Functional relationship and gene ontology classification of breast cancer biomarkers.

Breast cancer is a complex disease that still imposes a significant healthcare burden on women worldwide. The etiology of breast cancer is not known but significant advances have been made in the area of early detection and treatment. The advent of advanced molecular biology techniques, mapping of the human genome and availability of high throughput genomic and proteomic strategies opens up new opportunities and will potentially lead to the discovery of novel biomarkers for early detection and prognostication of breast cancer. Currently, many biomarkers, particularly the hormonal and epidermal growth factor receptors, are being utilized for breast cancer prognosis. Unfortunately, none of the biomarkers in use have sufficient diagnostic, prognostic and/or predictive power across all categories and stages of breast cancer. It is recognized that more useful information can be generated if tumors are interrogated with multiple markers. But choosing the right combination of biomarkers is challenging, because 1) multiple pathways are involved, 2) up to 62 genes and their protein products are potentially involved in breast cancer-related mechanisms and 3) the more markers evaluated, the more the time and cost involved. This review summarizes the current literature on selected biomarkers for breast cancer, discusses the functional relationships, and groups the selected genes based on a Gene Ontology classification.

[1]  K. Ulm,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. , 1994, Cancer research.

[2]  P. V. van Diest,et al.  Cyclin D1 expression in invasive breast cancer. Correlations and prognostic value. , 1997, The American journal of pathology.

[3]  J. Roca,et al.  DNA transport by a type II DNA topoisomerase: Evidence in favor of a two-gate mechanism , 1994, Cell.

[4]  S. Chevillard,et al.  Ki67 index and S-phase fraction in human breast carcinomas. Comparison and correlations with prognostic factors. , 1990, American journal of clinical pathology.

[5]  K. Kunishio,et al.  Incidence of Mutation and Deletion in Topoisomerase IIα mRNA of Etoposide and mAMSA–resistant Cell Lines , 2001, Japanese journal of cancer research : Gann.

[6]  L. Devy,et al.  MT1‐MMP expression promotes tumor growth and angiogenesis through an up‐regulation of vascular endothelial growth factor expression , 2002, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[7]  S. Seal,et al.  Localization of a breast cancer susceptibility gene, BRCA2, to chromosome 13q12-13. , 1994, Science.

[8]  M. Piccart-Gebhart.  Herceptin®: the future in adjuvant breast cancer therapy , 2001, Anti-cancer drugs.

[9]  E. Milgrom,et al.  Oestrogen receptor negative-progesterone receptor positive phenotype in 1,211 breast tumours. , 1992, British Journal of Cancer.

[10]  A. Kossakowska,et al.  Comparative analysis of the expression patterns of metalloproteinases and their inhibitors in breast neoplasia, sporadic colorectal neoplasia, pulmonary carcinomas and malignant non-Hodgkin's lymphomas in humans. , 1996, British Journal of Cancer.

[11]  J. Bergh,et al.  Use of TPS and CA 15-3 assays for monitoring chemotherapy in metastatic breast cancer patients. , 2000, Anticancer research.

[12]  J. Holden,et al.  Human DNA topoisomerase II-alpha: a new marker of cell proliferation in invasive breast cancer. , 1997, Human pathology.

[13]  H. Kreipe,et al.  Proliferation-associated nuclear antigen Ki-S1 is identical with topoisomerase II alpha. Delineation of a carboxy-terminal epitope with peptide antibodies. , 1995, The American journal of pathology.

[14]  I. Giannopoulou,et al.  Correlation of Tissue Inhibitor of Metalloproteinase-2 with Proliferative Activity and Patients’ Survival in Breast Cancer , 2002, Modern Pathology.

[15]  M. Loda,et al.  The cell cycle inhibitor p27 is an independent prognostic marker in small (T1a,b) invasive breast carcinomas. , 1997, Cancer research.

[16]  L. Liotta,et al.  Metastatic potential correlates with enzymatic degradation of basement membrane collagen , 1980, Nature.

[17]  Yudong D. He,et al.  Gene expression profiling predicts clinical outcome of breast cancer , 2002, Nature.

[18]  G. Gasparini,et al.  Prognostic value of vascular endothelial growth factor in breast cancer. , 2000, The oncologist.

[19]  C. Clavel,et al.  Detection and localization of mRNAs encoding matrix metalloproteinases and their tissue inhibitor in human breast pathology. , 1993, Invasion & metastasis.

[20]  K. Kinzler,et al.  14-3-3σ Is a p53-Regulated Inhibitor of G2/M Progression , 1997 .

[21]  K. Hillan,et al.  Importance of VEGF for breast cancer angiogenesis in vivo: implications from intravital microscopy of combination treatments with an anti-VEGF neutralizing monoclonal antibody and doxorubicin. , 1999, Anticancer research.

[22]  A. Dnistrian,et al.  CA 15-3 and carcinoembryonic antigen in the clinical evaluation of breast cancer. , 1991, Clinica chimica acta; international journal of clinical chemistry.

[23]  Á. Ruibal,et al.  Circulating CA 15-3 levels in the postsurgical follow-up of breast cancer patients and in non-malignant diseases , 1989, Breast Cancer Research and Treatment.

[24]  S. Dacic,et al.  Immunohistochemical Profile of Cystosarcoma Phyllodes of the Breast: A Study of 23 Cases , 2002, The breast journal.

[25]  J. Foekens,et al.  Plasminogen activator inhibitor-2: prognostic relevance in 1012 patients with primary breast cancer. , 1995, Cancer research.

[26]  G. Stamp,et al.  Mice lacking cyclin D1 are small and show defects in eye and mammary gland development. , 1995, Genes & development.

[27]  L. Liotta,et al.  Immunohistochemical distribution of type IV collagenase in normal, benign, and malignant breast tissue. , 1990, The American journal of pathology.

[28]  R. Sutherland,et al.  Cyclin-dependent kinases as downstream targets of oestrogen action: potential prognostic indicators and therapeutic targets , 1997 .

[29]  M. Cenci,et al.  Cytological analysis and immunocytochemical expression of Ki67 and Bcl-2 in breast proliferative lesions. , 2002, Anticancer research.

[30]  G M Clark,et al.  Prediction of relapse or survival in patients with node-negative breast cancer by DNA flow cytometry. , 1989, The New England journal of medicine.

[31]  P. Seeburg,et al.  Tyrosine kinase receptor with extensive homology to EGF receptor shares chromosomal location with neu oncogene. , 1985, Science.

[32]  P. Brown.  Matrix metalloproteinase inhibitors , 2004, Breast Cancer Research and Treatment.

[33]  G. Liljegren,et al.  Topoisomerase II-α Expression in Different Cell Cycle Phases in Fresh Human Breast Carcinomas , 2002, Modern Pathology.

[34]  K S Panageas,et al.  Weekly trastuzumab and paclitaxel therapy for metastatic breast cancer with analysis of efficacy by HER2 immunophenotype and gene amplification. , 2001, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[35]  R. Sutherland,et al.  Inducible overexpression of cyclin D1 in breast cancer cells reverses the growth-inhibitory effects of antiestrogens. , 1997, Clinical cancer research : an official journal of the American Association for Cancer Research.

[36]  M. Mattern,et al.  Proliferation- and cell cycle-dependent differences in expression of the 170 kilodalton and 180 kilodalton forms of topoisomerase II in NIH-3T3 cells. , 1991, Cell growth & differentiation : the molecular biology journal of the American Association for Cancer Research.

[37]  F. Collins,et al.  The Human Genome Project: Lessons from Large-Scale Biology , 2003, Science.

[38]  Shen-Liang Chen,et al.  p53 is a regulator of the metastasis suppressor gene Nm23‐H1 , 2003, Molecular carcinogenesis.

[39]  P. Athanassiadou,et al.  DNA Topoisomerase II-Alpha Immunoreactivity as a Marker of Tumor Aggressiveness in Invasive Breast Cancer , 2000, Pathobiology.

[40]  Qifeng Yang,et al.  Clinicopathological Significance of Vascular Endothelial Growth Factor-C in Breast Carcinoma with Long-Term Follow-Up , 2003, Modern Pathology.

[41]  S. Jiang,et al.  Role of vascular endothelial growth factor in the stimulation of cellular invasion and signaling of breast cancer cells. , 2001, Cell growth & differentiation : the molecular biology journal of the American Association for Cancer Research.

[42]  E. Kawasaki,et al.  Accumulation of p53 tumor suppressor gene protein: an independent marker of prognosis in breast cancers. , 1992, Journal of the National Cancer Institute.

[43]  J. Abrams,et al.  Loss of nm23 expression predicts distal metastases and poorer survival for breast cancer. , 2001, International journal of oncology.

[44]  L. Liotta,et al.  Augmentation of type IV collagenase, laminin receptor, and Ki67 proliferation antigen associated with human colon, gastric, and breast carcinoma progression. , 1991, Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc.

[45]  V. Zurawski,et al.  Comparison of circulating CA15-3 and carcinoembryonic antigen levels in patients with breast cancer. , 1986, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[46]  G. Zambetti,et al.  Inhibition of DNA topoisomerase II alpha gene expression by the p53 tumor suppressor , 1997, Molecular and cellular biology.

[47]  N. Osheroff.  Biochemical basis for the interactions of type I and type II topoisomerases with DNA. , 1989, Pharmacology & therapeutics.

[48]  U. Moll,et al.  Mr 92,000 Type IV Collagenase Is Increased in Plasma of Patients with Colon Cancer and Breast Cancer , 1993 .

[49]  W. McGuire,et al.  Overexpression of HER-2/neu and its relationship with other prognostic factors change during the progression of in situ to invasive breast cancer. , 1992, Human pathology.

[50]  D. Cameron,et al.  Pathological features of breast cancer response following neoadjuvant treatment with either letrozole or tamoxifen. , 2003, European journal of cancer.

[51]  K. Sugimachi,et al.  Clinical significance of vascular endothelial growth factor‐C (VEGF‐C) in breast cancer , 2001, Breast Cancer Research and Treatment.

[52]  I. Ellis,et al.  Ki67 immunostaining in primary breast cancer: pathological and clinical associations. , 1989, British Journal of Cancer.

[53]  B. Bay,et al.  Progesterone induces focal adhesion in breast cancer cells MDA-MB-231 transfected with progesterone receptor complementary DNA. , 2000, Molecular endocrinology.

[54]  H. Joensuu,et al.  Bcl-2 protein expression and long-term survival in breast cancer. , 1994, The American journal of pathology.

[55]  P Boracchi,et al.  Clinical significance of cyclin D1 expression in patients with node-positive breast carcinoma treated with adjuvant therapy. , 1996, Annals of oncology : official journal of the European Society for Medical Oncology.

[56]  Y. Sagara,et al.  Overexpression of cyclinD1 predicts for poor prognosis in estrogen receptor‐negative breast cancer patients , 2002, International journal of cancer.

[57]  J. Wang-Rodriguez,et al.  Male Breast Carcinoma: Correlation of ER, PR, Ki-67, Her2-Neu, and p53 with Treatment and Survival, a Study of 65 Cases , 2002, Modern Pathology.

[58]  M. Hengstschläger,et al.  Specific transformation abolishes cyclin D1 fluctuation throughout the cell cycle , 1996, FEBS letters.

[59]  M. Watson,et al.  Mammaglobin expression in primary, metastatic, and occult breast cancer. , 1999, Cancer research.

[60]  M. Dimopoulos,et al.  G‐CSF induces elevation of circulating CA 15‐3 in breast carcinoma patients treated in an adjuvant setting , 2001, Cancer.

[61]  G. Zupi,et al.  Bcl‐2 overexpression and hypoxia synergistically act to modulate vascular endothelial growth factor expression and in vivo angiogenesis in a breast carcinoma line , 2000, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[62]  D. Beach,et al.  Proliferating cell nuclear antigen and p21 are components of multiple cell cycle kinase complexes. , 1993, Molecular biology of the cell.

[63]  E. Schmidt,et al.  Rate-limiting effects of Cyclin D1 in transformation by ErbB2 predicts synergy between herceptin and flavopiridol. , 2002, Cancer research.

[64]  J. Müller-Brand,et al.  Clinical value of a mucin-like carcinoma-associated antigen in monitoring breast cancer patients in comparison with CA 15-3. , 1991, European journal of cancer.

[65]  T. Ouchi,et al.  BRCA1 regulates p53-dependent gene expression. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[66]  J. Wojtacki,et al.  Evaluation of CA 15-3 tumor marker in the diagnosis of breast cancer. A pilot study. , 1994, Neoplasma.

[67]  H. Preisler,et al.  Amplification and overexpression of topoisomerase IIalpha predict response to anthracycline-based therapy in locally advanced breast cancer. , 2002, Clinical cancer research : an official journal of the American Association for Cancer Research.

[68]  D. W. Green,et al.  HER2/neu antisense targeting of human breast carcinoma , 2000, Oncogene.

[69]  D. Horsfall,et al.  Cyclin DI amplification is not associated with reduced overall survival in primary breast cancer but may predict early relapse in patients with features of good prognosis. , 1996, Clinical cancer research : an official journal of the American Association for Cancer Research.

[70]  B. Angus,et al.  Determination of the prognostic value of cyclin D1 overexpression in breast cancer. , 1995, Oncogene.

[71]  Rebecca Lynn Johnson,et al.  Topoisomerase IIα Expression in Breast Cancer: Correlation with Outcome Variables , 2000, Modern Pathology.

[72]  M. Provencio,et al.  Detection of epithelial messenger RNA in the plasma of breast cancer patients is associated with poor prognosis tumor characteristics. , 2001, Clinical cancer research : an official journal of the American Association for Cancer Research.

[73]  D. Noh,et al.  Abnormal expression of four novel molecular markers represents a highly aggressive phenotype in breast cancer. Immunohistochemical assay of p53, nm23, erbB‐2, and cathepsin D protein , 1997, Journal of surgical oncology.

[74]  R. Abe,et al.  The role of bcl-2 expression in breast carcinomas (Review). , 1998, Oncology reports.

[75]  W. Yung,et al.  Inhibition of breast cancer growth in vivo by antiangiogenesis gene therapy with adenovirus-mediated antisense-VEGF , 2001, British Journal of Cancer.

[76]  P. Khatri,et al.  Global functional profiling of gene expression ? ? This work was funded in part by a Sun Microsystem , 2003 .

[77]  M. Duffy,et al.  High Levels of Cathepsin B Predict Poor Outcome in Patients with Breast Cancer , 1998, The International journal of biological markers.

[78]  M. Merino,et al.  Overexpression of cyclin D mRNA distinguishes invasive and in situ breast carcinomas from non-malignant lesions , 1995, Nature Medicine.

[79]  G. Bastert,et al.  Analysis of sensitivity and specificity of cytokeratin 19 reverse transcriptase/polymerase chain reaction for detection of occult breast cancer in bone marrow and leukapheresis products , 1999, Journal of Cancer Research and Clinical Oncology.

[80]  N. Brünner,et al.  Pooled analysis of prognostic impact of urokinase-type plasminogen activator and its inhibitor PAI-1 in 8377 breast cancer patients. , 2002, Journal of the National Cancer Institute.

[81]  L. Skoog,et al.  The role of cathepsin D and PAI-1 in primary invasive breast cancer as prognosticators and predictors of treatment benefit with adjuvant tamoxifen. , 2000, European journal of cancer.

[82]  W. McGuire,et al.  How to integrate steroid hormone receptor, flow cytometric, and other prognostic information in regard to primary breast cancer , 1993, Cancer.

[83]  G. Ho,et al.  Progestins inhibit the growth of MDA-MB-231 cells transfected with progesterone receptor complementary DNA. , 1999, Clinical cancer research : an official journal of the American Association for Cancer Research.

[84]  P. Steeg,et al.  Site-directed Mutagenesis of nm23-H1 , 1996, The Journal of Biological Chemistry.

[85]  Jorma Isola,et al.  Characterization of topoisomerase IIα gene amplification and deletion in breast cancer , 1999 .

[86]  Thomas Hawighorst,et al.  Induction of tumor lymphangiogenesis by VEGF-C promotes breast cancer metastasis , 2001, Nature Medicine.

[87]  L. Liu,et al.  DNA topoisomerases: essential enzymes and lethal targets. , 1994, Annual review of pharmacology and toxicology.

[88]  T. Fleming,et al.  Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2. , 2001, The New England journal of medicine.

[89]  M. Ashburner,et al.  Gene Ontology: tool for the unification of biology , 2000, Nature Genetics.

[90]  L. Liu,et al.  A homogeneous type II DNA topoisomerase from HeLa cell nuclei. , 1981, The Journal of biological chemistry.

[91]  B. Ljung,et al.  The HER2 (c-erbB-2) oncogene is frequently amplified in in situ carcinomas of the breast. , 1992, Oncogene.

[92]  J. Raemaekers,et al.  Progesterone receptor activity and relapse-free survival in patients with primary breast cancer: The role of adjuvant chemotherapy , 1988, Breast Cancer Research and Treatment.

[93]  H. Guo,et al.  The human tumor cell-derived collagenase stimulatory factor (renamed EMMPRIN) is a member of the immunoglobulin superfamily. , 1995, Cancer research.

[94]  H. Tanaka,et al.  Two isotypes of murine nm23/nucleoside diphosphate kinase, nm23-M1 and nm23-M2, are involved in metastatic suppression of a murine melanoma line. , 1995, Cancer research.

[95]  M. Duffy,et al.  CA 15–3: A Prognostic Marker in Breast Cancer , 2000, The International journal of biological markers.

[96]  Yudong D. He,et al.  A Gene-Expression Signature as a Predictor of Survival in Breast Cancer , 2002 .

[97]  M. Daidone,et al.  Clinical studies of Bcl-2 and treatment benefit in breast cancer patients. , 1999, Endocrine-related cancer.

[98]  A. Harris,et al.  Expression of vascular endothelial growth factor by macrophages is up‐regulated in poorly vascularized areas of breast carcinomas , 2000, The Journal of pathology.

[99]  D. Sliva,et al.  Protein Kinase C Induces Motility of Breast Cancers by Upregulating Secretion of Urokinase-Type Plasminogen Activator through Activation of AP-1 and NF-κB , 2002 .

[100]  B. Loftus,et al.  Breast carcinoma kinetics. Argyrophilic nucleolar organizer region counts correlate with Ki67 scores. , 1989, American journal of clinical pathology.

[101]  H. Rochefort.  Cathepsin D in breast cancer , 1990, Breast Cancer Research and Treatment.

[102]  M. King,et al.  Familial male breast cancer is not linked to the BRCA1 locus on chromosome 17q , 1994, Nature Genetics.

[103]  P. Stanton,et al.  The value of the human epidermal growth factor receptor-2 (HER2) as a prognostic marker. , 2001, European journal of cancer.

[104]  R. Mason,et al.  Quantification of cathepsins B and L in cells. , 1998, The Biochemical journal.

[105]  P. Ingrand,et al.  Prognostic impact of cathepsin D and c-erbB-2 oncoprotein in a subgroup of node-negative breast cancer patients with low histological grade tumors. , 2001, International journal of oncology.

[106]  M. J. van de Vijver,et al.  Breast cancer response to neoadjuvant chemotherapy: predictive markers and relation with outcome , 2003, British Journal of Cancer.

[107]  J. Reynolds,et al.  A fibrosarcoma model derived from mouse embryo cells: Growth properties and secretion of collagenase and metalloproteinase inhibitor (TIMP) by tumour cell lines , 1984, International journal of cancer.

[108]  J. Foekens,et al.  Cytokine‐regulated urokinase‐type‐plasminogen‐activator (uPA) production by human breast fibroblasts in vitro , 1999, Breast Cancer Research and Treatment.

[109]  D. Barnes,et al.  Cyclin D1 in Breast Cancer , 2004, Breast Cancer Research and Treatment.

[110]  David L. Page,et al.  Decreased expression of BRCA1 accelerates growth and is often present during sporadic breast cancer progression , 1995, Nature Genetics.

[111]  N. Ferrara,et al.  The biology of vascular endothelial growth factor. , 1997, Endocrine reviews.

[112]  W. McGuire,et al.  Association of the 323/A3 surface glycoprotein with tumor characteristics and behavior in human breast cancer. , 1990, Cancer research.

[113]  D. Slamon,et al.  Transformation mediated by the human HER-2 gene independent of the epidermal growth factor receptor. , 1992, Oncogene.

[114]  L. Skoog,et al.  p53 expression and the result of adjuvant therapy of breast cancer. , 1995, Acta oncologica.

[115]  K. Sugimachi,et al.  RT-PCR detection of breast cancer cells in sentinel lymph modes. , 2000, International journal of oncology.

[116]  N. Brünner,et al.  The urokinase plasminogen activator system as a target for prognostic studies in breast cancer , 2004, Breast Cancer Research and Treatment.

[117]  J. Bartek,et al.  PATTERNS OF EXPRESSION OF KERATIN 19 AS DETECTED WITH MONOCLONAL ANTIBODIES IN HUMAN BREAST TISSUES AND TUMOURS , 1985, International journal of cancer.

[118]  Herman Yeger,et al.  Decreased levels of the cell-cycle inhibitor p27Kip1 protein: Prognostic implications in primary breast cancer , 1997, Nature Medicine.

[119]  Lawrence C. Brody,et al.  BRCA1 regulates the G2/M checkpoint by activating Chk1 kinase upon DNA damage , 2002, Nature Genetics.

[120]  Jiandong Chen,et al.  Transcriptional Repression of the Anti-apoptoticsurvivin Gene by Wild Type p53* , 2002, The Journal of Biological Chemistry.

[121]  J. Bernheim,et al.  Topoisomerase IIalpha expression in ductal carcinoma in situ of the breast: a preliminary study. , 2000, Human pathology.

[122]  J. Marks,et al.  Maintenance of p53 alterations throughout breast cancer progression. , 1991, Cancer research.

[123]  B. Teicher,et al.  DNA Topoisomerase II α Expression Is Associated with Alkylating Agent Resistance , 1995 .

[124]  G. Clark.  Should selection of adjuvant chemotherapy for patients with breast cancer be based on erbB-2 status? , 1998, Journal of the National Cancer Institute.

[125]  M. Monden,et al.  Bone marrow micrometastases detected by RT-PCR for mammaglobin can be an alternative prognostic factor of breast cancer , 2001, Breast Cancer Research and Treatment.

[126]  P. Steeg,et al.  Inhibition of cell motility after nm23 transfection of human and murine tumor cells. , 1993, Cancer research.

[127]  M. Karkkainen,et al.  Vascular endothelial growth factor C promotes tumor lymphangiogenesis and intralymphatic tumor growth. , 2001, Cancer research.

[128]  J. Bartek,et al.  Amplification and overexpression of cyclin D1 in breast cancer detected by immunohistochemical staining. , 1994, Cancer research.

[129]  I. Bièche,et al.  Prognostic value of CCND1 gene status in sporadic breast tumours, as determined by real-time quantitative PCR assays , 2002, British Journal of Cancer.

[130]  M. Duffy,et al.  Plasminogen activator inhibitor type 2 in breast cancer. , 1997, British Journal of Cancer.

[131]  J. Brisson,et al.  Cathepsin D expression by cancer and stromal cells in breast cancer: an immunohistochemical study of 1348 cases , 1999, Breast Cancer Research and Treatment.

[132]  K. Grandien,et al.  Printed in U.S.A. Copyright © 1997 by The Endocrine Society Comparison of the Ligand Binding Specificity and Transcript Tissue Distribution of Estrogen Receptors � and � , 2022 .

[133]  M. Daidone,et al.  p53 and bcl-2 expression correlates with clinical outcome in a series of node-positive breast cancer patients. , 1996, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[134]  S. Kitazawa,et al.  Serum matrix metalloproteinase‐2 and its density in men with prostate cancer as a new predictor of disease extension , 1998, International journal of cancer.

[135]  M. Lippman,et al.  Quantitative estrogen receptor analyses: The response to endocrine and cytotoxic chemotherapy in human breast cancer and the disease‐free interval , 1980, Cancer.

[136]  Martin Eisenacher,et al.  Cytogenetic Alterations and Cytokeratin Expression Patterns in Breast Cancer: Integrating a New Model of Breast Differentiation into Cytogenetic Pathways of Breast Carcinogenesis , 2002, Laboratory Investigation.

[137]  R. Kumar,et al.  The role of HER2 in angiogenesis. , 2001, Seminars in oncology.

[138]  J. Oh,et al.  Up-regulation of urokinase-type plasminogen activator by insulin-like growth factor-I depends upon phosphatidylinositol-3 kinase and mitogen-activated protein kinase kinase. , 2001, Cancer research.

[139]  M. Gellert,et al.  Mechanistic aspects of DNA topoisomerases. , 1986, Advances in protein chemistry.

[140]  J. Schneider,et al.  Accumulation of uPA – PAI-1 complexes inside the tumour cells is associated with axillary nodal invasion in progesterone-receptor-positive early breast cancer , 2003, British Journal of Cancer.

[141]  N. Weidner,et al.  Correlation of Ki-67 antigen expression with mitotic figure index and tumor grade in breast carcinomas using the novel "paraffin"-reactive MIB1 antibody. , 1994, Human pathology.

[142]  F. Balkwill,et al.  IL‐12 regulates VEGF and MMPs in a murine breast cancer model , 1998, International journal of cancer.

[143]  R. Paridaens,et al.  A real-time quantitative reverse transcriptase polymerase chain reaction (RT-PCR) to detect breast carcinoma cells in peripheral blood , 2001 .

[144]  C. Bird,et al.  Production of collagenase and inhibitor (TIMP) by intracranial tumors and dura in vitro. , 1983, Journal of neurosurgery.

[145]  P. Steeg,et al.  Nm23-H1: genetic alterations and expression patterns in tumor metastasis. , 1998, American journal of human genetics.

[146]  S. West,et al.  Distinct functions of BRCA1 and BRCA2 in double-strand break repair , 2001, Breast Cancer Research.

[147]  J. Robertson,et al.  CA27.29: a valuable marker for breast cancer management. A confirmatory multicentric study on 603 cases. , 2001, European journal of cancer.

[148]  D. Wallwiener,et al.  Prognostic relevance of cathepsin D detection in micrometastatic cells in the bone marrow of patients with primary breast cancer , 1998, Breast Cancer Research and Treatment.

[149]  B. Coulombe,et al.  Decreased expression of tissue inhibitor of metalloproteinases in metastatic tumor cells leading to increased levels of collagenase activity. , 1991, Cancer research.

[150]  S. Cowley,et al.  Estrogen Receptors α and β Form Heterodimers on DNA* , 1997, The Journal of Biological Chemistry.

[151]  G. Landberg,et al.  Deregulation of cyclin E and D1 in breast cancer is associated with inactivation of the retinoblastoma protein , 1997, Oncogene.

[152]  D. Goeddel,et al.  Vascular endothelial growth factor is a secreted angiogenic mitogen. , 1989, Science.

[153]  K. Alitalo,et al.  Vascular endothelial growth factor D (VEGF-D) is a ligand for the tyrosine kinases VEGF receptor 2 (Flk1) and VEGF receptor 3 (Flt4). , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[154]  M. Ewen,et al.  Cyclin D1 stimulation of estrogen receptor transcriptional activity independent of cdk4 , 1997, Molecular and cellular biology.

[155]  G. Opdenakker,et al.  Chemotactic factors, passive invasion and metastasis of cancer cells. , 1992, Immunology today.

[156]  S. Rabbani,et al.  Transcriptional regulation of urokinase (uPA) gene expression in breast cancer cells: Role of DNA methylation. , 1999, International journal of cancer.

[157]  M. Espié,et al.  Is p53 a protein that predicts the response to chemotherapy in node negative breast cancer? , 2004, Breast Cancer Research and Treatment.

[158]  J. Isola,et al.  Predictive value of topoisomerase IIalpha and other prognostic factors for epirubicin chemotherapy in advanced breast cancer. , 1998, British Journal of Cancer.

[159]  J. Holden,et al.  DNA topoisomerase II-alpha as a proliferation marker in astrocytic neoplasms of the central nervous system: correlation with MIB1 expression and patient survival. , 1999, Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc.

[160]  S. Elledge,et al.  Cyclin D1 provides a link between development and oncogenesis in the retina and breast , 1995, Cell.

[161]  C. Clarke,et al.  Absence of progesterone receptor associated with secondary breast cancer in postmenopausal women , 1999, British Journal of Cancer.

[162]  Douglas M. Evans,et al.  Maximum Effect of Urokinase Plasminogen Activator Inhibitors in the Control of Invasion and Metastasis of Rat Mammary Cancer , 1998, Invasion and Metastasis.

[163]  M. Vijver,et al.  Assessment of the need and appropriate method for testing for the human epidermal growth factor receptor-2 (HER2). , 2001 .

[164]  C. Hudis,et al.  Phase II study of weekly intravenous trastuzumab (Herceptin) in patients with HER2/neu-overexpressing metastatic breast cancer. , 1999, Seminars in oncology.

[165]  Y. Niu,et al.  Potential markers predicting distant metastasis in axillary node‐negative breast carcinoma , 2002, International journal of cancer.

[166]  V. Vetvicka,et al.  Analysis of the interaction of procathepsin D activation peptide with breast cancer cells , 1997, International journal of cancer.

[167]  L. Devy,et al.  Down-regulation of vascular endothelial growth factor by tissue inhibitor of metalloproteinase-2: effect on in vivo mammary tumor growth and angiogenesis. , 2001, Cancer research.

[168]  M. Fiegl,et al.  Mammaglobin Gene Expression: A Superior Marker of Breast Cancer Cells in Peripheral Blood in Comparison to Epidermal-Growth-Factor Receptor and Cytokeratin-19 , 2000, Laboratory Investigation.

[169]  A. Marchetti,et al.  Cyclin‐d1‐gene amplification and expression in breast carcinoma: Relation with clinicopathologic characteristics and with retinoblastoma gene product, p53 and p21waf1 immunohistochemical expression , 1997, International journal of cancer.

[170]  I. Nishimoto,et al.  Prognostic Significance of the Combined Expression of Matrix Metalloproteinase-9, Urokinase Type Plasminogen Activator and its Receptor in Breast Cancer as Measured by Northern Blot Analysis , 2001, The International journal of biological markers.

[171]  K. Alitalo,et al.  VEGF-C receptor binding and pattern of expression with VEGFR-3 suggests a role in lymphatic vascular development. , 1996, Development.

[172]  H. Herz,et al.  Metastatic secretory breast cancer. Non-responsiveness to chemotherapy: case report and review of the literature. , 2000, Annals of oncology : official journal of the European Society for Medical Oncology.

[173]  E. Osinaga,et al.  Molecular detection of cancer cells in bone marrow and peripheral blood of patients with operable breast cancer. Comparison of CK19, MUC1 and CEA using RT-PCR. , 2000, European journal of cancer.

[174]  H. Höfler,et al.  Prognostic impact of proteolytic factors (urokinase-type plasminogen activator, plasminogen activator inhibitor 1, and cathepsins B, D, and L) in primary breast cancer reflects effects of adjuvant systemic therapy. , 2001, Clinical cancer research : an official journal of the American Association for Cancer Research.

[175]  K. Alitalo,et al.  Vascular endothelial growth factors VEGF-B and VEGF-C are expressed in human tumors. , 1998, The American journal of pathology.

[176]  D. Evans,et al.  Suppression of pulmonary metastases of rat mammary cancer by recombinant urokinase plasminogen activator inhibitor. , 1995, The American surgeon.

[177]  J. Wang,et al.  Cloning and sequencing of cDNA encoding human DNA topoisomerase II and localization of the gene to chromosome region 17q21-22. , 1988, Proceedings of the National Academy of Sciences of the United States of America.

[178]  R. Muschel,et al.  Induction of fibroblast 92 kDa gelatinase/type IV collagenase expression by direct contact with metastatic tumor cells. , 1994, Journal of cell science.

[179]  J E Talmadge,et al.  Evidence for a novel gene associated with low tumor metastatic potential. , 1988, Journal of the National Cancer Institute.

[180]  M. Hou,et al.  Evaluation of serum CA27.29, CA15-3 and CEA in patients with breast cancer. , 1999, The Kaohsiung journal of medical sciences.

[181]  U. Nannmark,et al.  Matrix metalloproteinases produced by rat IL-2-activated NK cells. , 1998, Journal of immunology.

[182]  O. Bârzu,et al.  Dictyostelium Nucleoside Diphospate Kinase Highly Homologous to Nm23 and Awd Proteins Involved in Mammalian Tumor Metastasis and Drosphila Development , 1990 .

[183]  N. Brünner,et al.  Tumor Tissue Concentrations of the Proteinase Inhibitors Tissue Inhibitor of Metalloproteinases-1 (TIMP-1) and Plasminogen Activator Inhibitor Type 1 (PAI-1) Are Complementary in Determining Prognosis in Primary Breast Cancer * , 2003, Molecular & Cellular Proteomics.

[184]  C. Blomqvist,et al.  Cathepsin-D, urokinase plasminogen activator and type-1 plasminogen activator inhibitor in early breast cancer: an immunohistochemical study of prognostic value and relations to tenascin-C and other factors , 1999, British Journal of Cancer.

[185]  Y. Chen,et al.  BRCA1 is a 220-kDa nuclear phosphoprotein that is expressed and phosphorylated in a cell cycle-dependent manner. , 1996, Cancer research.

[186]  N. Gebbia,et al.  Cathepsin D in the malignant progression of neoplastic diseases (review). , 1992, Anticancer research.

[187]  R. Hildenbrand,et al.  Urokinase plasminogen activator induces angiogenesis and tumor vessel invasion in breast cancer. , 1995, Pathology, research and practice.

[188]  M G Daidone,et al.  Biological markers as indicators of response to primary and adjuvant chemotherapy in breast cancer , 1999, International journal of cancer.

[189]  A. Harris,et al.  High-dose tamoxifen as an enhancer of etoposide cytotoxicity. Clinical effects and in vitro assessment in p-glycoprotein expressing cell lines. , 1992, British Journal of Cancer.

[190]  E. Röttinger,et al.  Comparison of CA 15-3 and CEA in diagnosis and monitoring of breast cancer , 1989, The International journal of biological markers.

[191]  N. Brünner,et al.  Direct evidence of the importance of stromal urokinase plasminogen activator (uPA) in the growth of an experimental human breast cancer using a combined uPA gene-disrupted and immunodeficient xenograft model. , 2001, Cancer research.

[192]  A. Harris,et al.  Topoisomerase II alpha co-amplification with erbB2 in human primary breast cancer and breast cancer cell lines: relationship to m-AMSA and mitoxantrone sensitivity. , 1993, Oncogene.

[193]  M. Duffy,et al.  Urokinase‐plasminogen activator, a marker for aggressive breast carcinomas. Preliminary report , 1988, Cancer.

[194]  C. Sweep,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. , 2001, Journal of the National Cancer Institute.

[195]  J. Andersen.  Determination of Estrogen Receptors in Paraffin-Embedded Tissue: Techniques and the value in breast cancer treatment , 1992 .

[196]  C. Redmond,et al.  Influence of tumor estrogen and progesterone receptor levels on the response to tamoxifen and chemotherapy in primary breast cancer. , 1983, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[197]  J. Downward,et al.  Regulation of MUC1 expression in human mammary cell lines by the c-ErbB2 and ras signaling pathways. , 2001, DNA and cell biology.

[198]  T. Kurizaki,et al.  Relationship between matrix metalloproteinase expression and tumor angiogenesis in human breast carcinoma. , 1998, Oncology reports.

[199]  H. Joensuu,et al.  Serum VEGF levels in women with a benign breast tumor or breast cancer , 2004, Breast Cancer Research and Treatment.

[200]  R. Gray,et al.  Accumulation of p53 protein as a possible predictor of response to adjuvant combination chemotherapy with cyclophosphamide, methotrexate, fluorouracil, and prednisone for breast cancer. , 1995, Journal of the National Cancer Institute.

[201]  G. Hortobagyi,et al.  Correlation between HER‐2 expression and response to neoadjuvant chemotherapy with 5‐fluorouracil, doxorubicin, and cyclophosphamide in patients with breast carcinoma , 2003, Cancer.

[202]  A. Blejec,et al.  Cathepsin B, a prognostic indicator in lymph node-negative breast carcinoma patients: comparison with cathepsin D, cathepsin L, and other clinical indicators. , 2000, Clinical cancer research : an official journal of the American Association for Cancer Research.

[203]  K. Alitalo,et al.  Genomic Organization of the Mouse and Human Genes for Vascular Endothelial Growth Factor B (VEGF-B) and Characterization of a Second Splice Isoform* , 1996, The Journal of Biological Chemistry.

[204]  M. Feldstein,et al.  The relative importance of estrogen receptor analysis as a prognostic factor for recurrence or response to chemotherapy in women with breast cancer , 1980, Cancer.

[205]  T. Sauer,et al.  nm23 protein expression in fine‐needle aspirates from breast carcinoma , 1998, Cancer.

[206]  M. Mandalà,et al.  Abnormally enhanced blood concentrations of vascular endothelial growth factor (VEGF) in metastatic cancer patients and their relation to circulating dendritic cells, IL-12 and endothelin-1. , 2001, Journal of biological regulators and homeostatic agents.

[207]  N. Sneige,et al.  Clinical, Histopathologic, and Biologic Features of Pleomorphic Lobular (Ductal-Lobular) Carcinoma In Situ of the Breast: A Report of 24 Cases , 2002 .

[208]  C. Broeckhoven,et al.  Identification of the tumor metastasis suppressor Nm23-H1/Nm23-R1 as a constituent of the centrosome. , 2001, Experimental cell research.

[209]  G. Tuszynski,et al.  Tumour cell thrombospondin-1 regulates tumour cell adhesion and invasion through the urokinase plasminogen activator receptor , 2000, British Journal of Cancer.

[210]  E. Kumpulainen,et al.  Serum Tumor Marker CA 15.3 and Stage are the Two Most Powerful Predictors of Survival in Primary Breast Cancer , 2002, Breast Cancer Research and Treatment.

[211]  G. Lenoir,et al.  Down-regulation of BRCA1 in human sporadic breast cancer; analysis of DNA methylation patterns of the putative promoter region , 1998, Oncogene.

[212]  Timothy B. Stockwell,et al.  The Sequence of the Human Genome , 2001, Science.

[213]  A. Reiner,et al.  Coexpression of HER-2/neu and p53 is associated with a shorter disease-free survival in node-positive breast cancer patients , 2005, Journal of Cancer Research and Clinical Oncology.

[214]  M. Ahmad,et al.  Antisense RNA to the putative tumor suppressor gene BRCA1 transforms mouse fibroblasts. , 1996, Oncogene.

[215]  D. Hanahan,et al.  Switch to the angiogenic phenotype during tumorigenesis. , 1991, Princess Takamatsu symposia.

[216]  H. Rochefort,et al.  Cathepsin D in breast cancer: mechanisms and clinical applications, a 1999 overview. , 2000, Clinica chimica acta; international journal of clinical chemistry.

[217]  J. Ross,et al.  The HER‐2/neu Oncogene in Breast Cancer: Prognostic Factor, Predictive Factor, and Target for Therapy , 1998, The oncologist.

[218]  P. Steeg,et al.  Transfection of human nm23-H1 into the human MDA-MB-435 breast carcinoma cell line: effects on tumor metastatic potential, colonization and enzymatic activity. , 1993, Oncogene.

[219]  M. Pasdar,et al.  The importance of MUC1 cellular localization in patients with breast carcinoma , 2001, Cancer.

[220]  D. Connolly,et al.  Human vascular permeability factor. Isolation from U937 cells. , 1989, The Journal of biological chemistry.

[221]  S. Narod,et al.  RT-PCR amplification of CK19 mRNA in the blood of breast cancer patients: correlation with established prognostic parameters , 2000, Breast Cancer Research and Treatment.

[222]  D. Bouchier-Hayes,et al.  Vascular endothelial growth factor (VEGF) upregulates BCL-2 and inhibits apoptosis in human and murine mammary adenocarcinoma cells , 2001, British Journal of Cancer.

[223]  Fernández,et al.  Cathepsin D in host stromal cells is associated with more highly vascular and aggressive invasive breast carcinoma , 1999, Histopathology.

[224]  S. Sheen-Chen,et al.  Serum levels of matrix metalloproteinase 2 in patients with breast cancer. , 2001, Cancer letters.

[225]  B. Asselain,et al.  Estrogen receptor negative and progesterone receptor positive primary breast cancer: Pathological characteristics and clinical outcome , 1998, Breast Cancer Research and Treatment.

[226]  M. Daidone,et al.  Biomarkers and outcome after tamoxifen treatment in node-positive breast cancers from elderly women , 2000, British Journal of Cancer.

[227]  M. Duffy,et al.  Increased gelatinase‐A and gelatinase‐B activities in malignant vs. benign breast tumors , 2000, International journal of cancer.

[228]  A. Sonnenberg,et al.  Episialin (MUC1) overexpression inhibits integrin-mediated cell adhesion to extracellular matrix components , 1995, The Journal of cell biology.

[229]  J. Champoux.  Mechanism of the reaction catalyzed by the DNA untwisting enzyme: attachment of the enzyme to 3'-terminus of the nicked DNA. , 1978, Journal of molecular biology.

[230]  N. Brünner,et al.  Low cathepsin D and low plasminogen activator type 1 inhibitor in tumor cytosols defines a group of node negative breast cancer patients with low risk of recurrence , 2004, Breast Cancer Research and Treatment.

[231]  M. Monden,et al.  Association of BRCA2 polymorphism at codon 784 (Met/Val) with breast cancer risk and prognosis. , 2003, Clinical cancer research : an official journal of the American Association for Cancer Research.

[232]  F. Révillion,et al.  Prognostic value of the type I growth factor receptors in a large series of human primary breast cancers quantified with a real-time reverse transcription-polymerase chain reaction assay. , 2000, Clinical cancer research : an official journal of the American Association for Cancer Research.

[233]  O. Kallioniemi,et al.  Serum CA 15-3 assay in the diagnosis and follow-up of breast cancer. , 1988, British Journal of Cancer.

[234]  N. J. Wells,et al.  Physiological regulation of eukaryotic topoisomerase II. , 1998, Biochimica et biophysica acta.

[235]  S. Shousha,et al.  High level expression of p27(kip1) and cyclin D1 in some human breast cancer cells: inverse correlation between the expression of p27(kip1) and degree of malignancy in human breast and colorectal cancers. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[236]  M. Dowsett,et al.  Assessment of HER2 status in breast cancer: why, when and how? , 2000, European journal of cancer.

[237]  W. McGuire,et al.  Prognostic factors in breast cancer. , 1989, Hematology/oncology clinics of North America.

[238]  R. Parwaresch,et al.  Human DNA-Topoisomerases – Diagnostic and Therapeutic Implications for Cancer , 2000, Oncology Research and Treatment.

[239]  P. Friedman,et al.  Mammaglobin is found in breast tissue as a complex with BU101. , 2001, Biochemistry.

[240]  J. A. Hamilton,et al.  Expression and amplification of cyclin genes in human breast cancer. , 1993, Oncogene.

[241]  W. McGuire,et al.  Association of p53 protein expression with tumor cell proliferation rate and clinical outcome in node-negative breast cancer. , 1993, Journal of the National Cancer Institute.

[242]  D. Gospodarowicz,et al.  Isolation and characterization of a newly identified endothelial cell mitogen produced by AtT‐20 cells. , 1989, The EMBO journal.

[243]  R. Camplejohn,et al.  DNA flow cytometry and response to preoperative chemotherapy for primary breast cancer. , 1992, European journal of cancer.

[244]  James M. Roberts,et al.  Expression of cell-cycle regulators p27Kip1 and cyclin E, alone and in combination, correlate with survival in young breast cancer patients , 1997, Nature Medicine.

[245]  R. Elledge,et al.  Prognostic and predictive value of p53 and p21 in breast cancer , 2004, Breast Cancer Research and Treatment.

[246]  D M Barnes,et al.  Demystified ... cell cycle. , 1998, Molecular pathology : MP.

[247]  T. Tsangaris,et al.  Tumor hormone receptor status and recurrences in premenopausal patients with node‐negative breast carcinoma , 1992, Cancer.

[248]  C. Osborne,et al.  Cytological evaluation of biological prognostic markers from primary breast carcinomas , 1997, Breast Cancer Research and Treatment.

[249]  J. Weber,et al.  Closing in on a breast cancer gene on chromosome 17q. , 1992, American journal of human genetics.

[250]  Masakazu,et al.  Significance of vascular endothelial growth factor (VEGF)/soluble VEGF receptor‐1 relationship in breast cancer , 2002, International journal of cancer.

[251]  M. de las Heras,et al.  Preoperative values of CA 15-3 and CEA as prognostic factors in breast cancer: a multivariate analysis. , 2001, Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine.

[252]  A. Reymond,et al.  Amplification and overexpression of PRUNE in human sarcomas and breast carcinomas–a possible mechanism for altering the nm23-H1 activity , 2001, Oncogene.

[253]  Philip Smith,et al.  KiSl—A novel monoclonal antibody which recognizes proliferating cells: Evaluation of its relationship to prognosis in mammary carcinoma , 1992, The Journal of pathology.

[254]  N. Brünner,et al.  The complex between urokinase and its type-1 inhibitor in primary breast cancer: relation to survival. , 2000, Cancer research.

[255]  T. Irimura,et al.  Decreased expression of nucleoside diphosphate kinase α isoform, an nm23‐H2 gene homolog, is associated with metastatic potential of rat mammary‐adenocarcinoma cells , 1996, International journal of cancer.

[256]  S. Fox,et al.  VEGF‐B expression in human primary breast cancers is associated with lymph node metastasis but not angiogenesis , 2001, The Journal of pathology.

[257]  G. Hortobagyi,et al.  Breast Cancer in Men , 2002, Annals of Internal Medicine.

[258]  J. Peterse,et al.  A clinicopathological study on overexpression of cyclin D1 and of p53 in a series of 248 patients with operable breast cancer. , 1996, British Journal of Cancer.

[259]  P. Kenemans,et al.  Antibody‐dependent cell‐mediated cytotoxicity can be induced by MUC1 peptide vaccination of breast cancer patients , 2001, International journal of cancer.

[260]  P. Atadja,et al.  Overexpression of cyclin D1 blocks proliferation of normal diploid fibroblasts. , 1995, Experimental cell research.

[261]  O. Zach,et al.  Detection of circulating mammary carcinoma cells in the peripheral blood of breast cancer patients via a nested reverse transcriptase polymerase chain reaction assay for mammaglobin mRNA. , 1999, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[262]  Ruth Etzioni,et al.  Early detection: The case for early detection , 2003, Nature Reviews Cancer.

[263]  M. S. Lakshmi,et al.  Metastasis associated MTS1 and NM23 genes affect tubulin polymerisation in B16 melanomas: a possible mechanism of their regulation of metastatic behaviour of tumours. , 1993, Anticancer research.

[264]  C. Redmond,et al.  Relative worth of estrogen or progesterone receptor and pathologic characteristics of differentiation as indicators of prognosis in node negative breast cancer patients: findings from National Surgical Adjuvant Breast and Bowel Project Protocol B-06. , 1988, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[265]  R. Salgado,et al.  Serum interleukin 6, plasma VEGF, serum VEGF, and VEGF platelet load in breast cancer patients. , 2002, Clinical breast cancer.

[266]  E. Schuuring,et al.  D11S287, a putative oncogene on chromosome 11q13, is amplified and expressed in squamous cell and mammary carcinomas and linked to BCL-1. , 1991, Oncogene.

[267]  M. D. De Latour,et al.  Expression of BRCA1 and BRCA2 in male breast cancers and gynecomastias. , 2003, Anticancer research.

[268]  J Chang-Claude,et al.  Genetic heterogeneity and penetrance analysis of the BRCA1 and BRCA2 genes in breast cancer families. The Breast Cancer Linkage Consortium. , 1998, American journal of human genetics.

[269]  J. Crow,et al.  The role of p53 and Ki67 in Paget's disease of the vulva and the breast. , 2002, Gynecologic oncology.

[270]  R. Nicosia.  What is the role of vascular endothelial growth factor-related molecules in tumor angiogenesis? , 1998, The American journal of pathology.

[271]  R. Narayan,et al.  Anti-Urokinase-Type Plasminogen Activator Monoclonal Antibodies Inhibit the Proliferation of Human Breast Cancer Cell Lines in vitro , 1998, Tumor Biology.

[272]  D. Slamon,et al.  HER-2/neu gene amplification characterized by fluorescence in situ hybridization: poor prognosis in node-negative breast carcinomas. , 1997, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[273]  Stephen Safe,et al.  Transcriptional activation of cathepsin D gene expression by 17β-estradiol: mechanism of aryl hydrocarbon receptor-mediated inhibition , 2001, Molecular and Cellular Endocrinology.

[274]  T. Powles,et al.  p53 protein overexpression and chemosensitivity in breast cancer , 1995, The Lancet.

[275]  C. Osborne,et al.  bcl-2, p53, and response to tamoxifen in estrogen receptor-positive metastatic breast cancer: a Southwest Oncology Group study. , 1997, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[276]  S. Kyin,et al.  Catalysis of DNA cleavage and nucleoside triphosphate synthesis by NM23-H2/NDP kinase share an active site that implies a DNA repair function. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[277]  J. Kurebayashi,et al.  Expression of Vascular Endothelial Growth Factor (VEGF) Family Members in Breast Cancer , 1999, Japanese journal of cancer research : Gann.

[278]  P Boracchi,et al.  Expression of bcl-2 protein predicts efficacy of adjuvant treatments in operable node-positive breast cancer. , 1995, Clinical cancer research : an official journal of the American Association for Cancer Research.

[279]  C. Scopa,et al.  Microvessel density, proliferating activity, p53 and bcl-2 expression in in situ ductal carcinoma of the breast. , 1999, Anticancer research.

[280]  W. McGuire,et al.  Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene. , 1987, Science.

[281]  M. Watson,et al.  Mammaglobin, a Breast‐Specific Gene, and Its Utility as a Marker for Breast Cancer , 2000, Annals of the New York Academy of Sciences.

[282]  A. Schneeweiss,et al.  P53 is the strongest predictor of survival in high‐risk primary breast cancer patients undergoing high‐dose chemotherapy with autologous blood stem cell support , 2002, International journal of cancer.

[283]  M. Mai,et al.  Amplification of the c-erbB-2 (HER-2/neu) gene in gastric cancer cells. Detection by fluorescence in situ hybridization. , 1997, The American journal of pathology.

[284]  G. Peters,et al.  Cyclin D1 and prognosis in human breast cancer , 1996, International journal of cancer.

[285]  G. Peters,et al.  Characterization and chromosome assignment of the human homolog of int-2, a potential proto-oncogene , 1986, Molecular and cellular biology.

[286]  Z. Su,et al.  Defining the critical gene expression changes associated with expression and suppression of the tumorigenic and metastatic phenotype in Ha-ras-transformed cloned rat embryo fibroblast cells. , 1993, Oncogene.

[287]  W. R. Bishop,et al.  Human survivin is negatively regulated by wild-type p53 and participates in p53-dependent apoptotic pathway , 2002, Oncogene.

[288]  D. Generali,et al.  Changes in microvessel density as assessed by CD34 antibodies after primary chemotherapy in human breast cancer. , 2002, Clinical cancer research : an official journal of the American Association for Cancer Research.

[289]  John Calvin Reed,et al.  Prognostic significance of apoptosis regulators in breast cancer. , 1999, Endocrine-related cancer.

[290]  R. Weinberg,et al.  Transforming genes of carcinomas and neuroblastomas introduced into mouse fibroblasts , 1981, Nature.

[291]  R. Young,et al.  BRCA1 is a component of the RNA polymerase II holoenzyme. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[292]  D. Easton,et al.  Allele losses in the region 17q12–21 in familial breast and ovarian cancer involve the wild–type chromosome , 1992, Nature Genetics.

[293]  G. Bevilacqua,et al.  Decreasing expression of NM23 gene in metastatic murine mammary tumors of viral etiology (MMTV). , 1992, Anticancer research.

[294]  H. Grimes,et al.  The Prognostic Value of the Tumor Marker CA 15–3 at Initial Diagnosis of Patients with Breast Cancer , 2000, The International journal of biological markers.

[295]  Å. Borg,et al.  Amplification and deletion of topoisomerase IIalpha associate with ErbB-2 amplification and affect sensitivity to topoisomerase II inhibitor doxorubicin in breast cancer. , 2000, The American journal of pathology.

[296]  L. Riley,et al.  Analysis of cathepsin D in human breast cancer: Usefulness of the processsed 31 kDa active form of the enzyme as a prognostic indicator in node-negative and node-positive patients , 2000, Breast Cancer Research and Treatment.

[297]  M. Erdos,et al.  BRCA1 inhibition of estrogen receptor signaling in transfected cells. , 1999, Science.

[298]  N. Lemoine,et al.  Proliferative index in breast carcinoma determined in situ by Ki67 immunostaining and its relationship to clinical and pathological variables , 1987, The Journal of pathology.

[299]  M. Lippman,et al.  BRCA1 and BRCA2 in breast cancer , 1999, Breast Cancer Research and Treatment.

[300]  W. McGuire,et al.  Prognostic significance of progesterone receptor levels in estrogen receptor-positive patients with metastatic breast cancer treated with tamoxifen: results of a prospective Southwest Oncology Group study. , 1992, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[301]  M Monden,et al.  Selection of mRNA markers for detection of lymph node micrometastases in breast cancer patients. , 2000, Oncology reports.

[302]  D. Berger,et al.  Role of urokinase plasminogen activator receptor in thrombospondin 1-mediated tumor cell invasion. , 1999, The Journal of surgical research.

[303]  M. Nakajima,et al.  Transforming growth factor beta stimulates mammary adenocarcinoma cell invasion and metastatic potential. , 1990, Proceedings of the National Academy of Sciences of the United States of America.

[304]  T. Kitamoto,et al.  Molecular Mechanism of a Cross-Talk between Estrogen and Growth-Factor Signaling Pathways , 1998, Oncology.

[305]  D. Larsimont,et al.  HER-2 amplification and topoisomerase IIalpha gene aberrations as predictive markers in node-positive breast cancer patients randomly treated either with an anthracycline-based therapy or with cyclophosphamide, methotrexate, and 5-fluorouracil. , 2002, Clinical cancer research : an official journal of the American Association for Cancer Research.

[306]  Takuma Sasaki,et al.  Inverse Correlation between mRNA Expression of Plasminogen Activator Inhibitor‐2 and Lymph Node Metastasis in Human Breast Cancer , 1996, Japanese journal of cancer research : Gann.

[307]  J. Roh,et al.  Different expression patterns of MMP-2 and MMP-9 in breast cancer. , 1998, Oncology reports.