Emerging biomarkers in breast cancer care

Biomarkers in Medicine

Volumn 4, Issue 4, 2010, Pages 505-522

  Napieralski, Rudolf ^a   Brünner, Nils ^b   Mengele, Karin ^a   Schmitt, Manfred ^a  

^a TECHNICAL UNIVERSITY OF MUNICH   (Germany)

^b UNIVERSITY OF COPENHAGEN   (Denmark)

Author keywords

clinical utility; epigenetic marker; microarray analysis; miRNA; personalized cancer care; predictive impact; prognostic relevance; therapy

Indexed keywords

BIOLOGICAL MARKER; BONE MORPHOGENETIC PROTEIN 4; BRCA1 PROTEIN; CXCL9 CHEMOKINE; DNA TOPOISOMERASE (ATP HYDROLYSING); EPIDERMAL GROWTH FACTOR RECEPTOR 2; ESTROGEN RECEPTOR; FIBROBLAST GROWTH FACTOR 4; G PROTEIN COUPLED RECEPTOR 30; MICRORNA; PLASMINOGEN ACTIVATOR INHIBITOR; PROGESTERONE RECEPTOR; PROTEIN KINASE C DELTA; TISSUE INHIBITOR OF METALLOPROTEINASE 1; TOPOISOMERASE II ALPHA; TRANSCRIPTION FACTOR PITX2; UNCLASSIFIED DRUG; UROKINASE; Y BOX BINDING PROTEIN 1;

BREAST CANCER; CANCER RESEARCH; DNA METHYLATION; EPIGENETICS; GENE EXPRESSION; GENE TECHNOLOGY; GENETIC ASSOCIATION; HIGH RISK PATIENT; HUMAN; MICROARRAY ANALYSIS; PATIENT CARE; PATIENT CODING; PROGNOSIS; PROTEIN EXPRESSION; PROTEIN FUNCTION; REVIEW; RISK ASSESSMENT; TUMOR GENE; VALIDATION STUDY;

BREAST NEOPLASMS; HUMANS; TUMOR MARKERS, BIOLOGICAL;

EID: 77955624216     PISSN: 17520363     EISSN: None     Source Type: Journal    
DOI: 10.2217/bmm.10.73     Document Type: Review

References (243)

1. Schrohl AS, Holten-Andersen M, Sweep F et al.: Tumor markers: from laboratory to clinical utility. Mol. Cell Proteomics 2(6), 378-387 (2003)
2. Sawyers CL: The cancer biomarker problem. Nature 452(7187), 548-552 (2008)
3. McGuire WL: Breast cancer prognostic factors: evaluation guidelines. J. Natl Cancer Inst. 83(3), 154-155 (1991)
4. Schrohl AS, Wurtz S, Kohn E et al.: Banking of biological fluids for studies of disease-associated protein biomarkers. Mol. Cell Proteomics 7(10), 2061-2066 (2008)
5. Schmitt M, Mengele K, Schueren E et al.: European Organisation for Research and Treatment of Cancer (EORTC) Pathobiology Group standard operating procedure for the preparation of human tumour tissue extracts suited for the quantitative analysis of tissue-associated biomarkers. Eur. J. Cancer 43(5), 835-844 (2007)
6. Schmitt M, Harbeck N, Daidone MG et al.: Identification, validation, and clinical implementation of tumor-associated biomarkers to improve therapy concepts, survival, and quality of life of cancer patients: tasks of the Receptor and Biomarker Group of the European Organization for Research and Treatment of Cancer. Int. J. Oncol. 25(5), 1397-1406 (2004)
7. Hayes DF, Bast RC, Desch CE et al.: Tumor marker utility grading system: a framework to evaluate clinical utility of tumor markers. J. Natl Cancer Inst. 88(20), 1456-1466 (1996)
8. Simon RM, Paik S, Hayes DF: Use of archived specimens in evaluation of prognostic and predictive biomarkers. J. Natl Cancer Inst. 101(21), 1446-1452 (2009)
9. Montemurro F, Aglietta M: Hormone receptor-positive early breast cancer: controversies in the use of adjuvant chemotherapy. Endocr. Relat. Cancer 16(4), 1091-1102 (2009)
10. Dowsett M, Dunbier AK: Emerging biomarkers and new understanding of traditional markers in personalized therapy for breast cancer. Clin. Cancer Res. 14(24), 8019-8026 (2008
11. Sotiriou C, Piccart MJ: Taking gene-expression profiling to the clinic: when will molecular signatures become relevant to patient care? Nat. Rev. Cancer 7(7), 545-553 (2007)
12. Hinestrosa MC, Dickersin K, Klein P et al.: Shaping the future of biomarker research in breast cancer to ensure clinical relevance. Nat. Rev. Cancer 7(4), 309-315 (2007) (Pubitemid 46480973)
13. Harris L, Fritsche H, Mennel R et al.: American Society of Clinical Oncology 2007 update of recommendations for the use of tumor markers in breast cancer. J. Clin. Oncol. 25(33), 5287-5312 (2007)
14. Janicke F, Prechtl A, Thomssen C et al.: Randomized adjuvant chemotherapy trial in high-risk, lymph node-negative breast cancer patients identified by urokinase-type plasminogen activator and plasminogen activator inhibitor type 1. J. Natl Cancer Inst. 93(12), 913-920 (2001)
15. Look MP, van Putten WL, Duffy MJ et al.: 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(2), 116-128 (2002)
16. Ross JS, Slodkowska EA, Symmans WF et al.: The HER-2 receptor and breast cancer: ten years of targeted anti-HER-2 therapy and personalized medicine. Oncologist 14(4), 320-368 (2009)
17. Schechter AL, Stern DF, Vaidyanathan L et al.: The neu oncogene: an erb-B-related gene encoding a 185,000-Mr tumour antigen. Nature 312(5994), 513-516 (1984)
18. Perry CM, Wiseman LR: Trastuzumab. BioDrugs 12(2), 129-135 (1999)
19. Andreasen PA, Kjoller L, Christensen L, Duffy MJ: The urokinase-type plasminogen activator system in cancer metastasis: a review. Int. J. Cancer 72(1), 1-22 (1997)
20. Schmitt M, Wilhelm OG, Reuning U et al.: The urokinase plasminogen activator system as a novel target for tumour therapy. Fibrinol. Proteol. 14, 114-132 (2000)
21. Janicke F, Schmitt M, Ulm K, Gossner W, Graeff H: Urokinase-type plasminogen activator antigen and early relapse in breast cancer. Lancet 2(8670), 1049 (1989)
22. Janicke F, Schmitt M, Graeff H: Clinical relevance of the urokinase-type and tissue-type plasminogen activators and of their type 1 inhibitor in breast cancer. Semin. Thromb. Hemost. 17(3), 303-312 (1991)
23. Schmitt M, Harbeck N, Thomssen C et al.: Clinical impact of the plasminogen activation system in tumor invasion and metastasis: prognostic relevance and target for therapy. Thromb. Haemost. 78(1), 285-296 (1997)
24. Schmitt M, Mengele K, Gkazepis A et al.: Assessment of uPA (urokinase-type plasminogen activator) and its inhibitor PAI-1 in breast cancer tissue. Historical aspects and future prospects. Breast Care 3(Suppl. 2), 3-10 (2008)
25. Harbeck N, Kates RE, Schmitt M: Clinical relevance of invasion factors urokinase-type plasminogen activator and plasminogen activator inhibitor type 1 for individualized therapy decisions in primary breast cancer is greatest when used in combination. J. Clin. Oncol. 20(4), 1000-1007 (2002)
26. Konecny G, Untch M, Arboleda J et al.: Her-2/neu and urokinase-type plasminogen activator and its inhibitor in breast cancer. Clin. Cancer Res. 7(8), 2448-2457 (2001)
27. Bouchet C, Ferrero-Pous M, Hacene K, Becette V, Spyratos F: Limited prognostic value of c-erbB-2 compared to uPA and PAI-1 in primary breast carcinoma. Int. J. Biol. Markers 18(3), 207-217 (2003)
28. Zemzoum I, Kates RE, Ross JS et al.: Invasion factors uPA/PAI-1 and HER2 status provide independent and complementary information on patient outcome in node-negative breast cancer. J. Clin. Oncol. 21(6), 1022-1028 (2003)
29. Harbeck N, Schmitt M, Vetter M et al.: Prospective biomarker trials Chemo N0 and NNBC-3 Europe validate the clinical utility of invasion markers uPA and PAI-1 in node-negative breast cancer. Breast Care 3(Suppl. 2), 11-15 (2008)
30. Cardoso F, Bedard PL, Winer EP et al.: International guidelines for management of metastatic breast cancer: combination vs sequential single-agent chemotherapy. J. Natl Cancer Inst. 101(17), 1174-1181 (2009)
31. Piccart MJ, Sotiriou C, Cardoso F: New data on chemotherapy in the adjuvant setting. Breast 12(6), 373-378 (2003) (Pubitemid 38008646)
32. Colozza M, de Azambuja E, Personeni N et al.: Achievements in systemic therapies in the pregenomic era in metastatic breast cancer. Oncologist 12(3), 253-270 (2007)
33. Liu SV, Melstrom L, Yao K, Russell CA, Sener SF: Neoadjuvant therapy for breast cancer. J. Surg. Oncol. 101(4), 283-291 (2010)
34. Colleoni M, Viale G, Goldhirsch A: Lessons on responsiveness to adjuvant systemic therapies learned from the neoadjuvant setting. Breast 18(Suppl. 3), S137-S140 (2009)
35. Cummings J, Smyth JF: DNA topoisomerase I and II as targets for rational design of new anticancer drugs. Ann. Oncol. 4(7), 533-543 (1993)
36. Berger JM, Gamblin SJ, Harrison SC, Wang JC: Structure and mechanism of DNA topoisomerase II. Nature 379(6562), 225-232 (1996)
37. Kellner U, Sehested M, Jensen PB, Gieseler F, Rudolph P: Culprit and victim - DNA topoisomerase II. Lancet Oncol. 3(4), 235-243 (2002)
38. Di Leo A, Isola J, Piette F et al.: A meta-analysis of Phase III trials evaluating the predictive value of HER2 and topoisomerase IIa in early breast cancer patients treated with CMF or anthracycline-based adjuvant therapy. Br. Cancer Res. Treat. 107, 214 (2008)
39. Gennari A, Sormani MP, Pronzato P et al.: HER2 status and efficacy of adjuvant anthracyclines in early breast cancer: a pooled analysis of randomized trials. J. Natl Cancer Inst. 100(1), 14-20 (2008)
40. Dhesy-Thind B, Pritchard KI, Messersmith H et al.: HER2/neu in systemic therapy for women with breast cancer: a systematic review. Br. Cancer Res. Treat. 109(2), 209-229 (2008) (Pubitemid 351644854)
41. Di Leo A, Isola J, Piette F: A meta-analysis of Phase III trials evaluating the predictive value of HER2 and topoisomerase IIa in early breast cancer patients treated with CMF or anthracycline-based adjuvant therapy. Cancer Res. 69(2), 99S (2009)
42. Knoop AS, Knudsen H, Balslev E et al.: Retrospective analysis of topoisomerase IIa amplifications and deletions as predictive markers in primary breast cancer patients randomly assigned to cyclophosphamide, methotrexate, and fluorouracil or cyclophosphamide, epirubicin, and fluorouracil: Danish Breast Cancer Cooperative Group. J. Clin. Oncol. 23(30), 7483-7490 (2005)
43. Nielsen KV, Muller S, Moller S et al.: Aberrations of ERBB2 and TOP2A genes in breast cancer. Mol. Oncol. 4(2), 161-168 (2010)
44. Bartlett JM, Munro AF, Dunn JA et al.: Predictive markers of anthracycline benefit: a prospectively planned analysis of the UK National Epirubicin Adjuvant Trial (NEAT/BR9601). Lancet Oncol. 11(3), 266-274 (2010)
45. Pritchard KI: Are HER2 and TOP2A useful as prognostic or predictive biomarkers for anthracycline-based adjuvant chemotherapy for breast cancer? J. Clin. Oncol. 27(24), 3875-3876 (2009
46. Shpitz B, Bomstein Y, Zehavi T et al.: Topoisomerase IIa expression in ductal carcinoma in situ of the breast: a preliminary study. Hum. Pathol. 31(10), 1249-1254 (2000)
47. Smith K, Houlbrook S, Greenall M, Carmichael J, Harris AL: Topoisomerase IIa co-amplification with erbB2 in human primary breast cancer and breast cancer cell lines: relationship to m-AMSA and mitoxantrone sensitivity. Oncogene 8(4), 933-938 (1993)
48. Nakopoulou L, Lazaris AC, Kavantzas N et al.: DNA topoisomerase IIa immunoreactivity as a marker of tumor aggressiveness in invasive breast cancer. Pathobiology 68(3), 137-143 (2000)
49. Durbecq V, Desmed C, Paesmans M et al.: Correlation between topoisomerase-IIa gene amplification and protein expression in HER-2 amplified breast cancer. Int. J. Oncol. 25(5), 1473-1479 (2004)
50. Davidsen ML, Wurtz SO, Romer MU et al.: TIMP-1 gene deficiency increases tumour cell sensitivity to chemotherapy-induced apoptosis. Br. J. Cancer 95(8), 1114-1120 (2006)
51. Willemoe GL, Hertel PB, Bartels A et al.: Lack of TIMP-1 tumour cell immunoreactivity predicts effect of adjuvant anthracycline-based chemotherapy in patients (n = 647) with primary breast cancer. A Danish Breast Cancer Cooperative Group Study. Eur. J. Cancer 45(14), 2528-2536 (2009)
52. Ejlertsen B, Jensen MB, Nielsen KV et al.: HER2, TOP2A, and TIMP-1 and responsiveness to adjuvant anthracycline-containing chemotherapy in high-risk breast cancer patients. J. Clin. Oncol. 28(6), 984-990 (2010)
53. Hernandez-Vargas H, Palacios J, Moreno-Bueno G: Telling cells how to die: docetaxel therapy in cancer cell lines. Cell Cycle 6(7), 780-783 (2007)
54. Pusztai L: Markers predicting clinical benefit in breast cancer from microtubule-targeting agents. Ann. Oncol. 18(Suppl. 12), XII15- XII20 (2007)
55. Rouzier R, Rajan R, Wagner P et al.: Microtubule-associated protein tau: a marker of paclitaxel sensitivity in breast cancer. Proc. Natl Acad. Sci. USA 102(23), 8315-8320 (2005)
56. Pusztai L, Jeong JH, Gong Y et al.: Evaluation of microtubule-associated protein-tau expression as a prognostic and predictive marker in the NSABP-B 28 randomized clinical trial. J. Clin. Oncol. 27(26), 4287-4292 (2009)
57. Assaraf YG: Molecular basis of antifolate resistance. Cancer Metastasis Rev. 26(1), 153-181 (2007)
58. Tsunoda Y, Suzuki K, Tsunoda A, Takimoto M, Kusano M: Evaluation of 5-fluorouracil related genes in breast cancer to predict the effect of adjuvant therapy with oral fluorouracil derivatives. Oncol. Rep. 23(3), 771-777 (2010)
59. Wyatt MD, Wilson DM 3rd: Participation of DNA repair in the response to 5-fluorouracil. Cell. Mol. Life Sci. 66(5), 788-799 (2009)
60. Specht K, Harbeck N, Smida J et al.: Expression profiling identifies genes that predict recurrence of breast cancer after adjuvant CMF-based chemotherapy. Br. Cancer Res. Treat. 118(1), 45-56 (2009)
61. Fulton AM: The chemokine receptors CXCR4 and CXCR3 in cancer. Curr. Oncol. Rep. 11(2), 125-131 (2009)
62. Denkert C, Loibl S, Noske A et al.: Tumor-associated lymphocytes as an independent predictor of response to neoadjuvant chemotherapy in breast cancer. J. Clin. Oncol. 28(1), 105-113 (2010)
63. Dahl E, En-Nia A, Wiesmann F et al.: Nuclear detection of Y-box protein-1 (YB-1) closely associates with progesterone receptor negativity and is a strong adverse survival factor in human breast cancer. BMC Cancer. 9, 410 (2009)
64. Janz M, Harbeck N, Dettmar P et al.: Y-box factor YB-1 predicts drug resistance and patient outcome in breast cancer independent of clinically relevant tumor biologic factors HER2, uPA and PAI-1. Int. J. Cancer 97(3), 278-282 (2002)
65. Fujii T, Kawahara A, Basaki Y et al.: Expression of HER2 and estrogen receptor a depends upon nuclear localization of Y-box binding protein-1 in human breast cancers. Cancer Res. 68(5), 1504-1512 (2008)
66. Gluz O, Mengele K, Schmitt M et al.: Y-box-binding protein YB-1 identifies high-risk patients with primary breast cancer benefiting from rapidly cycled tandem high-dose adjuvant chemotherapy. J. Clin. Oncol. 27(36), 6144-6151 (2009)
67. Bargou RC, Jurchott K, Wagener C et al.: Nuclear localization and increased levels of transcription factor YB-1 in primary human breast cancers are associated with intrinsic MDR1 gene expression. Nat. Med. 3(4), 447-450 (1997)
68. Kohno K, Izumi H, Uchiumi T, Ashizuka M, Kuwano M: The pleiotropic functions of the Y-box-binding protein, YB-1. Bioessays 25(7), 691-698 (2003)
69. Berquin IM, Pang B, Dziubinski ML et al.: Y-box-binding protein 1 confers EGF independence to human mammary epithelial cells. Oncogene 24(19), 3177-3186 (2005)
70. Evdokimova V, Ruzanov P, Anglesio MS et al.: Akt-mediated YB-1 phosphorylation activates translation of silent mRNA species. Mol. Cell Biol. 26(1), 277-292 (2006)
71. Kohno Y, Matsuki Y, Tanimoto A et al.: Expression of Y-box-binding protein dbpC/ contrin, a potentially new cancer/testis antigen. Br. J. Cancer 94(5), 710-716 (2006)
72. Yasen M, Kajino K, Kano S et al.: The up-regulation of Y-box binding proteins (DNA binding protein A and Y-box binding protein-1) as prognostic markers of hepatocellular carcinoma. Clin. Cancer Res. 11(20), 7354-7361 (2005
73. Wang GR, Zheng Y, Che XM et al.: Upregulation of human DNA binding protein A (dbpA) in gastric cancer cells. Acta Pharmacol. Sin. 30(10), 1436-1442 (2009)
74. Toh S, Nakamura T, Ohga T et al.: Genomic organization of the human Y-box protein (YB-1) gene. Gene 206(1), 93-97 (1998)
75. Jurchott K, Bergmann S, Stein U et al.: YB-1 as a cell cycle-regulated transcription factor facilitating cyclin A and cyclin B1 gene expression. J. Biol. Chem. 278(30), 27988-27996 (2003)
76. Schittek B, Psenner K, Sauer B et al.: The increased expression of Y box-binding protein 1 in melanoma stimulates proliferation and tumor invasion, antagonizes apoptosis and enhances chemoresistance. Int. J. Cancer 120(10), 2110-2118 (2007)
77. Basaki Y, Hosoi F, Oda Y et al.: Akt-dependent nuclear localization of Y-box-binding protein 1 in acquisition of malignant characteristics by human ovarian cancer cells. Oncogene 26(19), 2736-2746 (2007)
78. Evdokimova V, Tognon C, Ng T et al.: Translational activation of snail1 and other developmentally regulated transcription factors by YB-1 promotes an epithelial-mesenchymal transition. Cancer Cell 15(5), 402-415 (2009)
79. Wu J, Lee C, Yokom D et al.: Disruption of the Y-box binding protein-1 results in suppression of the epidermal growth factor receptor and HER-2. Cancer Res. 66(9), 4872-4879 (2006)
80. Samuel S, Beifuss KK, Bernstein LR: YB-1 binds to the MMP-13 promoter sequence and represses MMP-13 transactivation via the AP-1 site. Biochim. Biophys. Acta 1769(9-10), 525-531 (2007)
81. Huang J, Tan PH, Li KB et al.: Y-box binding protein, YB-1, as a marker of tumor aggressiveness and response to adjuvant chemotherapy in breast cancer. Int. J. Oncol. 26(3), 607-613 (2005)
82. Fujita T, Ito K, Izumi H et al.: Increased nuclear localization of transcription factor Y-box binding protein 1 accompanied by up-regulation of P-glycoprotein in breast cancer pretreated with paclitaxel. Clin. Cancer Res. 11(24 Pt 1), 8837-8844 (2005)
83. Habibi G, Leung S, Law JH et al.: Redefining prognostic factors for breast cancer: YB-1 is a stronger predictor of relapse and disease-specific survival than estrogen receptor or HER-2 across all tumor subtypes. Breast Cancer Res. 10(5), R86 (2008)
84. Filardo EJ, Quinn JA, Sabo E: Association of the membrane estrogen receptor, GPR30, with breast tumor metastasis and transactivation of the epidermal growth factor receptor. Steroids 73(9-10), 870-873 (2008)
85. Filardo EJ, Thomas P: GPR30: a seven-transmembrane-spanning estrogen receptor that triggers EGF release. Trends Endocrinol. Metab. 16(8), 362-367 (2005)
86. Filardo EJ, Graeber CT, Quinn JA et al.: Distribution of GPR30, a seven membrane-spanning estrogen receptor, in primary breast cancer and its association with clinicopathologic determinants of tumor progression. Clin. Cancer Res. 12(21), 6359-6366 (2006)
87. Ng EK, Wong CL, Ma ES, Kwong A: MicroRNAs as new players for diagnosis, prognosis, and therapeutic targets in breast cancer. J. Oncol. 305, 420 (2009)
88. Wijnhoven BP, Michael MZ, Watson DI: MicroRNAs and cancer. Br. J. Surg. 94(1), 23-30 (2007)
89. Esquela-Kerscher A, Slack FJ: Oncomirs - microRNAs with a role in cancer. Nat. Rev. Cancer 6(4), 259-269 (2006)
90. Smith DD, Saetrom P, Snove O Jr et al.: Meta-analysis of breast cancer microarray studies in conjunction with conserved cis-elements suggest patterns for coordinate regulation. BMC Bioinformatics 9, 63 (2008)
91. ODay E, Lal A: MicroRNAs and their target gene networks in breast cancer. Breast Cancer Res. 12(2), 201 (2010)
92. Lowery AJ, Miller N, Devaney A et al.: MicroRNA signatures predict oestrogen receptor, progesterone receptor and HER2/neu receptor status in breast cancer. Breast Cancer Res. 11(3), R27 (2009)
93. Shi M, Guo N: MicroRNA expression and its implications for the diagnosis and therapeutic strategies of breast cancer. Cancer Treat. Rev. 35(4), 328-334 (2009)
94. Cheng C, Fu X, Alves P, Gerstein M: mRNA expression profiles show differential regulatory effects of microRNAs between estrogen receptor-positive and estrogen receptor-negative breast cancer. Genome Biol. 10(9), R90 (2009)
95. Foekens JA, Sieuwerts AM, Smid M et al.: Four miRNAs associated with aggressiveness of lymph node-negative, estrogen receptor-positive human breast cancer. Proc. Natl Acad. Sci. USA 105(35), 13021-13026 (2008)
96. Liu S, Goldstein RH, Scepansky EM, Rosenblatt M: Inhibition of rho-associated kinase signaling prevents breast cancer metastasis to human bone. Cancer Res. 69(22), 8742-8751 (2009)
97. Baffa R, Fassan M, Volinia S et al.: MicroRNA expression profiling of human metastatic cancers identifies cancer gene targets. J. Pathol. 219(2), 214-221 (2009)
98. Grelier G, Voirin N, Ay AS et al.: Prognostic value of Dicer expression in human breast cancers and association with the mesenchymal phenotype. Br. J. Cancer 101(4), 673-683 (2009)
99. Yan LX, Huang XF, Shao Q et al.: MicroRNA miR-21 overexpression in human breast cancer is associated with advanced clinical stage, lymph node metastasis and patient poor prognosis. RNA 14(11), 2348-2360 (2008)
100. Heneghan HM, Miller N, Lowery AJ et al.: Circulating microRNAs as novel minimally invasive biomarkers for breast cancer. Ann. Surg. 251(3), 499-505 (2010)
101. Qian B, Katsaros D, Lu L et al.: High miR-21 expression in breast cancer associated with poor disease-free survival in early stage disease and high TGF-b1. Br. Cancer Res. Treat. 117(1), 131-140 (2009)
102. Camps C, Buffa FM, Colella S et al.: hsa-miR-210 is induced by hypoxia and is an independent prognostic factor in breast cancer. Clin. Cancer Res. 14(5), 1340-1348 (2008)
103. Liang Z, Wu H, Xia J et al.: Involvement of miR-326 in chemotherapy resistance of breast cancer through modulating expression of multidrug resistance-associated protein 1. Biochem. Pharmacol. 79(6), 817-824 (2010)
104. Salter KH, Acharya CR, Walters KS et al.: An integrated approach to the prediction of chemotherapeutic response in patients with breast cancer. PLoS ONE 3(4), e1908 (2008)
105. Zhao JJ, Lin J, Yang H et al.: MicroRNA-221/222 negatively regulates estrogen receptor a and is associated with tamoxifen resistance in breast cancer. J. Biol. Chem. 283(45), 31079-31086 (2008)
106. Miller TE, Ghoshal K, Ramaswamy B et al.: MicroRNA-221/222 confers tamoxifen resistance in breast cancer by targeting p27Kip1. J. Biol. Chem. 283(44), 29897-29903 (2008)
107. Xin F, Li M, Balch C et al.: Computational analysis of microRNA profiles and their target genes suggests significant involvement in breast cancer antiestrogen resistance. Bioinformatics 25(4), 430-434 (2009)
108. Masri S, Phung S, Wang X, Chen S: Molecular characterization of aromatase inhibitor-resistant, tamoxifen-resistant and LTEDaro cell lines. J. Steroid Biochem. Mol. Biol. 118(4-5), 277-282 (2010)
109. Zhou M, Liu Z, Zhao Y et al.: MicroRNA- 125b confers the resistance of breast cancer cells to paclitaxel through suppression of pro-apoptotic Bcl-2 antagonist killer 1 (Bak1). J. Biol. Chem. 285(28), 21496-21507 (2010
110. Mei M, Ren Y, Zhou X et al.: Downregulation of miR-21 enhances chemotherapeutic effect of taxol in breast carcinoma cells. Technol. Cancer Res. Treat. 9(1), 77-86 (2010)
111. Cui XY, Guo YJ, Yao HR: [Analysis of microRNA in drug-resistant breast cancer cell line MCF-7/ADR]. Nan. Fang. Yi Ke Da Xue Xue Bao 28(10), 1813-1815 (2008)
112. Chen GQ, Zhao ZW, Zhou HY, Liu YJ, Yang HJ: Systematic analysis of microRNA involved in resistance of the MCF-7 human breast cancer cell to doxorubicin. Med. Oncol. 27(2), 406-415 (2010)
113. Kovalchuk O, Filkowski J, Meservy J et al.: Involvement of microRNA-451 in resistance of the MCF-7 breast cancer cells to chemotherapeutic drug doxorubicin. Mol. Cancer Ther. 7(7), 2152-2159 (2008)
114. Pogribny IP, Filkowski JN, Tryndyak VP et al.: Alterations of microRNAs and their targets are associated with acquired resistance of MCF-7 breast cancer cells to cisplatin. Int. J. Cancer (2010) (Epub ahead print)
115. Ma L, Reinhardt F, Pan E et al.: Therapeutic silencing of miR-10b inhibits metastasis in a mouse mammary tumor model. Nat. Biotechnol. 28(4), 341-347 (2010)
116. Barh D, Malhotra R, Ravi B, Sindhurani P: MicroRNA let-7: an emerging next-generation cancer therapeutic. Curr. Oncol. 17(1), 70-80 (2010)
117. Brown R, Strathdee G: Epigenomics and epigenetic therapy of cancer. Trends Mol. Med. 8(Suppl. 4), S43-S48 (2002)
118. Martens JW, Margossian AL, Schmitt M, Foekens J, Harbeck N: DNA methylation as a biomarker in breast cancer. Future Oncol. 5(8), 1245-1256 (2009)
119. Reijm EA, Jansen MP, Ruigrok-Ritstier K et al.: Decreased expression of EZH2 is associated with upregulation of ER and favorable outcome to tamoxifen in advanced breast cancer. Br. Cancer Res. Treat. (2010) (Epub ahead of print)
120. Wei Y, Xia W, Zhang Z et al.: Loss of trimethylation at lysine 27 of histone H3 is a predictor of poor outcome in breast, ovarian, and pancreatic cancers. Mol. Carcinog. 47(9), 701-706 (2008)
121. Elsheikh SE, Green AR, Rakha EA et al.: Global histone modifications in breast cancer correlate with tumor phenotypes, prognostic factors, and patient outcome. Cancer Res. 69(9), 3802-3809 (2009)
122. Widschwendter M, Apostolidou S, Raum E et al.: Epigenotyping in peripheral blood cell DNA and breast cancer risk: a proof of principle study. PLoS ONE 3(7), e2656 (2008)
123. Fiegl H, Millinger S, Goebel G et al.: Breast cancer DNA methylation profiles in cancer cells and tumor stroma: association with HER-2/neu status in primary breast cancer. Cancer Res. 66(1), 29-33 (2006)
124. Terada K, Okochi-Takada E, Akashi-Tanaka S et al.: Association between frequent CpG island methylation and HER2 amplification in human breast cancers. Carcinogenesis 30(3), 466-471 (2009)
125. Melnikov AA, Scholtens DM, Wiley EL, Khan SA, Levenson VV: Array-based multiplex analysis of DNA methylation in breast cancer tissues. J. Mol. Diagn. 10(1), 93-101 (2008)
126. Zou D, Yoon HS, Perez D et al.: Epigenetic silencing in non-neoplastic epithelia identifies E-cadherin (CDH1) as a target for chemoprevention of lobular neoplasia. J. Pathol. 218(2), 265-272 (2009)
127. Van der Auwera I, Van Laere SJ, Van den Bosch SM et al.: Aberrant methylation of the adenomatous polyposis coli (APC) gene promoter is associated with the inflammatory breast cancer phenotype. Br. J. Cancer 99(10), 1735-1742 (2008)
128. Fiegl H, Jones A, Hauser-Kronberger C et al.: Methylated NEUROD1 promoter is a marker for chemosensitivity in breast cancer. Clin. Cancer Res. 14(11), 3494-3502 (2008)
129. Fiegl H, Millinger S, Mueller-Holzner E et al.: Circulating tumor-specific DNA: a marker for monitoring efficacy of adjuvant therapy in cancer patients. Cancer Res. 65(4), 1141-1145 (2005)
130. Muller HM, Fiegl H, Widschwendter A, Widschwendter M: Prognostic DNA methylation marker in serum of cancer patients. Ann. NY Acad. Sci. 1022, 44-49 (2004) (Pubitemid 38951580)
131. Widschwendter M, Siegmund KD, Muller HM et al.: Association of breast cancer DNA methylation profiles with hormone receptor status and response to tamoxifen. Cancer Res. 64(11), 3807-3813 (2004)
132. Locke I, Kote-Jarai Z, Fackler MJ et al.: Gene promoter hypermethylation in ductal lavage fluid from healthy BRCA gene mutation carriers and mutation-negative controls. Breast Cancer Res. 9(1), R20 (2007)
133. Sadr-Nabavi A, Ramser J, Volkmann J et al.: Decreased expression of angiogenesis antagonist EFEMP1 in sporadic breast cancer is caused by aberrant promoter methylation and points to an impact of EFEMP1 as molecular biomarker. Int. J. Cancer 124(7), 1727-1735 (2009)
134. Chen L, Zhu Z, Sun X et al.: Down-regulation of tumor suppressor gene FEZ1/ LZTS1 in breast carcinoma involves promoter methylation and associates with metastasis. Br. Cancer Res. Treat. 116(3), 471-478 (2009)
135. Silva JM, Garcia JM, Dominguez G et al.: Persistence of tumor DNA in plasma of breast cancer patients after mastectomy. Ann. Surg. Oncol. 9(1), 71-76 (2002)
136. Krusche CA, Wulfing P, Kersting C et al.: Histone deacetylase-1 and -3 protein expression in human breast cancer: a tissue microarray analysis. Br. Cancer Res. Treat. 90(1), 15-23 (2005)
137. Zhang Z, Yamashita H, Toyama T et al.: Quantitation of HDAC1 mRNA expression in invasive carcinoma of the breast. Br. Cancer Res. Treat. 94(1), 11-16 (2005)
138. Hartmann O, Spyratos F, Harbeck N et al.: DNA methylation markers predict outcome in node-positive, estrogen receptor-positive breast cancer with adjuvant anthracycline-based chemotherapy. Clin. Cancer Res. 15(1), 315-323 (2009)
139. Nimmrich I, Sieuwerts AM, Meijer-van Gelder ME et al.: DNA hypermethylation of PITX2 is a marker of poor prognosis in untreated lymph node-negative hormone receptor-positive breast cancer patients. Br. Cancer Res. Treat. 111(3), 429-437 (2008)
140. Harbeck N, Nimmrich I, Hartmann A et al.: Multicenter study using paraffin-embedded tumor tissue testing PITX2 DNA methylation as a marker for outcome prediction in tamoxifen-treated, node-negative breast cancer patients. J. Clin. Oncol. 26(31), 5036-5042 (2008)
141. Maier S, Nimmrich I, Koenig T et al.: DNA-methylation of the homeodomain transcription factor PITX2 reliably predicts risk of distant disease recurrence in tamoxifen-treated, node-negative breast cancer patients - technical and clinical validation in a multi-centre setting in collaboration with the European Organisation for Research and Treatment of Cancer (EORTC) PathoBiology group. Eur. J. Cancer 43(11), 1679-1686 (2007)
142. Boorman CJ, Shimeld SM: The evolution of left-right asymmetry in chordates. Bioessays 24(11), 1004-1011 (2002)
143. Hjalt TA, Semina EV, Amendt BA, Murray JC: The Pitx2 protein in mouse development. Dev. Dyn. 218(1), 195-200 (2000)
144. Kumar S, Duester G: Retinoic acid signaling in perioptic mesenchyme represses Wnt signaling via induction of Pitx2 and Dkk2. Dev. Biol. 340(1), 67-74 (2010)
145. Sohn KC, Shi G, Jang S et al.: Pitx2, a b-catenin-regulated transcription factor, regulates the differentiation of outer root sheath cells cultured in vitro. J. Dermatol. Sci. 54(1), 6-11 (2009)
146. Briata P, Ilengo C, Corte G et al.: The Wnt/b-catenin→ Pitx2 pathway controls the turnover of Pitx2 and other unstable mRNAs. Mol Cell. 12(5), 1201-1211 (2003)
147. Kioussi C, Briata P, Baek SH et al.: Identification of a Wnt/Dvl/b-Catenin→ Pitx2 pathway mediating cell-type-specific proliferation during development. Cell 111(5), 673-685 (2002)
148. Suszko MI, Antenos M, Balkin DM, Woodruff TK: Smad3 and Pitx2 cooperate in stimulation of FSHb gene transcription. Mol. Cell Endocrinol. 281(1-2), 27-36 (2008)
149. Yost HJ: Establishment of left-right asymmetry. Int. Rev. Cytol. 203, 357-381 (2001)
150. Constam DB, Robertson EJ: SPC4/PACE4 regulates a TGFb signaling network during axis formation. Genes Dev. 14(9), 1146-1155 (2000)
151. Chang H, Zwijsen A, Vogel H, Huylebroeck D, Matzuk MM: Smad5 is essential for left-right asymmetry in mice. Dev. Biol. 219(1), 71-78 (2000)
152. Nudi M, Ouimette JF, Drouin J: Bone morphogenic protein (Smad)-mediated repression of proopiomelanocortin transcription by interference with Pitx/Tpit activity. Mol. Endocrinol. 19(5), 1329-1342 (2005)
153. Simard A, Di Giorgio L, Amen M et al.: The Pitx2c N-terminal domain is a critical interaction domain required for asymmetric morphogenesis. Dev. Dyn. 238(10), 2459-2470 (2009)
154. Huang Y, Huang K, Boskovic G et al.: Proteomic and genomic analysis of PITX2 interacting and regulating networks. FEBS Lett. 583(4), 638-642 (2009)
155. Lavery K, Swain P, Falb D, Alaoui-Ismaili MH: BMP-2/4 and BMP-6/7 differentially utilize cell surface receptors to induce osteoblastic differentiation of human bone marrow-derived mesenchymal stem cells. J. Biol. Chem. 283(30), 20948-20958 (2008)
156. Maeda S, Hayashi M, Komiya S, Imamura T, Miyazono K: Endogenous TGF-b signaling suppresses maturation of osteoblastic mesenchymal cells. EMBO J. 23(3), 552-563 (2004)
157. Chang SF, Chang TK, Peng HH et al.: BMP-4 induction of arrest and differentiation of osteoblast-like cells via p21 CIP1 and p27 KIP1 regulation. Mol. Endocrinol. 23(11), 1827-1838 (2009)
158. Bakrania P, Efthymiou M, Klein JC et al.: Mutations in BMP4 cause eye, brain, and digit developmental anomalies: overlap between the BMP4 and hedgehog signaling pathways. Am. J. Hum. Genet. 82(2), 304-319 (2008)
159. Hutton JF, Rozenkov V, Khor FS, DAndrea RJ, Lewis ID: Bone morphogenetic protein 4 contributes to the maintenance of primitive cord blood hematopoietic progenitors in an ex vivo stroma-noncontact co-culture system. Stem Cells Dev. 15(6), 805-813 (2006)
160. McCullough KA, Waits CA, Garimella R et al.: Immunohistochemical localization of bone morphogenetic proteins (BMPs) 2, 4, 6, and 7 during induced heterotopic bone formation. J. Orthop. Res. 25(4), 465-472 (2007)
161. Kelly MA, Hirschi KK: Signaling hierarchy regulating human endothelial cell development. Arterioscler. Thromb. Vasc. Biol. 29(5), 718-724 (2009)
162. Alarmo EL, Kuukasjarvi T, Karhu R, Kallioniemi A: A comprehensive expression survey of bone morphogenetic proteins in breast cancer highlights the importance of BMP4 and BMP7. Br. Cancer Res. Treat. 103(2), 239-246 (2007)
163. Deng H, Makizumi R, Ravikumar TS et al.: Bone morphogenetic protein-4 is overexpressed in colonic adenocarcinomas and promotes migration and invasion of HCT116 cells. Exp. Cell. Res. 313(5), 1033-1044 (2007)
164. Mancino M, Strizzi L, Wechselberger C et al.: Regulation of human Cripto-1 gene expression by TGF-b1 and BMP-4 in embryonal and colon cancer cells. J. Cell Physiol. 215(1), 192-203 (2008)
165. Virdi AS, Cook LJ, Oreffo RO, Triffitt JT: Modulation of bone morphogenetic protein-2 and bone morphogenetic protein-4 gene expression in osteoblastic cell lines. Cell Mol. Biol. 44(8), 1237-1246 (1998)
166. Theriault BL, Shepherd TG, Mujoomdar ML, Nachtigal MW: BMP4 induces EMT and Rho GTPase activation in human ovarian cancer cells. Carcinogenesis 28(6), 1153-1162 (2007)
167. Feeley BT, Krenek L, Liu N et al.: Overexpression of noggin inhibits BMP-mediated growth of osteolytic prostate cancer lesions. Bone 38(2), 154-166 (2006)
168. Rappolee DA, Basilico C, Patel Y, Werb Z: Expression and function of FGF-4 in peri-implantation development in mouse embryos. Development 120(8), 2259-2269 (1994)
169. Bobick BE, Thornhill TM, Kulyk WM: Fibroblast growth factors 2, 4, and 8 exert both negative and positive effects on limb, frontonasal, and mandibular
170. Zhang X, Ibrahimi OA, Olsen SK et al.: Receptor specificity of the fibroblast growth factor family. The complete mammalian FGF family. J. Biol. Chem. 281(23), 15694-15700 (2006)
171. Meijer D, Sieuwerts AM, Look MP et al.: Fibroblast growth factor receptor 4 predicts failure on tamoxifen therapy in patients with recurrent breast cancer. Endocr. Relat. Cancer. 15(1), 101-111 (2008)
172. Kiuru-Kuhlefelt S, Sarlomo-Rikala M, Larramendy ML et al.: FGF4 and INT2 oncogenes are amplified and expressed in Kaposis sarcoma. Mod. Pathol. 13(4), 433-437 (2000)
173. Suzuki K, Tokue A, Kamiakito T et al.: Predominant expression of fibroblast growth factor (FGF)8, FGF4, and FGF receptor 1 in nonseminomatous and highly proliferative components of testicular germ cell tumors. Virchows Arch. 439(5), 616-621 (2001)
174. Maerz WJ, Baselga J, Reuter VE et al.: FGF4 dissociates anti-tumorigenic from differentiation signals of retinoic acid in human embryonal carcinomas. Oncogene 17(6), 761-767 (1998)
175. Shimon I, Huttner A, Said J, Spirina OM, Melmed S: Heparin-binding secretory transforming gene (hst) facilitates rat lactotrope cell tumorigenesis and induces prolactin gene transcription. J. Clin. Invest. 97(1), 187-195 (1996)
176. Gurlek A, Karavitaki N, Ansorge O, Wass JA: What are the markers of aggressiveness in prolactinomas? Changes in cell biology, extracellular matrix components, angiogenesis and genetics. Eur. J. Endocrinol. 156(2), 143-153 (2007)
177. Hui AB, Lo KW, Teo PM, To KF, Huang DP: Genome wide detection of oncogene amplifications in nasopharyngeal carcinoma by array based comparative genomic hybridization. Int. J. Oncol. 20(3), 467-473 (2002)
178. Oliver RT: Germ cell cancer. Curr. Opin. Oncol. 11(3), 236-241 (1999)
179. Carneiro A, Isinger A, Karlsson A et al.: Prognostic impact of array-based genomic profiles in esophageal squamous cell cancer. BMC Cancer 8, 98 (2008)
180. Sugimura T, Yoshida T, Sakamoto H et al.: Molecular biology of the hst-1 gene. Ciba Found Symp. 150, 79-89; discussion 89-98 (1990)
181. Rodrigo JP, Suarez C, Gonzalez MV et al.: Variability of genetic alterations in different sites of head and neck cancer. Laryngoscope 111(7), 1297-1301 (2001)
182. Takeo S, Arai H, Kusano N et al.: Examination of oncogene amplification by genomic DNA microarray in hepatocellular carcinomas: comparison with comparative genomic hybridization analysis. Cancer Genet. Cytogenet. 130(2), 127-132 (2001)
183. Lazar V, Ecsedi S, Szollosi AG et al.: Characterization of candidate gene copy number alterations in the 11q13 region along with BRAF and NRAS mutations in human melanoma. Mod. Pathol. 22(10), 1367-1378 (2009)
184. Hauge H, Patzke S, Aasheim HC: Characterization of the FAM110 gene family. Genomics 90(1), 14-27 (2007)
185. Wu C, Ma MH, Brown KR et al.: Systematic identification of SH3 domain-mediated human protein-protein interactions by peptide array target screening. Proteomics 7(11), 1775-1785 (2007)
186. Martens JW, Nimmrich I, Koenig T et al.: Association of DNA methylation of phosphoserine aminotransferase with response to endocrine therapy in patients with recurrent breast cancer. Cancer Res. 65(10), 4101-4117 (2005)
187. Basurko MJ, Marche M, Darriet M, Cassaigne A: Phosphoserine aminotransferase, the second step-catalyzing enzyme for serine biosynthesis. IUBMB Life 48(5), 525-529 (1999)
188. Pollari S, Kakonen SM, Edgren H et al.: Enhanced serine production by bone metastatic breast cancer cells stimulates osteoclastogenesis. Br. Cancer Res. Treat. (2010) (Epub ahead of print)
189. Golouh R, Cufer T, Sadikov A et al.: The prognostic value of Stathmin-1, S100A2, and SYK proteins in ER-positive primary breast cancer patients treated with adjuvant tamoxifen monotherapy: an immunohistochemical study. Br. Cancer Res. Treat. 110(2), 317-326 (2008)
190. Nalapareddy K, Jiang H, Guachalla Gutierrez LM, Rudolph KL: Determining the influence of telomere dysfunction and DNA damage on stem and progenitor cell aging: what markers can we use? Exp. Gerontol. 43(11), 998-1004 (2008)
191. Alli E, Yang JM, Ford JM, Hait WN: Reversal of stathmin-mediated resistance to paclitaxel and vinblastine in human breast carcinoma cells. Mol. Pharmacol. 71(5), 1233-1240 (2007)
192. Campone M, Campion L, Roche H et al.: Prediction of metastatic relapse in node-positive breast cancer: establishment of a clinicogenomic model after FEC100 adjuvant regimen. Br. Cancer Res. Treat. 109(3), 491-501 (2008)
193. Oishi Y, Nagasaki K, Miyata S et al.: Functional pathway characterized by gene expression analysis of supraclavicular lymph node metastasis-positive breast cancer. J. Hum. Genet. 52(3), 271-279 (2007)
194. McKiernan E, OBrien K, Grebenchtchikov N et al.: Protein kinase Cd expression in breast cancer as measured by real-time PCR, western blotting and ELISA. Br. J. Cancer 99(10), 1644-1650 (2008)
195. Jackson DN, Foster DA: The enigmatic protein kinase Cd: complex roles in cell proliferation and survival. FASEB J. 18(6), 627-636 (2004)
196. Nabha SM, Glaros S, Hong M et al.: Upregulation of PKC-d contributes to antiestrogen resistance in mammary tumor cells. Oncogene 24(19), 3166-3176 (2005)
197. Shanmugam M, Krett NL, Maizels ET et al.: Regulation of protein kinase C d by estrogen in the MCF-7 human breast cancer cell line. Mol. Cell Endocrinol. 148(1-2), 109-118 (1999)
198. De Servi B, Hermani A, Medunjanin S, Mayer D: Impact of PKCd on estrogen receptor localization and activity in breast cancer cells. Oncogene 24(31), 4946-4955 (2005)
199. Jackson D, Zheng Y, Lyo D et al.: Suppression of cell migration by protein kinase Cd. Oncogene 24(18), 3067-3072 (2005)
200. Shanmugam M, Krett NL, Maizels ET et al.: A role for protein kinase C d in the differential sensitivity of MCF-7 and MDA-MB 231 human breast cancer cells to phorbol ester-induced growth arrest and p21(WAFI/CIP1) induction. Cancer Lett. 172(1), 43-53 (2001)
201. Basu A, Mohanty S, Sun B: Differential sensitivity of breast cancer cells to tumor necrosis factor-a: involvement of protein kinase C. Biochem. Biophys. Res. Commun. 280(3), 883-891 (2001)
202. McCracken MA, Miraglia LJ, McKay RA, Strobl JS: Protein kinase C d is a prosurvival factor in human breast tumor cell lines. Mol. Cancer Ther. 2(3), 273-281 (2003)
203. Yuan P, Xu Y, Ouyang T et al.: [Correlation of BRCA1 and APC aberrant methylation with the response to anthracycline-based neoadjuvant chemotherapy in primary breast cancer]. Zhonghua Zhong Liu Za Zhi 31(4), 282-286 (2009)
204. Seeliger H, Camaj P, Ischenko I et al.: EFEMP1 expression promotes in vivo tumor growth in human pancreatic adenocarcinoma. Mol. Cancer Res. 7(2), 189-198 (2009)
205. Hu B, Thirtamara-Rajamani KK, Sim H, Viapiano MS: Fibulin-3 is uniquely upregulated in malignant gliomas and promotes tumor cell motility and invasion. Mol. Cancer Res. 7(11), 1756-1770 (2009)
206. Albig AR, Neil JR, Schiemann WP: Fibulins 3 and 5 antagonize tumor angiogenesis in vivo. Cancer Res. 66(5), 2621-2629 (2006)
207. Yu Y, Luo R, Lu Z et al.: Biochemistry and biology of ARHI (DIRAS3), an imprinted tumor suppressor gene whose expression is lost in ovarian and breast cancers. Methods Enzymol. 407, 455-468 (2006)
208. Vecchione A, Croce CM, Baldassarre G: Fez1/Lzts1 a new mitotic regulator implicated in cancer development. Cell Div. 2, 24 (2007)
209. van der Weyden L, Adams DJ: The Ras-association domain family (RASSF) members and their role in human tumourigenesis. Biochim. Biophys. Acta 1776(1), 58-85 (2007)
210. Girault I, Tozlu S, Lidereau R, Bieche I: Expression analysis of DNA methyltransferases 1, 3A, and 3B in sporadic breast carcinomas. Clin. Cancer Res. 9(12), 4415-4422 (2003
211. Simon JA, Lange CA: Roles of the EZH2 histone methyltransferase in cancer epigenetics. Mutat. Res. 647(1-2), 21-29 (2008)
212. Cao Q, Yu J, Dhanasekaran SM et al.: Repression of E-cadherin by the polycomb group protein EZH2 in cancer. Oncogene 27(58), 7274-7284 (2008)
213. Dunn L, Demichele A: Genomic predictors of outcome and treatment response in breast cancer. Mol. Diagn. Ther. 13(2), 73-90 (2009)
214. Ross JS, Hatzis C, Symmans WF, Pusztai L, Hortobagyi GN: Commercialized multigene predictors of clinical outcome for breast cancer. Oncologist 13(5), 477-493 (2008)
215. Stadler ZK, Come SE: Review of gene-expression profiling and its clinical use in breast cancer. Crit. Rev. Oncol. Hematol. 69(1), 1-11 (2009)
216. Albain KS, Paik S, vant Veer L: Prediction of adjuvant chemotherapy benefit in endocrine responsive, early breast cancer using multigene assays. Breast 18(Suppl. 3), S141-S145 (2009)
217. Henry NL, Hayes DF: Use of gene-expression profiling to recommend adjuvant chemotherapy for breast cancer. Oncology 21(11), 1301-1309; discussion 1311, 1314, 1319 (2007)
218. Zujewski JA, Kamin L: Trial assessing individualized options for treatment for breast cancer: the TAILORx trial. Future Oncol. 4(5), 603-610 (2008)
219. Duffy MJ, Reilly D, OSullivan C et al.: Urokinase-plasminogen activator, a new and independent prognostic marker in breast cancer. Cancer Res. 50(21), 6827-6829 (1990)
220. Foekens JA, Schmitt M, van Putten WL et al.: Prognostic value of urokinase-type plasminogen activator in 671 primary breast cancer patients. Cancer Res. 52(21), 6101-6105 (1992)
221. Spyratos F, Martin PM, Hacene K et al.: Multiparametric prognostic evaluation of biological factors in primary breast cancer. J. Natl Cancer Inst. 84(16), 1266-1272 (1992)
222. Grondahl-Hansen J, Christensen IJ, Rosenquist C et al.: High levels of urokinase-type plasminogen activator and its inhibitor PAI-1 in cytosolic extracts of breast carcinomas are associated with poor prognosis. Cancer Res. 53(11), 2513-2521 (1993)
223. Janicke F, Schmitt M, Pache L et al.: Urokinase (uPA) and its inhibitor PAI-1 are strong and independent prognostic factors in node-negative breast cancer. Br. Cancer Res. Treat. 24(3), 195-208 (1993)
224. Foekens JA, Schmitt M, van Putten WL et al.: Plasminogen activator inhibitor-1 and prognosis in primary breast cancer. J. Clin. Oncol. 12(8), 1648-1658 (1994)
225. Janicke F, Pache L, Schmitt M et al.: Both the cytosols and detergent extracts of breast cancer tissues are suited to evaluate the prognostic impact of the urokinase-type plasminogen activator and its inhibitor, plasminogen activator inhibitor type 1. Cancer Res. 54(10), 2527-2530 (1994)
226. Foekens JA, Buessecker F, Peters HA et al.: Plasminogen activator inhibitor-2: prognostic relevance in 1012 patients with primary breast cancer. Cancer Res. 55(7), 1423-1427 (1995)
227. Foekens JA, Look MP, Peters HA et al.: Urokinase-type plasminogen activator and its inhibitor PAI-1: predictors of poor response to tamoxifen therapy in recurrent breast cancer. J. Natl Cancer Inst. 87(10), 751-756 (1995)
228. Grondahl-Hansen J, Peters HA, van Putten WL et al.: Prognostic significance of the receptor for urokinase plasminogen activator in breast cancer. Clin. Cancer Res. 1(10), 1079-1087 (1995)
229. Ferno M, Bendahl PO, Borg A et al.: Urokinase plasminogen activator, a strong independent prognostic factor in breast cancer, analysed in steroid receptor cytosols with a luminometric immunoassay. Eur. J. Cancer 32A(5), 793-801 (1996)
230. Grondahl-Hansen J, Christensen IJ, Briand P et al.: Plasminogen activator inhibitor type 1 in cytosolic tumor extracts predicts prognosis in low-risk breast cancer patients. Clin. Cancer Res. 3(2), 233-239 (1997)
231. Schmitt M, Thomssen C, Ulm K et al.: Time-varying prognostic impact of tumour biological factors urokinase (uPA), PAI-1 and steroid hormone receptor status in primary breast cancer. Br. J. Cancer 76(3), 306-311 (1997)
232. Berns EM, Klijn JG, van Putten WL et al.: p53 protein accumulation predicts poor response to tamoxifen therapy of patients with recurrent breast cancer. J. Clin. Oncol. 16(1), 121-127 (1998)
233. Eppenberger U, Kueng W, Schlaeppi JM et al.: Markers of tumor angiogenesis and proteolysis independently define high- and low-risk subsets of node-negative breast cancer patients. J. Clin. Oncol. 16(9), 3129-3136 (1998)
234. Knoop A, Andreasen PA, Andersen JA et al.: Prognostic significance of urokinase-type plasminogen activator and plasminogen activator inhibitor-1 in primary breast cancer. Br. J. Cancer 77(6), 932-940 (1998)
235. Bouchet C, Hacene K, Martin PM et al.: Dissemination risk index based on plasminogen activator system components in primary breast cancer. J. Clin. Oncol. 17(10), 3048-3057 (1999)
236. Meijer-van Gelder ME, Look MP, Bolt-de Vries J et al.: Breast-conserving therapy: proteases as risk factors in relation to survival after local relapse. J. Clin. Oncol. 17(5), 1449-1457 (1999)
237. Foekens JA, Peters HA, Look MP et al.: The urokinase system of plasminogen activation and prognosis in 2780 breast cancer patients. Cancer Res. 60(3), 636-643 (2000)
238. Malmstrom P, Bendahl PO, Boiesen P et al.: S-phase fraction and urokinase plasminogen activator are better markers for distant recurrences than Nottingham Prognostic Index and histologic grade in a prospective study of premenopausal lymph node-negative breast cancer. J. Clin. Oncol. 19(7), 2010-2019 (2001)
239. Harbeck N, Kates RE, Look MP et al.: Enhanced benefit from adjuvant chemotherapy in breast cancer patients classified high-risk according to urokinase-type plasminogen activator (uPA) and plasminogen activator inhibitor type 1 (n = 3424). Cancer Res. 62(16), 4617-4622 (2002)
240. Dorssers LC, Grebenchtchikov N, Brinkman A et al.: The prognostic value of BCAR1 in patients with primary breast cancer. Clin. Cancer Res. 10(18 Pt 1), 6194-6202 (2004)
241. Manders P, Tjan-Heijnen VC, Span PN et al.: Predictive impact of urokinase-type plasminogen activator: plasminogen activator inhibitor type-1 complex on the efficacy of adjuvant systemic therapy in primary breast cancer. Cancer Res. 64(2), 659-664 (2004) (Pubitemid 38120907)
242. Schrohl AS, Holten-Andersen MN, Peters HA et al.: Tumor tissue levels of tissue inhibitor of metalloproteinase-1 as a prognostic marker in primary breast cancer. Clin. Cancer Res. 10(7), 2289-2298 (2004)
243. Borstnar S, Sadikov A, Mozina B, Cufer T: High levels of uPA and PAI-1 predict a good response to anthracyclines. Br. Cancer Res. Treat. 121(3), 615-624 (2010