EGFR associated expression profiles vary with breast tumor subtype

Springer Science and Business Media LLC - Tập 8 Số 1 - Trang 1-19 - 2007
Hoadley, Katherine A1,2,3, Weigman, Victor J2,3,4, Fan, Cheng2,3, Sawyer, Lynda R5, He, Xiaping3, Troester, Melissa A6, Sartor, Carolyn I3,7, Rieger-House, Thais8, Bernard, Philip S8, Carey, Lisa A5, Perou, Charles M1,2,3,9
1Curriculum in Genetics and Molecular Biology, University of North Carolina at Chapel Hill, Chapel Hill, USA
2Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, USA
3Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, USA
4Department of Biology, Program of in Bioinformatics and Computational Biology, University of North Carolina at Chapel Hill, Chapel Hill, USA
5Division of Hematology/Oncology, Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, USA
6Department of Public Health – Biostatistics and Epidemiology Concentration, University of Massachusetts Amherst, Amherst, USA
7Department of Radiation Oncology, University of North Carolina at Chapel Hill, Chapel Hill, USA
8Huntsman Cancer Institute and Department of Pathology, University of Utah School of Medicine, Salt Lake City, USA
9Department of Pathology & Laboratory Medicine, University of North Carolina at Chapel Hill, Chapel Hill, USA

Tóm tắt

The epidermal growth factor receptor (EGFR/HER1) and its downstream signaling events are important for regulating cell growth and behavior in many epithelial tumors types. In breast cancer, the role of EGFR is complex and appears to vary relative to important clinical features including estrogen receptor (ER) status. To investigate EGFR-signaling using a genomics approach, several breast basal-like and luminal epithelial cell lines were examined for sensitivity to EGFR inhibitors. An EGFR-associated gene expression signature was identified in the basal-like SUM102 cell line and was used to classify a diverse set of sporadic breast tumors. In vitro, breast basal-like cell lines were more sensitive to EGFR inhibitors compared to luminal cell lines. The basal-like tumor derived lines were also the most sensitive to carboplatin, which acted synergistically with cetuximab. An EGFR-associated signature was developed in vitro, evaluated on 241 primary breast tumors; three distinct clusters of genes were evident in vivo, two of which were predictive of poor patient outcomes. These EGFR-associated poor prognostic signatures were highly expressed in almost all basal-like tumors and many of the HER2+/ER- and Luminal B tumors. These results suggest that breast basal-like cell lines are sensitive to EGFR inhibitors and carboplatin, and this combination may also be synergistic. In vivo, the EGFR-signatures were of prognostic value, were associated with tumor subtype, and were uniquely associated with the high expression of distinct EGFR-RAS-MEK pathway genes.

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citation_journal_title=Nat Rev Mol Cell Biol; citation_title=Untangling the ErbB signalling network; citation_author=Y Yarden, MX Sliwkowski; citation_volume=2; citation_publication_date=2001; citation_pages=127-137; citation_doi=10.1038/35052073; citation_id=CR1 citation_journal_title=Proc Natl Acad Sci U S A; citation_title=Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications; citation_author=T Sørlie, CM Perou, R Tibshirani, T Aas, S Geisler, H Johnsen, T Hastie, MB Eisen, M van de Rijn, SS Jeffrey, T Thorsen, H Quist, JC Matese, PO Brown, D Botstein, P Eystein Lonning, AL Borresen-Dale; citation_volume=98; citation_publication_date=2001; citation_pages=10869-10874; citation_doi=10.1073/pnas.191367098; citation_id=CR2 citation_journal_title=Proc Natl Acad Sci U S A; citation_title=Repeated observation of breast tumor subtypes in independent gene expression data sets; citation_author=T Sørlie, R Tibshirani, J Parker, T Hastie, JS Marron, A Nobel, S Deng, H Johnsen, R Pesich, S Geisler, J Demeter, CM Perou, PE Lonning, PO Brown, AL Borresen-Dale, D Botstein; citation_volume=100; citation_publication_date=2003; citation_pages=8418-8423; citation_doi=10.1073/pnas.0932692100; citation_id=CR3 citation_journal_title=Nature; citation_title=Molecular portraits of human breast tumours; citation_author=CM Perou, T Sørlie, MB Eisen, M van de Rijn, SS Jeffrey, CA Rees, JR Pollack, DT Ross, H Johnsen, LA Akslen, O Fluge, A Pergamenschikov, C Williams, SX Zhu, PE Lonning, AL Borresen-Dale, PO Brown, D Botstein; citation_volume=406; citation_publication_date=2000; citation_pages=747-752; citation_doi=10.1038/35021093; citation_id=CR4 citation_journal_title=Biotechniques; citation_title=High reproducibility using sodium hydroxide-stripped long oligonucleotide DNA microarrays; citation_author=Z Hu, M Troester, CM Perou; citation_volume=38; citation_publication_date=2005; citation_pages=121-124; citation_doi=10.2144/05381MT02; citation_id=CR5 citation_journal_title=Clin Cancer Res; citation_title=Immunohistochemical and clinical characterization of the basal-like subtype of invasive breast carcinoma; citation_author=TO Nielsen, FD Hsu, K Jensen, M Cheang, G Karaca, Z Hu, T Hernandez-Boussard, C Livasy, D Cowan, L Dressler, LA Akslen, J Ragaz, AM Gown, CB Gilks, M van De Rijn, CM Perou; citation_volume=10; citation_publication_date=2004; citation_pages=5367-3574; citation_doi=10.1158/1078-0432.CCR-04-0220; citation_id=CR6 citation_journal_title=Crit Rev Oncol Hematol; citation_title=Epidermal growth factor-related peptides and their receptors in human malignancies; citation_author=DS Salomon, R Brandt, F Ciardiello, N Normanno; citation_volume=19; citation_publication_date=1995; citation_pages=183-232; citation_doi=10.1016/1040-8428(94)00144-I; citation_id=CR7 citation_journal_title=Int J Radiat Oncol Biol Phys; citation_title=The HER receptor family: a rich target for therapeutic development; citation_author=RD Mass; citation_volume=58; citation_publication_date=2004; citation_pages=932-940; citation_doi=10.1016/j.ijrobp.2003.09.093; citation_id=CR8 citation_journal_title=Oncologist; citation_title=Why the epidermal growth factor receptor? The rationale for cancer therapy; citation_author=J Baselga; citation_volume=7 Suppl 4; citation_publication_date=2002; citation_pages=2-8; citation_doi=10.1634/theoncologist.7-suppl_4-2; citation_id=CR9 citation_journal_title=Drugs; citation_title=Gefitinib; citation_author=CR Culy, D Faulds; citation_volume=62; citation_publication_date=2002; citation_pages=2237-48; discussion 2249-50; citation_doi=10.2165/00003495-200262150-00008; citation_id=CR10 citation_journal_title=Nat Rev Drug Discov; citation_title=Cetuximab; citation_author=J Graham, M Muhsin, P Kirkpatrick; citation_volume=3; citation_publication_date=2004; citation_pages=549-550; citation_doi=10.1038/nrd1287; citation_id=CR11 citation_journal_title=Nat Rev Drug Discov; citation_title=Erlotinib hydrochloride; citation_author=J Dowell, JD Minna, P Kirkpatrick; citation_volume=4; citation_publication_date=2005; citation_pages=13-14; citation_doi=10.1038/nrd1612; citation_id=CR12 citation_journal_title=Int J Clin Oncol; citation_title=Molecular target-based cancer therapy: tyrosine kinase inhibitors; citation_author=K Tamura, M Fukuoka; citation_volume=8; citation_publication_date=2003; citation_pages=207-211; citation_doi=10.1007/s10147-003-0320-1; citation_id=CR13 citation_journal_title=Clin Cancer Res; citation_title=Antitumor effect and potentiation of cytotoxic drugs activity in human cancer cells by ZD-1839 (Iressa), an epidermal growth factor receptor-selective tyrosine kinase inhibitor; citation_author=F Ciardiello, R Caputo, R Bianco, V Damiano, G Pomatico, S De Placido, AR Bianco, G Tortora; citation_volume=6; citation_publication_date=2000; citation_pages=2053-2063; citation_id=CR14 citation_journal_title=Clin Cancer Res; citation_title=Resistance to gefitinib in PTEN-null HER-overexpressing tumor cells can be overcome through restoration of PTEN function or pharmacologic modulation of constitutive phosphatidylinositol 3'-kinase/Akt pathway signaling; citation_author=QB She, D Solit, A Basso, MM Moasser; citation_volume=9; citation_publication_date=2003; citation_pages=4340-4346; citation_id=CR15 citation_journal_title=Cancer Res; citation_title=The tyrosine kinase inhibitor ZD1839 ("Iressa") inhibits HER2-driven signaling and suppresses the growth of HER2-overexpressing tumor cells; citation_author=MM Moasser, A Basso, SD Averbuch, N Rosen; citation_volume=61; citation_publication_date=2001; citation_pages=7184-7188; citation_id=CR16 citation_journal_title=Oncogene; citation_title=Loss of PTEN/MMAC1/TEP in EGF receptor-expressing tumor cells counteracts the antitumor action of EGFR tyrosine kinase inhibitors; citation_author=R Bianco, I Shin, CA Ritter, FM Yakes, A Basso, N Rosen, J Tsurutani, PA Dennis, GB Mills, CL Arteaga; citation_volume=22; citation_publication_date=2003; citation_pages=2812-2822; citation_doi=10.1038/sj.onc.1206388; citation_id=CR17 citation_journal_title=Br J Cancer; citation_title=Dual blockade of EGFR and ERK1/2 phosphorylation potentiates growth inhibition of breast cancer cells; citation_author=DC Lev, LS Kim, V Melnikova, M Ruiz, HN Ananthaswamy, JE Price; citation_volume=91; citation_publication_date=2004; citation_pages=795-802; citation_id=CR18 citation_journal_title=J Cell Physiol; citation_title=The MEK/MAPK pathway is involved in the resistance of breast cancer cells to the EGFR tyrosine kinase inhibitor gefitinib; citation_author=N Normanno, A De Luca, MR Maiello, M Campiglio, M Napolitano, M Mancino, A Carotenuto, G Viglietto, S Menard; citation_volume=207; citation_publication_date=2006; citation_pages=420-427; citation_doi=10.1002/jcp.20588; citation_id=CR19 citation_journal_title=Int J Cancer; citation_title=Enhanced cytotoxicity induced by gefitinib and specific inhibitors of the Ras or phosphatidyl inositol-3 kinase pathways in non-small cell lung cancer cells; citation_author=ML Janmaat, JA Rodriguez, M Gallegos-Ruiz, FA Kruyt, G Giaccone; citation_volume=118; citation_publication_date=2006; citation_pages=209-214; citation_doi=10.1002/ijc.21290; citation_id=CR20 citation_journal_title=J Clin Invest; citation_title=AlphaB-crystallin is a novel oncoprotein that predicts poor clinical outcome in breast cancer; citation_author=JV Moyano, JR Evans, F Chen, M Lu, ME Werner, F Yehiely, LK Diaz, D Turbin, G Karaca, E Wiley, TO Nielsen, CM Perou, VL Cryns; citation_volume=116; citation_publication_date=2006; citation_pages=261-270; citation_doi=10.1172/JCI25888; citation_id=CR21 citation_journal_title=Cancer Res; citation_title=Cell-Type-Specific Responses to Chemotherapeutics in Breast Cancer; citation_author=MA Troester, KA Hoadley, T Sorlie, BS Herbert, AL Borresen-Dale, PE Lonning, JW Shay, WK Kaufmann, CM Perou; citation_volume=64; citation_publication_date=2004; citation_pages=4218-4226; citation_doi=10.1158/0008-5472.CAN-04-0107; citation_id=CR22 citation_journal_title=Environ Health Perspect; citation_title=Prediction of toxicant-specific gene expression signatures after chemotherapeutic treatment of breast cell lines; citation_author=MA Troester, KA Hoadley, JS Parker, CM Perou; citation_volume=112; citation_publication_date=2004; citation_pages=1607-1613; citation_doi=10.1289/ehp.7204; citation_id=CR23 citation_journal_title=Cancer Res; citation_title=Role of epidermal growth factor receptor and STAT-3 activation in autonomous proliferation of SUM-102PT human breast cancer cells; citation_author=CI Sartor, ML Dziubinski, CL Yu, R Jove, SP Ethier; citation_volume=57; citation_publication_date=1997; citation_pages=978-987; citation_id=CR24 citation_journal_title=Cancer Res; citation_title=Gene expression profiling identifies molecular subtypes of inflammatory breast cancer; citation_author=F Bertucci, P Finetti, J Rougemont, E Charafe-Jauffret, N Cervera, C Tarpin, C Nguyen, L Xerri, R Houlgatte, J Jacquemier, P Viens, D Birnbaum; citation_volume=65; citation_publication_date=2005; citation_pages=2170-2178; citation_doi=10.1158/0008-5472.CAN-04-4115; citation_id=CR25 citation_journal_title=Adv Enzyme Regul; citation_title=Quantitative analysis of dose-effect relationships: the combined effects of multiple drugs or enzyme inhibitors; citation_author=TC Chou, P Talalay; citation_volume=22; citation_publication_date=1984; citation_pages=27-55; citation_doi=10.1016/0065-2571(84)90007-4; citation_id=CR26 citation_journal_title=J Pathol; citation_title=Cyclin E overexpression and amplification in human tumours; citation_author=P Schraml, C Bucher, H Bissig, A Nocito, P Haas, K Wilber, S Seelig, J Kononen, MJ Mihatsch, S Dirnhofer, G Sauter; citation_volume=200; citation_publication_date=2003; citation_pages=375-382; citation_doi=10.1002/path.1356; citation_id=CR27 citation_journal_title=Clin Cancer Res; citation_title=Which cyclin E prevails as prognostic marker for breast cancer? Results from a retrospective study involving 635 lymph node-negative breast cancer patients; citation_author=AM Sieuwerts, MP Look, ME Meijer-van Gelder, M Timmermans, AM Trapman, RR Garcia, M Arnold, AJ Goedheer, V de Weerd, H Portengen, JG Klijn, JA Foekens; citation_volume=12; citation_publication_date=2006; citation_pages=3319-3328; citation_doi=10.1158/1078-0432.CCR-06-0225; citation_id=CR28 citation_journal_title=Cancer Res; citation_title=The prognostic implication of the basal-like (cyclin E high/p27 low/p53+/glomeruloid-microvascular-proliferation+) phenotype of BRCA1-related breast cancer; citation_author=WD Foulkes, JS Brunet, IM Stefansson, O Straume, PO Chappuis, LR Begin, N Hamel, JR Goffin, N Wong, M Trudel, L Kapusta, P Porter, LA Akslen; citation_volume=64; citation_publication_date=2004; citation_pages=830-835; citation_doi=10.1158/0008-5472.CAN-03-2970; citation_id=CR29 citation_journal_title=Int J Oncol; citation_title=EGFR family signaling and its association with breast cancer development and resistance to chemotherapy (Review); citation_author=PM Navolanic, LS Steelman, JA McCubrey; citation_volume=22; citation_publication_date=2003; citation_pages=237-252; citation_id=CR30 citation_journal_title=Nature; citation_title=AFX-like Forkhead transcription factors mediate cell-cycle regulation by Ras and PKB through p27kip1; citation_author=RH Medema, GJ Kops, JL Bos, BM Burgering; citation_volume=404; citation_publication_date=2000; citation_pages=782-787; citation_doi=10.1038/35008115; citation_id=CR31 citation_journal_title=J Biol Chem; citation_title=The p42/p44 mitogen-activated protein kinase activation triggers p27Kip1 degradation independently of CDK2/cyclin E in NIH 3T3 cells; citation_author=C Delmas, S Manenti, A Boudjelal, C Peyssonnaux, A Eychene, JM Darbon; citation_volume=276; citation_publication_date=2001; citation_pages=34958-34965; citation_doi=10.1074/jbc.M101714200; citation_id=CR32 citation_journal_title=N Engl J Med; citation_title=A gene-expression signature as a predictor of survival in breast cancer; citation_author=MJ van de Vijver, YD He, LJ van't Veer, H Dai, AA Hart, DW Voskuil, GJ Schreiber, JL Peterse, C Roberts, MJ Marton, M Parrish, D Atsma, A Witteveen, A Glas, L Delahaye, T van der Velde, H Bartelink, S Rodenhuis, ET Rutgers, SH Friend, R Bernards; citation_volume=347; citation_publication_date=2002; citation_pages=1999-2009; citation_doi=10.1056/NEJMoa021967; citation_id=CR33 citation_journal_title=Proc Natl Acad Sci U S A; citation_title=Robustness, scalability, and integration of a wound-response gene expression signature in predicting breast cancer survival; citation_author=HY Chang, DS Nuyten, JB Sneddon, T Hastie, R Tibshirani, T Sorlie, H Dai, YD He, LJ van't Veer, H Bartelink, M van de Rijn, PO Brown, MJ van de Vijver; citation_volume=102; citation_publication_date=2005; citation_pages=3738-3743; citation_doi=10.1073/pnas.0409462102; citation_id=CR34 citation_journal_title=Genome Biol; citation_title=Identification of conserved gene expression features between murine mammary carcinoma models and human breast tumors; citation_author=JI Herschkowitz, K Simin, VJ Weigman, I Mikaelian, J Usary, Z Hu, KE Rasmussen, LP Jones, S Assefnia, S Chandrasekharan, MG Backlund, Y Yin, AI Khramtsov, R Bastein, J Quackenbush, RI Glazer, PH Brown, JE Green, L Kopelovich, PA Furth, JP Palazzo, OI Olopade, PS Bernard, GA Churchill, T Van Dyke, CM Perou; citation_volume=8; citation_publication_date=2007; citation_pages=R76; citation_doi=10.1186/gb-2007-8-5-r76; citation_id=CR35 citation_journal_title=Front Biosci; citation_title=Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors in breast cancer: current status and future development; citation_author=N Normanno, A De Luca, MR Maiello, M Mancino, A D'Antonio, M Macaluso, F Caponigro, A Giordano; citation_volume=10; citation_publication_date=2005; citation_pages=2611-2617; citation_doi=10.2741/1725; citation_id=CR36 citation_journal_title=Endocr Relat Cancer; citation_title=Overview of tyrosine kinase inhibitors in clinical breast cancer; citation_author=A Agrawal, E Gutteridge, JM Gee, RI Nicholson, JF Robertson; citation_volume=12 Suppl 1; citation_publication_date=2005; citation_pages=S135-44; citation_doi=10.1677/erc.1.01059; citation_id=CR37 citation_journal_title=Cell Signal; citation_title=Autocrine, paracrine and juxtacrine signaling by EGFR ligands; citation_author=AB Singh, RC Harris; citation_volume=17; citation_publication_date=2005; citation_pages=1183-1193; citation_doi=10.1016/j.cellsig.2005.03.026; citation_id=CR38 citation_journal_title=Clin Cancer Res; citation_title=Placental cadherin and the basal epithelial phenotype of BRCA1-related breast cancer; citation_author=JB Arnes, JS Brunet, I Stefansson, LR Begin, N Wong, PO Chappuis, LA Akslen, WD Foulkes; citation_volume=11; citation_publication_date=2005; citation_pages=4003-4011; citation_doi=10.1158/1078-0432.CCR-04-2064; citation_id=CR39 citation_journal_title=J Natl Cancer Inst; citation_title=Germline BRCA1 mutations and a basal epithelial phenotype in breast cancer; citation_author=WD Foulkes, IM Stefansson, PO Chappuis, LR Begin, JR Goffin, N Wong, M Trudel, LA Akslen; citation_volume=95; citation_publication_date=2003; citation_pages=1482-1485; citation_doi=10.1093/jnci/djg050; citation_id=CR40 citation_journal_title=Cancer Res; citation_title=BRCA1 mutation analysis of 41 human breast cancer cell lines reveals three new deleterious mutants; citation_author=F Elstrodt, A Hollestelle, JH Nagel, M Gorin, M Wasielewski, A van den Ouweland, SD Merajver, SP Ethier, M Schutte; citation_volume=66; citation_publication_date=2006; citation_pages=41-45; citation_doi=10.1158/0008-5472.CAN-05-2853; citation_id=CR41 citation_journal_title=Biochem Biophys Res Commun; citation_title=The carboxyl-terminal of BRCA1 is required for subnuclear assembly of RAD51 after treatment with cisplatin but not ionizing radiation in human breast and ovarian cancer cells; citation_author=C Zhou, P Huang, J Liu; citation_volume=336; citation_publication_date=2005; citation_pages=952-960; citation_doi=10.1016/j.bbrc.2005.08.197; citation_id=CR42 citation_journal_title=J Biol Chem; citation_title=The breast cancer susceptibility gene BRCA1 is required for subnuclear assembly of Rad51 and survival following treatment with the DNA cross-linking agent cisplatin; citation_author=A Bhattacharyya, US Ear, BH Koller, RR Weichselbaum, DK Bishop; citation_volume=275; citation_publication_date=2000; citation_pages=23899-23903; citation_doi=10.1074/jbc.C000276200; citation_id=CR43 citation_journal_title=Cancer Res; citation_title=BRCA1 up-regulation is associated with repair-mediated resistance to cis-diamminedichloroplatinum(II); citation_author=A Husain, G He, ES Venkatraman, DR Spriggs; citation_volume=58; citation_publication_date=1998; citation_pages=1120-1123; citation_id=CR44 citation_journal_title=Br J Cancer; citation_title=BRCA1 expression modulates chemosensitivity of BRCA1-defective HCC1937 human breast cancer cells; citation_author=P Tassone, P Tagliaferri, A Perricelli, S Blotta, B Quaresima, ML Martelli, A Goel, V Barbieri, F Costanzo, CR Boland, S Venuta; citation_volume=88; citation_publication_date=2003; citation_pages=1285-1291; citation_doi=10.1038/sj.bjc.6600859; citation_id=CR45 citation_journal_title=Cancer Res; citation_title=BRCA1 functions as a differential modulator of chemotherapy-induced apoptosis; citation_author=JE Quinn, RD Kennedy, PB Mullan, PM Gilmore, M Carty, PG Johnston, DP Harkin; citation_volume=63; citation_publication_date=2003; citation_pages=6221-6228; citation_id=CR46 citation_journal_title=J Natl Cancer Inst; citation_title=The role of BRCA1 in the cellular response to chemotherapy; citation_author=RD Kennedy, JE Quinn, PB Mullan, PG Johnston, DP Harkin; citation_volume=96; citation_publication_date=2004; citation_pages=1659-1668; citation_doi=10.1093/jnci/djh312; citation_id=CR47 citation_journal_title=Ann Oncol; citation_title=Sequence-dependent antiproliferative effects of cytotoxic drugs and epidermal growth factor receptor inhibitors; citation_author=MP Morelli, T Cascone, T Troiani, F De Vita, M Orditura, G Laus, SG Eckhardt, S Pepe, G Tortora, F Ciardiello; citation_volume=16 Suppl 4; citation_publication_date=2005; citation_pages=iv61-iv68; citation_id=CR48 citation_journal_title=Anticancer Res; citation_title=Reduction of cisplatin dosage by ZD 1839; citation_author=M Hambek, M Baghi, K Strebhardt, H Baumann, W Gstottner, R Knecht; citation_volume=25; citation_publication_date=2005; citation_pages=3985-3988; citation_id=CR49 Cetuximab Alone and Cetuximab With Carboplatin in ER/PR-Negative, HER-2 Nonoverexpressing Metastatic Breast Cancer. [ http://www.clinicaltrials.gov/ct/show/NCT00232505 ] Cytoscape. [ http://www.cytoscape.org ] citation_journal_title=Genome Res; citation_title=Cytoscape: A Software Environment for Integrated Models of Biomolecular Interaction Networks; citation_author=P Shannon, A Markiel, O Ozier, NS Baliga, JT Wang, D Ramage, N Amin, B Schwikowski, T Ideker; citation_volume=13; citation_publication_date=2003; citation_pages=2498-2504; citation_doi=10.1101/gr.1239303; citation_id=CR52 citation_journal_title=J Clin Oncol; citation_title=Molecular changes in tamoxifen-resistant breast cancer: relationship between estrogen receptor, HER-2, and p38 mitogen-activated protein kinase; citation_author=MC Gutierrez, S Detre, S Johnston, SK Mohsin, J Shou, DC Allred, R Schiff, CK Osborne, M Dowsett; citation_volume=23; citation_publication_date=2005; citation_pages=2469-2476; citation_doi=10.1200/JCO.2005.01.172; citation_id=CR53 citation_journal_title=Clin Cancer Res; citation_title=HER-2 amplification, HER-1 expression, and tamoxifen response in estrogen receptor-positive metastatic breast cancer: a southwest oncology group study; citation_author=G Arpino, SJ Green, DC Allred, D Lew, S Martino, CK Osborne, RM Elledge; citation_volume=10; citation_publication_date=2004; citation_pages=5670-5676; citation_doi=10.1158/1078-0432.CCR-04-0110; citation_id=CR54 citation_journal_title=Breast Cancer Res Treat; citation_title=Bidirectional cross talk between ERalpha and EGFR signalling pathways regulates tamoxifen-resistant growth; citation_author=DJ Britton, IR Hutcheson, JM Knowlden, D Barrow, M Giles, RA McClelland, JM Gee, RI Nicholson; citation_volume=96; citation_publication_date=2006; citation_pages=131-146; citation_doi=10.1007/s10549-005-9070-2; citation_id=CR55 citation_journal_title=J Clin Oncol; citation_title=Estrogen-independent proliferation is present in estrogen-receptor HER2-positive primary breast cancer after neoadjuvant letrozole; citation_author=MJ Ellis, Y Tao, O Young, S White, AD Proia, J Murray, L Renshaw, D Faratian, J Thomas, M Dowsett, A Krause, DB Evans, WR Miller, JM Dixon; citation_volume=24; citation_publication_date=2006; citation_pages=3019-3025; citation_doi=10.1200/JCO.2005.04.3034; citation_id=CR56 citation_journal_title=Ann Oncol; citation_title=Benefit from adjuvant tamoxifen therapy in primary breast cancer patients according oestrogen receptor, progesterone receptor, EGF receptor and HER2 status; citation_author=M Dowsett, J Houghton, C Iden, J Salter, J Farndon, R A'Hern, R Sainsbury, M Baum; citation_volume=17; citation_publication_date=2006; citation_pages=818-826; citation_doi=10.1093/annonc/mdl016; citation_id=CR57 citation_journal_title=J Natl Cancer Inst; citation_title=Mechanisms of tamoxifen resistance: increased estrogen receptor-HER2/neu cross-talk in ER/HER2-positive breast cancer; citation_author=J Shou, S Massarweh, CK Osborne, AE Wakeling, S Ali, H Weiss, R Schiff; citation_volume=96; citation_publication_date=2004; citation_pages=926-935; citation_doi=10.1093/jnci/djh166; citation_id=CR58 citation_journal_title=Br J Cancer; citation_title=Phase II study of gefitinib in combination with docetaxel as first-line therapy in metastatic breast cancer; citation_author=F Ciardiello, T Troiani, F Caputo, M De Laurentiis, G Tortora, G Palmieri, F De Vita, MR Diadema, M Orditura, G Colantuoni, C Gridelli, G Catalano, S De Placido, AR Bianco; citation_volume=94; citation_publication_date=2006; citation_pages=1604-1609; citation_id=CR59 citation_journal_title=Lancet Oncol; citation_title=Preoperative gefitinib versus gefitinib and anastrozole in postmenopausal patients with oestrogen-receptor positive and epidermal-growth-factor-receptor-positive primary breast cancer: a double-blind placebo-controlled phase II randomised trial; citation_author=A Polychronis, HD Sinnett, D Hadjiminas, H Singhal, JL Mansi, D Shivapatham, S Shousha, J Jiang, D Peston, N Barrett, D Vigushin, K Morrison, E Beresford, S Ali, MJ Slade, RC Coombes; citation_volume=6; citation_publication_date=2005; citation_pages=383-391; citation_doi=10.1016/S1470-2045(05)70176-5; citation_id=CR60 citation_journal_title=Int J Cancer; citation_title=Akt is frequently activated in HER2/neu-positive breast cancers and associated with poor prognosis among hormone-treated patients; citation_author=E Tokunaga, Y Kimura, E Oki, N Ueda, M Futatsugi, K Mashino, M Yamamoto, M Ikebe, Y Kakeji, H Baba, Y Maehara; citation_volume=118; citation_publication_date=2006; citation_pages=284-289; citation_doi=10.1002/ijc.21358; citation_id=CR61 citation_journal_title=Clin Cancer Res; citation_title=Activation of the Akt/mammalian target of rapamycin/4E-BP1 pathway by ErbB2 overexpression predicts tumor progression in breast cancers; citation_author=X Zhou, M Tan, V Stone Hawthorne, KS Klos, KH Lan, Y Yang, W Yang, TL Smith, D Shi, D Yu; citation_volume=10; citation_publication_date=2004; citation_pages=6779-6788; citation_doi=10.1158/1078-0432.CCR-04-0112; citation_id=CR62 citation_journal_title=J Biol Chem; citation_title=The small heat shock protein alpha B-crystallin negatively regulates cytochrome c- and caspase-8-dependent activation of caspase-3 by inhibiting its autoproteolytic maturation; citation_author=MC Kamradt, F Chen, VL Cryns; citation_volume=276; citation_publication_date=2001; citation_pages=16059-16063; citation_doi=10.1074/jbc.C100107200; citation_id=CR63 citation_journal_title=J Biol Chem; citation_title=The small heat shock protein alpha B-crystallin is a novel inhibitor of TRAIL-induced apoptosis that suppresses the activation of caspase-3; citation_author=MC Kamradt, M Lu, ME Werner, T Kwan, F Chen, A Strohecker, S Oshita, JC Wilkinson, C Yu, PG Oliver, CS Duckett, DJ Buchsbaum, AF LoBuglio, VC Jordan, VL Cryns; citation_volume=280; citation_publication_date=2005; citation_pages=11059-11066; citation_doi=10.1074/jbc.M413382200; citation_id=CR64 citation_journal_title=Oncogene; citation_title=Haploid loss of Ki-ras delays mammary tumor progression in C3 (1)/SV40 Tag transgenic mice; citation_author=ML Liu, MA Shibata, FC Von Lintig, W Wang, S Cassenaer, GR Boss, JE Green; citation_volume=20; citation_publication_date=2001; citation_pages=2044-2049; citation_doi=10.1038/sj.onc.1204280; citation_id=CR65 citation_journal_title=Breast Cancer Res Treat; citation_title=A multicentre phase II study on gefitinib in taxane- and anthracycline-pretreated metastatic breast cancer; citation_author=G von Minckwitz, W Jonat, P Fasching, A du Bois, U Kleeberg, HJ Luck, E Kettner, J Hilfrich, W Eiermann, J Torode, A Schneeweiss; citation_volume=89; citation_publication_date=2005; citation_pages=165-172; citation_doi=10.1007/s10549-004-1720-2; citation_id=CR66 citation_journal_title=Ann Oncol; citation_title=Gefitinib (ZD1839) combined with weekly epirubicin in patients with metastatic breast cancer: a phase I study with biological correlate; citation_author=G Gasparini, R Sarmiento, S Amici, R Longo, D Gattuso, M Zancan, M Gion; citation_volume=16; citation_publication_date=2005; citation_pages=1867-1873; citation_doi=10.1093/annonc/mdi393; citation_id=CR67 citation_journal_title=Breast Cancer Res Treat; citation_title=Paclitaxel and carboplatin as first-line chemotherapy combined with gefitinib (IRESSA) in patients with advanced breast cancer: a phase I/II study conducted by the Hellenic Cooperative Oncology Group; citation_author=G Fountzilas, D Pectasides, A Kalogera-Fountzila, D Skarlos, HP Kalofonos, C Papadimitriou, D Bafaloukos, S Lambropoulos, S Papadopoulos, H Kourea, C Markopoulos, H Linardou, D Mavroudis, E Briasoulis, N Pavlidis, E Razis, P Kosmidis, H Gogas; citation_volume=92; citation_publication_date=2005; citation_pages=1-9; citation_doi=10.1007/s10549-005-0322-y; citation_id=CR68 Asterand: Human breast cancer cell lines. [ http://www.asterand.com/Asterand/BIOREPOSITORY/hbreastcancercelllines.aspx ] Tissue Culture Facility at the University of North Carolina at Chapel Hill. [ http://www.unc.edu/depts/tcf/info.html ] citation_journal_title=BMC Genomics; citation_title=The molecular portraits of breast tumors are conserved across microarray platforms; citation_author=Z Hu, C Fan, DS Oh, JS Marron, X He, BF Qaqish, C Livasy, LA Carey, E Reynolds, L Dressler, A Nobel, J Parker, MG Ewend, LR Sawyer, J Wu, Y Liu, R Nanda, M Tretiakova, A Ruiz Orrico, D Dreher, JP Palazzo, L Perreard, E Nelson, M Mone, H Hansen, M Mullins, JF Quackenbush, MJ Ellis, OI Olopade, PS Bernard, CM Perou; citation_volume=7; citation_publication_date=2006; citation_pages=96; citation_doi=10.1186/1471-2164-7-96; citation_id=CR71 citation_journal_title=J Clin Oncol; citation_title=Estrogen-regulated genes predict survival in hormone receptor-positive breast cancers; citation_author=DS Oh, MA Troester, J Usary, Z Hu, X He, C Fan, J Wu, LA Carey, CM Perou; citation_volume=24; citation_publication_date=2006; citation_pages=1656-1664; citation_doi=10.1200/JCO.2005.03.2755; citation_id=CR72 citation_journal_title=Cancer Res; citation_title=Molecular portraits and 70-gene prognosis signature are preserved throughout the metastatic process of breast cancer; citation_author=B Weigelt, Z Hu, X He, C Livasy, LA Carey, MG Ewend, AM Glas, CM Perou, LJ Van't Veer; citation_volume=65; citation_publication_date=2005; citation_pages=9155-9158; citation_doi=10.1158/0008-5472.CAN-05-2553; citation_id=CR73 citation_journal_title=Breast Cancer Res; citation_title=Classification and risk stratification of invasive breast carcinomas using a real-time quantitative RT-PCR assay; citation_author=L Perreard, C Fan, JF Quackenbush, M Mullins, NP Gauthier, E Nelson, M Mone, H Hansen, SS Buys, K Rasmussen, AR Orrico, D Dreher, R Walters, J Parker, Z Hu, X He, JP Palazzo, OI Olopade, A Szabo, CM Perou, PS Bernard; citation_volume=8; citation_publication_date=2006; citation_pages=R23; citation_doi=10.1186/bcr1399; citation_id=CR74 UNC Microarray Database. [ https://genome.unc.edu/cgi-bin/SMD/publication/viewPublication.pl?pub_no=62 ] citation_journal_title=Proc Natl Acad Sci U S A; citation_title=Cluster analysis and display of genome-wide expression patterns; citation_author=MB Eisen, PT Spellman, PO Brown, D Botstein; citation_volume=95; citation_publication_date=1998; citation_pages=14863-14868; citation_doi=10.1073/pnas.95.25.14863; citation_id=CR76 citation_journal_title=Methods Enzymol; citation_title=DNA arrays for analysis of gene expression; citation_author=MB Eisen, PO Brown; citation_volume=303; citation_publication_date=1999; citation_pages=179-205; citation_doi=10.1016/S0076-6879(99)03014-1; citation_id=CR77 citation_journal_title=Proc Natl Acad Sci U S A; citation_title=Significance analysis of microarrays applied to the ionizing radiation response.; citation_author=V Tusher, R Tibshirani, G Chu; citation_volume=98; citation_publication_date=2001; citation_pages=5116-5121; citation_doi=10.1073/pnas.091062498; citation_id=CR78 citation_journal_title=Genome Biol; citation_title=Identifying biological themes within lists of genes with EASE; citation_author=DA Hosack, G Dennis, BT Sherman, HC Lane, RA Lempicki; citation_volume=4; citation_publication_date=2003; citation_pages=R70; citation_doi=10.1186/gb-2003-4-10-r70; citation_id=CR79 KEGG: Kyoto Encyclopedia of Genes and Genomes. [ http://www.genome.ad.jp/kegg/ ] citation_journal_title=Nucleic Acids Res; citation_title=KEGG: Kyoto Encyclopedia of Genes and Genomes; citation_author=H Ogata, S Goto, K Sato, W Fujibuchi, H Bono, M Kanehisa; citation_volume=27; citation_publication_date=1999; citation_pages=29-34; citation_doi=10.1093/nar/27.1.29; citation_id=CR81 BioCarta. [ http://www.biocarta.com ] citation_journal_title=N Engl J Med; citation_title=Concordance among gene-expression-based predictors for breast cancer; citation_author=C Fan, DS Oh, L Wessels, B Weigelt, DS Nuyten, AB Nobel, LJ van't Veer, CM Perou; citation_volume=355; citation_publication_date=2006; citation_pages=560-569; citation_doi=10.1056/NEJMoa052933; citation_id=CR83