine Oncologist 14 2009 320 368
17. E.A. Rakha, and et al. Are triple-negative tumours and basal-like breast cancer synonymous? Breast Cancer Res. 9 2007 404
18. E. Rakha, and et al. Are triple-negative and basal-like breast cancer synonymous? Clin. Cancer Res. 14 2008 618
19. H. Masuda, and et al. Differential response to neoadjuvant chemotherapy among 7 triple-negative breast cancer molecular subtypes Clin. Cancer Res. 19 2013 5533 5540
20. B.D. Lehmann, and et al. Identification of human triple-negative breast cancer subtypes and preclinical models for selection of targeted therapies J. Clin. Invest. 121 2011 2750 2767
21. M.C. Cheang, and et al. Basal-like breast cancer defined by five biomarkers has superior prognostic value than triple-negative phenotype Clin. Cancer Res. 14 2008 1368 1376
22. L.A. Carey, and et al. The triple negative paradox: primary tumor chemosensitivity of breast cancer subtypes Clin. Cancer Res. 13 2007 2329 2334
23. C. Liedtke, and et al. Response to neoadjuvant therapy and long-term survival in patients with triple-negative breast cancer J. Clin. Oncol. 26 2008 1275 1281
24. J.M. Balko, and et al. Molecular profiling of the residual disease of triple-negative breast cancers after neoadjuvant chemotherapy identifies actionable therapeutic targets Cancer Discov. 4 2014 232 245
25. H. Masuda, and et al. Predictive factors for the effectiveness of neoadjuvant chemotherapy and prognosis in triple-negative breast cancer patients Cancer Chemother. Pharmacol. 67 2011 911 917
26. F. Podo, and et al. Triple-negative breast cancer: present challenges and new perspectives Mol. Oncol. 4 2010 209 229
27. L. Carey, and et al. Triple-negative breast cancer: disease entity or title of convenience? Nat. Rev. Clin. Oncol. 7 2010 683 692
28. W.D. Foulkes, and et al. Triple-negative breast cancer N. Engl. J. Med. 363 2010 1938 1948
29. L.G. Fulford, and et al. Basal-like grade III invasive ductal carcinoma of the breast: patterns of metastasis and long-term survival Breast Cancer Res. 9 2007 R4
30. R. Dent, and et al. Pattern of metastatic spread in triple-negative breast cancer Breast Cancer Res. Treat. 115 2009 423 428
31. W.D. Foulkes, and et al. Tumor size is an unreliable predictor of prognosis in basal-like breast cancers and does not correlate closely with lymph node status Breast Cancer Res. Treat. 117 2009 199 204
32. S.J. Crabb, and et al. Basal breast cancer molecular subtype predicts for lower incidence of axillary lymph node metastases in primary breast cancer Clin. Breast Cancer 8 2008 249 256
33. W.D. Foulkes, and et al. Disruption of the expected positive correlation between breast tumor size and lymph node status in BRCA1-related breast carcinoma Cancer 98 2003 1569 1577
34. F.M. Blows, and et al. Subtyping of breast cancer by immunohistochemistry to investigate a relationship between subtype and short and long term survival: a collaborative analysis of data for 10,159 cases from 12 studies PLoS Med. 7 2010 e1000279
35. M.L. Gatza, and et al. A pathway-based classification of human breast cancer Proc. Natl. Acad. Sci. U.S.A. 107 2010 6994 6999
36. C. Curtis, and et al. The genomic and transcriptomic architecture of 2,000 breast tumours reveals novel subgroups Nature 486 2012 346 352
37. H.R. Ali, and et al. Genome-driven integrated classification of breast cancer validated in over 7,500 samples Genome Biol. 15 2014 431
38. A.A. Margolin, and et al. Systematic analysis of challenge-driven improvements in molecular prognostic models for breast cancer Sci Transl. Med. 5 2013 181re181
39. W.Y. Cheng, and et al. Development of a prognostic model for breast cancer survival in an open challenge environment Sci. Transl. Med. 5 2013 181ra150
40. The Cancer Genome Atlas Network Comprehensive molecular portraits of human breast tumours Nature 490 2012 61 70
41. S.P. Shah, and et al. The clonal and mutational evolution spectrum of primary triple-negative breast cancers Nature 486 2012 395 399
42. M.D. Burstein, and et al. Comprehensive genomic analysis identifies novel subtypes and targets of triple-negative breast cancer Clin. Cancer Res. 21 2015 1688 1698
43. H. Xu, and et al. The omics of triple-negative breast cancers Clin. Chem. 60 2014 122 133
44. F. Petrelli, and et al. The value of platinum agents as neoadjuvant chemotherapy in triple-negative breast cancers: a systematic review and meta-analysis Breast Cancer Res. Treat. 144 2014 223 232
45. B. Kreike, and et al. Gene expression profiling and histopathological characterization of triple-negative/basal-like breast carcinomas Breast Cancer Res. 9 2007 R65
46. S. Badve, and et al. Basal-like and triple-negative breast cancers: a critical review with an emphasis on the implications for pathologists and oncologists Mod. Pathol. 24 2011 157 167
47. C.K. Ng, and et al. Breast cancer genomics from microarrays to massively parallel sequencing: paradigms and new insights J. Natl. Cancer Inst. 2015 10.1093/jnci/djv015 Published online February 23, 2015
48. B. Jovanovic, and et al. Transforming growth factor beta receptor type III is a tumor promoter in mesenchymal-stem like triple negative breast cancer Breast Cancer Res. 16 2014 R69
49. B.D. Lehmann, and et al. PIK3CA mutations in androgen receptor-positive triple negative breast cancer confer sensitivity to the combination of PI3K and androgen receptor inhibitors Breast Cancer Res. 16 2014 406
50. V.G. Abramson, and et al. Subtyping of triple-negative breast cancer: implications for therapy Cancer 121 2015 8 16
51. I.A. Mayer Subtyping of triple-negative breast cancer Clin. Adv. Hematol. Oncol. 11 2013 731 732
52. E.H. Lips, and et al. Triple-negative breast cancer: BRCAness and concordance of clinical features with BRCA1-mutation carriers Br. J. Cancer 108 2013 2172 2177
53. M.W. Seong, and et al. A multi-institutional study on the association between BRCA1/BRCA2 mutational status and triple-negative breast cancer in familial breast cancer patients Breast Cancer Res. Treat. 146 2014 63 69
54. F.J. Couch, and 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. 33 2015 304 311
55. M.W. Audeh Novel treatment strategies in triple-negative breast cancer: specific role of poly(adenosine diphosphate-ribose) polymerase inhibition Pharmgenomics Pers. Med. 7 2014 307 316
56. C.K. Anders, and et al. Poly(ADP-Ribose) polymerase inhibition: 'targeted' therapy for triple-negative breast cancer Clin. Cancer Res. 16 2010 4702 4710
57. H. Farmer, and et al. Targeting the DNA repair defect in BRCA mutant cells as a therapeutic strategy Nature 434 2005 917 921
58. H.E. Bryant, and et al. Specific killing of BRCA2-deficient tumours with inhibitors of poly(ADP-ribose) polymerase Nature 434 2005 913 917
59. N.J. Birkbak, and et al. Telomeric allelic imbalance indicates defective DNA repair and sensitivity to DNA-damaging agents Cancer Discov. 2 2012 366 375
60. K.A. Naipal, and et al. Functional ex vivo assay to select homologous recombination-deficient breast tumors for PARP inhibitor treatment Clin. Cancer Res. 20 2014 4816 4826
61. J.A. Watkins, and et al. Genomic scars as biomarkers of homologous recombination deficiency and drug response in breast and ovarian cancers Breast Cancer Res. 16 2014 211
62. G. Peng, and et al. Genome-wide transcriptome profiling of homologous recombination DNA repair Nat. Commun. 5 2014 3361
63. C. To, and 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.) 7 2014 698 707
64. Y. Shi, and et al. PARP inhibitor reduces proliferation and increases apoptosis in breast cancer cells Chin. J. Cancer Res. 26 2014 142 147
65. J. O'Shaughnessy, and et al. Iniparib plus chemotherapy in metastatic triple-negative breast cancer N. Engl. J. Med. 364 2011 205 214
66. J. O'Shaughnessy, and 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. 32 2014 3840 3847
67. X. Liu, and et al. Iniparib nonselectively modifies cysteine-containing proteins in tumor cells and is not a bona fide PARP inhibitor Clin. Cancer Res. 18 2012 510 523
68. A. Tutt, and 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 376 2010 235 244
69. R.A. Dent, and 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. 15 2013 R88
70. K.A. Gelmon, and 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. 12 2011 852 861
71. C. Speers, and et al. Identification of novel kinase targets for the treatment of estrogen receptor-negative breast cancer Clin. Cancer Res. 15 2009 6327 6340
72. Z.C. Hartman, and et al. Growth of triple-negative breast cancer cells relies upon coordinate autocrine expression of the proinflammatory cytokines IL-6 and IL-8 Cancer Res. 73 2013 3470 3480
73. N. Dey, and et al. Differential activation of Wnt-beta-catenin pathway in triple negative breast cancer increases MMP7 in a PTEN dependent manner PLoS ONE 8 2013 e77425
74. N. Dey, and et al. Wnt signaling in triple negative breast cancer is associated with metastasis BMC Cancer 13 2013 537
75. B. Bilir, and et al. Wnt signaling blockage inhibits cell proliferation and migration, and induces apoptosis in triple-negative breast cancer cells J. Transl. Med. 11 2013 280
76. T.D. King, and et al. The Wnt/beta-catenin signaling pathway: a potential therapeutic target in the treatment of triple negative breast cancer J. Cell. Biochem. 113 2012 13 18
77. F. Al-Ejeh, and et al. Meta-analysis of the global gene expression profile of triple-negative breast cancer identifies genes for the prognostication and treatment of aggressive breast cancer Oncogenesis 3 2014 e100
78. Y.H. Hsu, and et al. Definition of PKC-alpha, CDK6, and MET as therapeutic targets in triple-negative breast cancer Cancer Res. 74 2014 4822 4835
79. T.S. Gujral, and et al. Profiling phospho-signaling networks in breast cancer using reverse-phase protein arrays Oncogene 32 2013 3470 3476
80. J. Sonntag, and et al. Subtyping of breast cancer using reverse phase protein arrays Expert Rev. Proteomics 11 2014 757 770
81. D. Kamel, and et al. Proteomic classification of breast cancer Curr. Drug Targets 13 2012 1495 1509
82. A.M. Gonzalez-Angulo, and et al. Functional proteomics can define prognosis and predict pathologic complete response in patients with breast cancer Clin. Proteomics 8 2011 11
83. R.T. Lawrence, and et al. The proteomic landscape of triple-negative breast cancer Cell Rep. 11 2015 630 644
84. F. Hochgrafe, and et al. Tyrosine phosphorylation profiling reveals the signaling network characteristics of Basal breast cancer cells Cancer Res. 70 2010 9391 9401
85. H.U. Osmanbeyoglu, and et al. Linking signaling pathways to transcriptional programs in breast cancer Genome Res. 24 2014 1869 1880
86. T. Cabezon, and et al. Proteomic profiling of triple-negative breast carcinomas in combination with a three-tier orthogonal technology approach identifies Mage-A4 as potential therapeutic target in estrogen receptor negative breast cancer Mol. Cell. Proteomics 12 2013 381 394
87. F. Al-Ejeh, and et al. Kinome profiling reveals breast cancer heterogeneity and identifies targeted therapeutic opportunities for triple negative breast cancer Oncotarget 5 2014 3145 3158
88. J. Zhang, and S.N. Hochwald Targeting receptor tyrosine kinases in solid tumors Surg. Oncol. Clin. N. Am. 22 2013 685 703
89. A. Gschwind, and et al. The discovery of receptor tyrosine kinases: targets for cancer therapy Nat. Rev. Cancer 4 2004 361 370
90. H. Song, and et al. Targeting aberrant DNA double-strand break repair in triple-negative breast cancer with alpha-particle emitter radiolabeled anti-EGFR antibody Mol. Cancer Ther. 12 2013 2043 2054
91. Y.L. Yu, and et al. Targeting the EGFR/PCNA signaling suppresses tumor growth of triple-negative breast cancer cells with cell-penetrating PCNA peptides PLoS ONE 8 2013 e61362
92. N.T. Ueno, and D. Zhang Targeting EGFR in triple negative breast cancer J. Cancer 2 2011 324 328
93. F. Al-Ejeh, and et al. Treatment of triple-negative breast cancer using anti-EGFR-directed radioimmunotherapy combined with radiosensitizing chemotherapy and PARP inhibitor J. Nucl. Med. 54 2013 913 921
94. B. Corkery, and et al. Epidermal growth factor receptor as a potential therapeutic target in triple-negative breast cancer Ann. Oncol. 20 2009 862 867
95. R. Sharpe, and et al. FGFR signaling promotes the growth of triple-negative and basal-like breast cancer cell lines both in vitro and in vivo Clin. Cancer Res. 17 2011 5275 5286
96. N. Turner, and et al. Integrative molecular profiling of triple negative breast cancers identifies amplicon drivers and potential therapeutic targets Oncogene 29 2010 2013 2023
97. N.E. Bhola, and et al. TGF-beta inhibition enhances chemotherapy action against triple-negative breast cancer J. Clin. Invest. 123 2013 1348 1358
98. M. Jechlinger, and et al. Autocrine PDGFR signaling promotes mammary cancer metastasis J. Clin. Invest. 116 2006 1561 1570
99. Y. Zhu, and et al. C-kit and PDGFRA gene mutations in triple negative breast cancer Int. J. Clin. Exp. Pathol. 7 2014 4280 4285
100. I. Carvalho, and et al. Overexpression of platelet-derived growth factor receptor alpha in breast cancer is associated with tumour progression Breast Cancer Res. 7 2005 R788 R795
101. S. Greenberg, and H.S. Rugo Triple-negative breast cancer: role of antiangiogenic agents Cancer J. 16 2010 33 38
102. S.F. Dent The role of VEGF in triple-negative breast cancer: where do we go from here? Ann. Oncol. 20 2009 1615 1617
103. A.S. Meyer, and et al. The receptor AXL diversifies EGFR signaling and limits the response to EGFR-targeted inhibitors in triple-negative breast cancer cells Sci. Signal. 6 2013 ra66
104. J. Sohn, and et al. cMET activation and EGFR-directed therapy resistance in triple-negative breast cancer J. Cancer 5 2014 745 753
105. P.B. Gaule, and et al. cMET in triple-negative breast cancer: is it a therapeutic target for this subset of breast cancer patients? Expert Opin. Ther. Targets 18 2014 999 1009
106. B.C. Litzenburger, and et al. High IGF-IR activity in triple-negative breast cancer cell lines and tumorgrafts correlates with sensitivity to anti-IGF-IR therapy Clin. Cancer Res. 17 2011 2314 2327
107. D. Tryfonopoulos, and et al. Src: a potential target for the treatment of triple-negative breast cancer Ann. Oncol. 22 2011 2234 2240
108. J. Schlessinger Receptor tyrosine kinases: legacy of the first two decades Cold Spring Harb. Perspect. Biol. 6 2014 a008912
109. P. Krejci, and et al. Receptor tyrosine kinases activate canonical WNT/beta-catenin signaling via MAP kinase/LRP6 pathway and direct beta-catenin phosphorylation PLoS ONE 7 2012 e35826
110. S. Banerji, and et al. Sequence analysis of mutations and translocations across breast cancer subtypes Nature 486 2012 405 409
111. P.J. Stephens, and et al. The landscape of cancer genes and mutational processes in breast cancer Nature 486 2012 400 404
112. D.N. Amin, and et al. Resiliency and vulnerability in the HER2-HER3 tumorigenic driver Sci. Transl. Med. 2 2010 16ra17
113. N.V. Sergina, and et al. Escape from HER-family tyrosine kinase inhibitor therapy by the kinase-inactive HER3 Nature 445 2007 437 441
114. L.A. Carey, and et al. TBCRC 001: randomized phase II study of cetuximab in combination with carboplatin in stage IV triple-negative breast cancer J. Clin. Oncol. 30 2012 2615 2623
115. J. Baselga, and et al. Randomized phase II study of the anti-epidermal growth factor receptor monoclonal antibody cetuximab with cisplatin versus cisplatin alone in patients with metastatic triple-negative breast cancer J. Clin. Oncol. 31 2013 2586 2592
116. K. Imai, and A. Takaoka Comparing antibody and small-molecule therapies for cancer Nat. Rev. Cancer 6 2006 714 727
117. P. Matar, and et al. Combined epidermal growth factor receptor targeting with the tyrosine kinase inhibitor gefitinib (ZD1839) and the monoclonal antibody cetuximab (IMC-C225): superiority over single-agent receptor targeting Clin. Cancer Res. 10 2004 6487 6501
118. M.D. Coltrera, and et al. Expression of platelet-derived growth factor B-chain and the platelet-derived growth factor receptor beta subunit in human breast tissue and breast carcinoma Cancer Res. 55 1995 2703 2708
119. M.T. Weigel, and et al. In vitro effects of imatinib mesylate on radiosensitivity and chemosensitivity of breast cancer cells BMC Cancer 10 2010 412
120. B.K. Linderholm, and et al. Significantly higher levels of vascular endothelial growth factor (VEGF) and shorter survival times for patients with primary operable triple-negative breast cancer Ann. Oncol. 20 2009 1639 1646
121. W.L. Tam, and R.A. Weinberg The epigenetics of epithelial-mesenchymal plasticity in cancer Nat. Med. 19 2013 1438 1449
122. W.L. Tam, and et al. Protein kinase C alpha is a central signaling node and therapeutic target for breast cancer stem cells Cancer Cell 24 2013 347 364
123. B.D. Smith Imatinib for chronic myeloid leukemia: the impact of its effectiveness and long-term side effects J. Natl. Cancer Inst. 103 2011 527 529
124. E. Chinchar, and et al. Sunitinib significantly suppresses the proliferation, migration, apoptosis resistance, tumor angiogenesis and growth of triple-negative breast cancers but increases breast cancer stem cells Vasc. Cell 6 2014 12
125. B.S. Yadav, and et al. Systemic treatment strategies for triple-negative breast cancer World J. Clin. Oncol. 5 2014 125 133
126. I. Kumler, and et al. A systematic review of bevacizumab efficacy in breast cancer Cancer Treat. Rev. 40 2014 960 973
127. W.M. Sikov, and 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. 33 2015 13 21
128. P.J. Roberts, and C.J. Der Targeting the Raf-MEK-ERK mitogen-activated protein kinase cascade for the treatment of cancer Oncogene 26 2007 3291 3310
129. A.S. Dhillon, and et al. MAP kinase signalling pathways in cancer Oncogene 26 2007 3279 3290
130. J.M. Giltnane, and J.M. Balko Rationale for targeting the Ras/MAPK pathway in triple-negative breast cancer Discov. Med. 17 2014 275 283
131. J.S. Duncan, and et al. Dynamic reprogramming of the kinome in response to targeted MEK inhibition in triple-negative breast cancer Cell 149 2012 307 321
132. K.P. Hoeflich, and et al. In vivo antitumor activity of MEK and phosphatidylinositol 3-kinase inhibitors in basal-like breast cancer models Clin. Cancer Res. 15 2009 4649 4664
133. O.K. Mirzoeva, and et al. Basal subtype and MAPK/ERK kinase (MEK)-phosphoinositide 3-kinase feedback signaling determine susceptibility of breast cancer cells to MEK inhibition Cancer Res. 69 2009 565 572
134. E. Cerami, and et al. The cBio cancer genomics portal: an open platform for exploring multidimensional cancer genomics data Cancer Discov. 2 2012 401 404
135. T.J. Grob, and et al. Rare oncogenic mutations of predictive markers for targeted therapy in triple-negative breast cancer Breast Cancer Res. Treat. 134 2012 561 567
136. A. Sanchez-Munoz, and et al. Lack of evidence for KRAS oncogenic mutations in triple-negative breast cancer BMC Cancer 10 2010 136
137. E. Tilch, and et al. Mutations in EGFR, BRAF and RAS are rare in triple-negative and basal-like breast cancers from Caucasian women Breast Cancer Res. Treat. 143 2014 385 392
138. D.W. Craig, and et al. Genome and transcriptome sequencing in prospective metastatic triple-negative breast cancer uncovers therapeutic vulnerabilities Mol. Cancer Ther. 12 2013 104 116
139. M.D. Wallace, and et al. Comparative oncogenomics implicates the neurofibromin 1 gene (NF1) as a breast cancer driver Genetics 192 2012 385 396
140. J.M. Balko, and et al. Profiling of residual breast cancers after neoadjuvant chemotherapy identifies DUSP4 deficiency as a mechanism of drug resistance Nat. Med. 18 2012 1052 1059
141. C. Bartholomeusz, and et al. High ERK protein expression levels correlate with shorter survival in triple-negative breast cancer patients Oncologist 17 2012 766 774
142. C. Robert, and et al. Selumetinib plus dacarbazine versus placebo plus dacarbazine as first-line treatment for BRAF-mutant metastatic melanoma: a phase 2 double-blind randomised study Lancet Oncol. 14 2013 733 740
143. P.A. Ascierto, and et al. MEK162 for patients with advanced melanoma harbouring NRAS or Val600 BRAF mutations: a non-randomised, open-label phase 2 study Lancet Oncol. 14 2013 249 256
144. J. Farley, and et al. Selumetinib in women with recurrent low-grade serous carcinoma of the ovary or peritoneum: an open-label, single-arm, phase 2 study Lancet Oncol. 14 2013 134 140
145. J.M. Kirkwood, and et al. Phase II, open-label, randomized trial of the MEK1/2 inhibitor selumetinib as monotherapy versus temozolomide in patients with advanced melanoma Clin. Cancer Res. 18 2012 555 567
146. E. Aksamitiene, and et al. Cross-talk between mitogenic Ras/MAPK and survival PI3K/Akt pathways: a fine balance Biochem. Soc. Trans. 40 2012 139 146
147. D.A. Fruman, and C. Rommel PI3K and cancer: lessons, challenges and opportunities Nat. Rev. Drug Discov. 13 2014 140 156
148. C.G. Fedele, and et al. Inositol polyphosphate 4-phosphatase II regulates PI3K/Akt signaling and is lost in human basal-like breast cancers Proc. Natl. Acad. Sci. U.S.A. 107 2010 22231 22236
149. C. Gewinner, and et al. Evidence that inositol polyphosphate 4-phosphatase type II is a tumor suppressor that inhibits PI3K signaling Cancer Cell 16 2009 115 125
150. V. Gordon, and S. Banerji Molecular pathways: PI3K pathway targets in triple-negative breast cancers Clin. Cancer Res. 19 2013 3738 3744
151. M. Yunokawa, and et al. Efficacy of everolimus, a novel mTOR inhibitor, against basal-like triple-negative breast cancer cells Cancer Sci. 103 2012 1665 1671
152. Y.R. Chin, and et al. Targeting Akt3 signaling in triple-negative breast cancer Cancer Res. 74 2014 964 973
153. J.C. Montero, and et al. Active kinase profiling, genetic and pharmacological data define mTOR as an important common target in triple-negative breast cancer Oncogene 33 2014 148 156
154. P. Ganesan, and et al. Triple-negative breast cancer patients treated at MD Anderson Cancer Center in phase I trials: improved outcomes with combination chemotherapy and targeted agents Mol. Cancer Ther. 13 2014 3175 3184
155. Y.H. Ibrahim, and et al. PI3K inhibition impairs BRCA1/2 expression and sensitizes BRCA-proficient triple-negative breast cancer to PARP inhibition Cancer Discov. 2 2012 1036 1047
156. A. Juvekar, and et al. Combining a PI3K inhibitor with a PARP inhibitor provides an effective therapy for BRCA1-related breast cancer Cancer Discov. 2 2012 1048 1063
157. A.M. Mendes-Pereira, and et al. Synthetic lethal targeting of PTEN mutant cells with PARP inhibitors EMBO Mol. Med. 1 2009 315 322
158. P.A. Furth STAT signaling in different breast cancer sub-types Mol. Cell. Endocrinol. 382 2014 612 615
159. A. Britschgi, and et al. JAK2/STAT5 inhibition circumvents resistance to PI3K/mTOR blockade: a rationale for cotargeting these pathways in metastatic breast cancer Cancer Cell 22 2012 796 811
160. - stem cell-like breast cancer cells in human tumors J. Clin. Invest. 121 2011 2723 2735
161. W. Wei, and et al. STAT3 signaling is activated preferentially in tumor-initiating cells in claudin-low models of human breast cancer Stem Cells 32 2014 2571 2582
162. B.J. Shields, and et al. TCPTP regulates SFK and STAT3 signaling and is lost in triple-negative breast cancers Mol. Cell. Biol. 33 2013 557 570
163. P. Dent, and et al. CHK1 inhibitors in combination chemotherapy: thinking beyond the cell cycle Mol. Interv. 11 2011 133 140
164. I. Takahashi, and et al. UCN-01, a selective inhibitor of protein kinase C from Streptomyces J. Antibiot. 40 1987 1782 1784
165. R.T. Bunch, and A. Eastman Enhancement of cisplatin-induced cytotoxicity by 7-hydroxystaurosporine (UCN-01), a new G2-checkpoint inhibitor Clin. Cancer Res. 2 1996 791 797
166. E.C. Dees, and et al. A phase I and pharmacokinetic study of short infusions of UCN-01 in patients with refractory solid tumors Clin. Cancer Res. 11 2005 664 671
167. M. Castedo, and et al. The cell cycle checkpoint kinase Chk2 is a negative regulator of mitotic catastrophe Oncogene 23 2004 4353 4361
168. C.X. Ma, and et al. Targeting Chk1 in p53-deficient triple-negative breast cancer is therapeutically beneficial in human-in-mouse tumor models J. Clin. Invest. 122 2012 1541 1552
169. M. Aarts, and et al. Forced mitotic entry of S-phase cells as a therapeutic strategy induced by inhibition of WEE1 Cancer Discov. 2 2012 524 539
170. Y. Dai, and et al. Pharmacological inhibitors of the mitogen-activated protein kinase (MAPK) kinase/MAPK cascade interact synergistically with UCN-01 to induce mitochondrial dysfunction and apoptosis in human leukemia cells Cancer Res. 61 2001 5106 5115
171. R. McKinstry, and et al. Inhibitors of MEK1/2 interact with UCN-01 to induce apoptosis and reduce colony formation in mammary and prostate carcinoma cells Cancer Biol. Ther. 1 2002 243 253
172. C. Mitchell, and et al. Poly(ADP-ribose) polymerase 1 modulates the lethality of CHK1 inhibitors in carcinoma cells Mol. Pharmacol. 78 2010 909 917
173. J. Murai, and et al. Trapping of PARP1 and PARP2 by clinical PARP inhibitors Cancer Res. 72 2012 5588 5599
174. T. Akiyama, and et al. G1 phase accumulation induced by UCN-01 is associated with dephosphorylation of Rb and CDK2 proteins as well as induction of CDK inhibitor p21/Cip1/WAF1/Sdi1 in p53-mutated human epidermoid carcinoma A431 cells Cancer Res. 57 1997 1495 1501
175. A. Konig, and et al. The novel cyclin-dependent kinase inhibitor flavopiridol downregulates Bcl-2 and induces growth arrest and apoptosis in chronic B-cell leukemia lines Blood 90 1997 4307 4312
176. S.J. McClue, and et al. In vitro and in vivo antitumor properties of the cyclin dependent kinase inhibitor CYC202 (R-roscovitine) Int. J. Cancer 102 2002 463 468
177. D. Horiuchi, and et al. MYC pathway activation in triple-negative breast cancer is synthetic lethal with CDK inhibition J. Exp. Med. 209 2012 679 696
178. S.R. Vora, and et al. CDK 4/6 inhibitors sensitize PIK3CA mutant breast cancer to PI3K inhibitors Cancer Cell 26 2014 136 149
179. I. Migliaccio, and et al. Cyclin-dependent kinase 4/6 inhibitors in breast cancer therapy Curr. Opin. Oncol. 26 2014 568 575
180. T.J. Robinson, and et al. RB1 status in triple negative breast cancer cells dictates response to radiation treatment and selective therapeutic drugs PLoS ONE 8 2013 e78641
181. J.L. Dean, and et al. Therapeutic response to CDK4/6 inhibition in breast cancer defined by ex vivo analyses of human tumors Cell Cycle 11 2012 2756 2761
182. A.K. McClendon, and et al. CDK4/6 inhibition antagonizes the cytotoxic response to anthracycline therapy Cell Cycle 11 2012 2747 2755
183. L.S. Symington, and J. Gautier Double-strand break end resection and repair pathway choice Annu. Rev. Genet. 45 2011 247 271
184. L.P. Ferretti, and et al. Controlling DNA-end resection: a new task for CDKs Front. Genet. 4 2013 99
185. N. Johnson, and et al. Compromised CDK1 activity sensitizes BRCA-proficient cancers to PARP inhibition Nat. Med. 17 2011 875 882
186. W.H. Fridman, and et al. Prognostic and predictive impact of intra- and peritumoral immune infiltrates Cancer Res. 71 2011 5601 5605
187. H. Matsumoto, and et al. Role of inflammatory infiltrates in triple negative breast cancer J. Clin. Pathol. 68 2015 506 510
188. G. Finak, and et al. Stromal gene expression predicts clinical outcome in breast cancer Nat. Med. 14 2008 518 527
189. S. Loi, and et al. Tumor infiltrating lymphocytes are prognostic in triple negative breast cancer and predictive for trastuzumab benefit in early breast cancer: results from the FinHER trial Ann. Oncol. 25 2014 1544 1550
190. + lymphocyte infiltration is an independent favorable prognostic indicator in basal-like breast cancer Breast Cancer Res. 14 2012 R48
191. E.M. Ibrahim, and et al. Risk of second breast cancer in female Hodgkin's lymphoma survivors: a meta-analysis BMC Cancer 12 2012 197
192. E.M. Ibrahim, and et al. The prognostic value of tumor-infiltrating lymphocytes in triple-negative breast cancer: a meta-analysis Breast Cancer Res. Treat. 148 2014 467 476
193. A.E. Teschendorff, and et al. Improved prognostic classification of breast cancer defined by antagonistic activation patterns of immune response pathway modules BMC Cancer 10 2010 604
194. A.E. Teschendorff, and et al. An immune response gene expression module identifies a good prognosis subtype in estrogen receptor negative breast cancer Genome Biol. 8 2007 R157
195. D.G. DeNardo, and et al. Leukocyte complexity predicts breast cancer survival and functionally regulates response to chemotherapy Cancer Discov. 1 2011 54 67
196. + lymphocytes predict clinical outcome in breast cancer J. Clin. Oncol. 29 2011 1949 1955
197. + lymphocytes are associated with cytotoxic immune responses and good clinical outcome in oestrogen receptor-negative breast cancer Br. J. Cancer 108 2013 155 162
198. S. Lee, and et al. Prognostic impact of FOXP3 expression in triple-negative breast cancer Acta Oncol. 52 2013 73 81
199. N.R. West, and et al. Tumor-infiltrating lymphocytes predict response to anthracycline-based chemotherapy in estrogen receptor-negative breast cancer Breast Cancer Res. 13 2011 R126
200. R. Yamaguchi, and et al. Tumor-infiltrating lymphocytes are important pathologic predictors for neoadjuvant chemotherapy in patients with breast cancer Hum. Pathol. 43 2012 1688 1694
201. S. Adams, and et al. Prognostic value of tumor-infiltrating lymphocytes in triple-negative breast cancers from two phase III randomized adjuvant breast cancer trials: ECOG 2197 and ECOG 1199 J. Clin. Oncol. 32 2014 2959 2966
202. S. Loi, and et al. Prognostic and predictive value of tumor-infiltrating lymphocytes in a phase III randomized adjuvant breast cancer trial in node-positive breast cancer comparing the addition of docetaxel to doxorubicin with doxorubicin-based chemotherapy: BIG 02-98 J. Clin. Oncol. 31 2013 860 867
203. C. Denkert, and et al. Tumor-associated lymphocytes as an independent predictor of response to neoadjuvant chemotherapy in breast cancer J. Clin. Oncol. 28 2010 105 113
204. E. Garcia-Martinez, and et al. Tumor-infiltrating immune cell profiles and their change after neoadjuvant chemotherapy predict response and prognosis of breast cancer Breast Cancer Res. 16 2014 488
205. M. Ono, and et al. Tumor-infiltrating lymphocytes are correlated with response to neoadjuvant chemotherapy in triple-negative breast cancer Breast Cancer Res. Treat. 132 2012 793 805
206. C. Denkert, and et al. Tumor-infiltrating lymphocytes and response to neoadjuvant chemotherapy with or without carboplatin in human epidermal growth factor receptor 2-positive and triple-negative primary breast cancers J. Clin. Oncol. 33 2015 983 991
207. J. Stagg, and B. Allard Immunotherapeutic approaches in triple-negative breast cancer: latest research and clinical prospects Ther. Adv. Med. Oncol. 5 2013 169 181
208. J.D. Wolchok, and et al. Nivolumab plus ipilimumab in advanced melanoma N. Engl. J. Med. 369 2013 122 133
209. T. Badovinac Crnjevic, and et al. High expression of MAGE-A10 cancer-testis antigen in triple-negative breast cancer Med. Oncol. 29 2012 1586 1591
210. G. Curigliano, and et al. Cancer-testis antigen expression in triple-negative breast cancer Ann. Oncol. 22 2011 98 103
211. at-Mage-b vaccine in correlation with improved T-cell responses in blood of a triple-negative breast cancer model 4T1 Cancer Med. 2 2013 571 582
212. V. Lakshminarayanan, and et al. Immune recognition of tumor-associated mucin MUC1 is achieved by a fully synthetic aberrantly glycosylated MUC1 tripartite vaccine Proc. Natl. Acad. Sci. U.S.A. 109 2012 261 266
213. N. Parinyanitikul, and et al. Mesothelin expression and survival outcomes in triple receptor negative breast cancer Clin. Breast Cancer 13 2013 378 384
214. J. Jacquemier, and et al. High expression of indoleamine 2,3-dioxygenase in the tumour is associated with medullary features and favourable outcome in basal-like breast carcinoma Int. J. Cancer 130 2012 96 104
215. K.A. Schalper PD-L1 expression and tumor-infiltrating lymphocytes: revisiting the antitumor immune response potential in breast cancer Oncoimmunology 3 2014 e29288
216. J.M. Taube, and et al. Association of PD-1, PD-1 ligands, and other features of the tumor immune microenvironment with response to anti-PD-1 therapy Clin. Cancer Res. 20 2014 5064 5074
217. S.L. Topalian, and et al. Survival, durable tumor remission, and long-term safety in patients with advanced melanoma receiving nivolumab J. Clin. Oncol. 32 2014 1020 1030
218. E.A. Mittendorf, and et al. PD-L1 expression in triple-negative breast cancer Cancer Immunol. Res. 2 2014 361 370
219. K.A. Schalper, and et al. In situ tumor PD-L1 mRNA expression is associated with increased TILs and better outcome in breast carcinomas Clin. Cancer Res. 20 2014 2773 2782
220. R. Sabatier, and et al. Prognostic and predictive value of PDL1 expression in breast cancer Oncotarget 6 2015 5449 5464
221. H. Wimberly, and et al. PD-L1 expression correlates with tumor-infiltrating lymphocytes and response to neoadjuvant chemotherapy in breast cancer Cancer Immunol. Res. 3 2015 326 332
222. S. Loi, and et al. CD73 promotes anthracycline resistance and poor prognosis in triple negative breast cancer Proc. Natl. Acad. Sci. U.S.A. 110 2013 11091 11096
223. D. Mittal, and et al. Antimetastatic effects of blocking PD-1 and the adenosine A2A receptor Cancer Res. 74 2014 3652 3658
224. B. Allard, and et al. Targeting CD73 enhances the antitumor activity of anti-PD-1 and anti-CTLA-4 mAbs Clin. Cancer Res. 19 2013 5626 5635
225. J.S. Logue, and D.K. Morrison Complexity in the signaling network: insights from the use of targeted inhibitors in cancer therapy Genes Dev. 26 2012 641 650
226. L.M. Ellis, and D.J. Hicklin Resistance to targeted therapies: refining anticancer therapy in the era of molecular oncology Clin. Cancer Res. 15 2009 7471 7478
227. C. Holohan, and et al. Cancer drug resistance: an evolving paradigm Nat. Rev. Cancer 13 2013 714 726
228. T.A. Yap, and et al. Development of therapeutic combinations targeting major cancer signaling pathways J. Clin. Oncol. 31 2013 1592 1605
229. L.M. Graves, and et al. The dynamic nature of the kinome Biochem. J. 450 2013 1 8
230. G. Hatzivassiliou, and et al. ERK inhibition overcomes acquired resistance to MEK inhibitors Mol. Cancer Ther. 11 2012 1143 1154
231. A.A. Midland, and et al. Defining the expressed breast cancer kinome Cell Res. 22 2012 620 623
232. X. Chen, and et al. XBP1 promotes triple-negative breast cancer by controlling the HIF1alpha pathway Nature 508 2014 103 107
233. S. Rottenberg, and 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. 105 2008 17079 17084
234. N. Johnson, and et al. Stabilization of mutant BRCA1 protein confers PARP inhibitor and platinum resistance Proc. Natl. Acad. Sci. U.S.A. 110 2013 17041 17046
235. C. Liu, and et al. A fine-scale dissection of the DNA double-strand break repair machinery and its implications for breast cancer therapy Nucleic Acids Res. 42 2014 6106 6127
236. J.E. Jaspers, and et al. Loss of 53BP1 causes PARP inhibitor resistance in Brca1-mutated mouse mammary tumors Cancer Discov. 3 2013 68 81
237. R. Ceccaldi, and et al. Homologous-recombination-deficient tumours are dependent on Poltheta-mediated repair Nature 518 2015 258 262
238. M.J. Lee, and et al. Sequential application of anticancer drugs enhances cell death by rewiring apoptotic signaling networks Cell 149 2012 780 794
239. E.J. Morris, and et al. Discovery of a novel ERK inhibitor with activity in models of acquired resistance to BRAF and MEK inhibitors Cancer Discov. 3 2013 742 750
240. T. Sandmann, and M. Boutros Screens, maps & networks: from genome sequences to personalized medicine Curr. Opin. Genet. Dev. 22 2012 36 44
241. S.K. Mishra, and et al. Computational cell fate modelling for discovery of rewiring in apoptotic network for enhanced cancer drug sensitivity BMC Syst. Biol. 9 Suppl. 1 2015 S4
242. M.K. Muellner, and et al. Targeting a cell state common to triple-negative breast cancers Mol. Syst. Biol. 11 2015 789
243. L.H. Pearl, and et al. Therapeutic opportunities within the DNA damage response Nat. Rev. Cancer 15 2015 166 180
244. A.L. Barabasi, and et al. Network medicine: a network-based approach to human disease Nat. Rev. Genet. 12 2011 56 68
245. A.E. Motter Improved network performance via antagonism: from synthetic rescues to multi-drug combinations Bioessays 32 2010 236 245
246. K. Yang, and et al. Finding multiple target optimal intervention in disease-related molecular network Mol. Syst. Biol. 4 2008 228
247. J.S. Parker, and et al. Supervised risk predictor of breast cancer based on intrinsic subtypes J. Clin. Oncol. 27 2009 1160 1167
248. ESMO Guidelines Working Group The ESMO Guidelines Working Group would like to publish the following corrections to manuscripts published in 2014 Ann. Oncol. 2015 10.1093/annonc/mdv204 Published online July 21, 2015
249. S.A. Eccles, and et al. Critical research gaps and translational priorities for the successful prevention and treatment of breast cancer Breast Cancer Res. 15 2013 R92