Methods of cancer diagnosis, therapy and prognosis : breast carcinoma

1. BREAST CANCER: COMPUTER-AIDED DETECTION Bin Zheng INTRODUCTION DEVELOPMENT OF COMPUTER-AIDED DETECTION SCHEMES EVALUATION OF COMPUTER-AIDED DETECTION SCHEME PERFORMANCE APPLICATION OF COMPUTER-AIDED DETECTION SCHEMES TO CLINICAL ENVIRONMENT NEW DEVELOPMENTS IN COMPUTER-AIDED DETECTION RESEARCH REFERENCES 2. SEBACEOUS CARCINOMA OF THE BREAST: CLINICOPATHOLOGIC FEATURES INTRODUCTION METHODS CLINICAL FEATURES PATHOLOGIC FINDINGS DIFFERENTIAL DIAGNOSIS PROGNOSIS AND TREATMENT REFRENCES 3. BREAST CANCER: DETECTION BY IN VIVO IMAGING OF ANGIOGENESIS Tore Bach-Gansmo and Derek Tobin INTRODUCTION ANGIOGENESIS INTEGRINS SCINTIMAMMOGRAPHY TECHNETIUM-LABELED NC100692 INITIAL CLINICAL EXPERIENCE 99mTc-NC100692 IN BREAST CANCER IMPROVEMENTS IN GAMMA CAMERA TECHNOLOGY SUPPLEMENTARY CLINICAL STUDY FUTURE INTEGRIN SCINTIGRAPHY REFERENCES 4. BREAST AND PROSTATE BIOPSIES: USE OF OPTIMIZED HIGH-THROUGHPUT MicroRNA EXPRESSION FOR DIAGNOSIS (METHODOLOGY) Michael D. Mattie and Robert C. Getts INTRODUCTION METHODOLOGY FOR HIGH-THROUGHPUT microRNA PROFILING Purification of microRNA AMPLIFICATION OF LOW MOLECULAR WEIGHT RNA LABELING OF microRNA REFERENCES 5. FAMILIAL BREAST CANCER: DETECTION OF PREVALENT HIGH-RISK EPITHELIAL LESIONS Peter Bult and Nicoline Hoogerbrugge INTRODUCTION MATERIALS METHODS CLASSIFICATION OF PREMALIGNANT LESIONS REFERENCES 6. DIFFERENTIATION BETWEEN BENIGN AND MALIGNANT PAPILLARY LESIONS OF THE BREAST: EXCISIONAL BIOPSY OR STEREOTACTIC VACUUM-ASSISTED BIOPSY (METHODOLOGY) Alice P.Y. Tang, Gary M.K. Tse, and Wynnie W.M. Lam INTRODUCTION RADIOLOGICAL APPEARANCE OF PAPPILARY LESIONS OF THE BREAST PATHOLOGICAL FINDINGS ASSOCIATION OF PAPPILARY LESIONS WITH DUCTAL CARCINOMA FINE NEEDLE ASPIRATION CORE NEEDLE BIOPSY CURRENT ROLE OF EXCISIONAL BIOPSY DIFFICULTY IN PATHOLOGICAL DIFFERENTIATION BETWEEN MALIGNANT AND BENIGN LESIONS AFTER NEEDLE BIOPSY VACCUM-ASSISTED BIOPSY TECHNIQUE OF STEREOTACTIC VACCUM-ASSISTED BIOPSY TECHNIQUE OF ULTRASOUND-GUIDED VACCUM-ASSISTED BIOPSY ADVANTAGES OF DIRECTIONAL VACCUM-ASSISTED DEVICE COMPLICATIONS OF VACCUM ASSISTED BIOPSY CURRENT EXPERIENCE OF VACCUM-ASSISTED BIOPSY AND PERCUTANEOUS CORE BIOPSY IN THE MANAGEMENT OF PAPPILARY LESIONS IS EXCISION BIOPSY NEEDED IN ASSESSING PAPPILARY LESIONS OF THE BREAST ATYPICAL PAPILLOMA/ PAPILLARY LESION WITH ATYPICAL DUCTAL HYPERPLASIA AT VACCUM-ASSISTED BIOPSY BENIGN PAPILLOMA AT VACCUM-ASSISTED BIOPSY REFERENCES 7. MULTICENTRIC BREAST CANCER: SENTINEL NODE BIOPSY AS A DIAGNOSTIC TOOL Michael Knauer, Peter Konstantiniuk, Anton Haid, Etienne Wenzl, Roswitha Koberle-Wuhrer, Michaela Riegler-Keil, Sabine Postlberger, Roland Reitsamer, and Peter Schrenk INTRODUCTION TECHNIQUE OF SENTINEL NODE BIOPSY IN MULTICENTRIC BREAST CANCER Technique of Lymphatic Mapping Histologic Evaluation of Sentinel Nodes Surgical Procedures RESULTS OF THE AUSTRIAN SENTINEL NODE STUDY GROUP Patients and Data Follow-up DISCUSSION Clinical Advantage of Sentinel Node Biopsy in Multicentric Breast Cancer Quality Control of Sentinel Node Biopsy Procedure REFERENCES 8. BREAST CANCER RECURRENCE: ROLE OF SERUM TUMOR MARKERS CEA AND CA 15-3 (METHODOLOGY) Franco Lumachi, Stefano M.M. Basso, and Umberto Basso INTRODUCTION SERUM TUMOR MARKERS AND BREAST CANCER CARCINOEMBRYONIC ANTIGEN CANCER ANTIGEN 15-3 PREDICTION OF RISK OF RECURRENCE AND LOCOREGIONAL RELAPSE MONITORING THE RESPONSE TO THERAPY OF RECURRENCES CONCLUSIONS REFERENCEs 9. BREAST CANCER PATIENTS BEFORE, DURING OR AFTER TREATMENT: CIRCULATING TUMOR CELLS IN PERIPHERAL BLOOD DETECTED BY MULTIGENE REAL- TIME REVERSE TRANSCRIPTASE-POLYMERASE CHAIN REACTION Barbara K. Zehentner INTRODUCTION MATERIALS AND METHODS Tumor Cell Enrichment from Peripheral Blood RNA Extraction and cDNA Synthesis Multigene Real-Time RT-PCR RESULTS AND DISCUSSION REFERENCES 10. BREAST CANCER PATIENTS: DIAGNOSTIC EPIGENETIC MARKERS IN BLOOD Qinghua Feng and Nancy B. Kiviat INTRODUCTION USE OF DNA METHYLATION MARKERS IN CANCER DETECTION IDENTIFICATION OF DNA METHYLATION MARKERS CIRCULATING TUMOR DNA AS A DIAGNOSTIC TOOL FOR CANCER DETECTION METHODS FOR METHYLATION ANALYSIS BLOOD SAMPLE COLLECTION DNA ISOLATION FROM BLOOD BISULFITE CONVERSION Methylation Specific Polymerase Chain Reaction (MSP) Assay MethyLight Assay Nested Polymerase Chain Reaction Method POTENTIAL NOVEL METHODS DATA ANALYSIS EXAMPLES OF APPLICATIONS PERSPECTIVES AND LIMITATIONS REFERENCES 11. BREAST CANCER PATIENTS: DETECTION OF CIRCULATING CANCER CELL RELATED mRNA MARKERS BY MEMBRANE ARRAY METHOD Shiu-Ru Lin, Jaw-Yuan Wang, Ming-Yii Huang, and Chung-Chi Chen INTRODUCTION LIMITATION OF TRADITIONAL STANDARD METHOD FOR DETECTING THE CIRCULATING CANCER CELLS DETECTION OF mRNA-RELATED MOLECULES BY REVERSE TRANSCRIPTASE-PCR (RT-PCR) HISTOLOGICAL REVIEW OF DEVELOPING A POWER TOOL FOR DETECTING CIRCULATING CANCER CELLS WITH THE MEMBRANE ARRAY Membrane Array Preparation Preparation of Digoxigenin-labeled cDNA Targets and Hybridization Comparison of Membrane Array Method with Real-Time PCR Potential Clinical Application of Membrane Array Method FUTURE PERSPECTIVE REFERENCES 12. PREDICTION OF METASTASIS AND RECURRENCE OF BREAST CARCINOMA: DETECTION OF SURVIVIN- EXPRESSING CIRCULATING CANCER CELLS Shang-mian Yie INTRODUCTION DETECTION OF CIRCULATING BREAST CANCER CELLS Methods Used to Detect Circulating Cancer Cells Cytometric Methods Reverse Transcriptase-Polymerase Chain Reaction-Enzyme-Linked Immunosorbant Assay (RT-PCR-ELISA) Selection of Breast Cancer-Associated Marker Potential Clinical Applications REVERSE TRANSCRIPTION-POLYMERASE CHAIN REACTION-ELISA METHODOLOGY Preparation of RT-PCR-ELISA System Detection of Circulating Cancer Cells by RT-PCR-ELISA System Validation of RT-PCR-ELISA System CONCLUSIONS AND PERSPECTIVES REFERENCES 13. NODE-NEGATIVE BREAST CANCER: PREDICTIVE AND PROGNOSTIC VALUE OF PERIPHERAL BLOOD CYTOKERATIN-19 mRNA-POSITIVE CELLS Nikos Xenidis, Maria Perrakis, S. Kakolyris, Dimitris Mavroudis, and Vassilis Georgoulias INTRODUCTION PROGNOSTIC AND PREDICTIVE FACTORS Tumor Size Histological Grade Lymphatic and Vascular Invasion Proliferation Rate Estrogen and Progesterone Receptors Human Epidermal Growth Factor Receptor-2 (HER-2/neu) MINIMAL RESIDUAL DISEASE CIRCULATING TUMOR CELLS DETECTION OF CIRCULATING TUMOR CELLS Techniques for Circulating Tumor Cells Detection Preanalytical Circulating Tumor Cells Enrichment Techniques Cytometric Techniques Nucleic Acid-Based Techniques Molecular Markers for Circulating Tumor Cells Detection Markers with Low Breast Cancer Specificity Markers with High Breast Cancer Specificity CLINICAL RELEVANCE OF CIRCULATING TUMOR CELLS Predictive and Prognostic Value of Circulating Tumor Cells in Node- Negative Breast Cancer Patients REFERENCES 14. BREAST AND COLON CARCINOMAS: DETECTION WITH PLASMA CRIPTO-1 Caterina Bianco, Luigi Strizzi, Antonella De Luca, Nicola Normando, and David S. Salomon INTRODUCTION FUNCTION OF CRIPTO-1 DURING EMBRYONIC DEVELOPMENT CRIPTO-1 IN HUMAN MAMMARY GLAND DEVELOPMENT AND TUMORIGENESIS INTRACELLULAR SIGNALING PATHWAYS ACTIVATED BY CRIPTO-1 EXPRESSION OF CRIPTO-1 IN HUMAN COLON AND BREAST CARCINOMAS CRIPTO-1 AS TARGET FOR THERAPEUTIC INTERVENTION IN HUMAN CARCINOMAS DETECTION OF CRIPTO-1 IN THE PLASMA OF BREAST AND COLON CANCER PATIENTS WITH ENZYME-LINKED IMMUNOSORBENT ASSAY (ELISA)REFERENCES 15. BREAST CANCER RISK IN WOMEN WITH ABNORMAL CYTOLOGY IN NIPPLE ASPIRATE FLUID Kimberly Baltzell, Dixie Mills, Britt-Marie Ljung, Susan Love, and Margaret Wrensch INTRODUCTION CURRENT METHODS OF ASSESING BREAST CANCER RISK RISK ASSESSMENT MODELS BREAST DUCT ANATOMY Ductal Anatomy The Nipple NIPPLE ASPIRATE FLUID Collection of Nipple Aspirate Fluid Components of Nipple Aspirate Fluid CYTOLOGIC EVALUATION OF NIPPLE ASPIRATE FLUID RELATIONSHIP BETWEEN ABNORMAL CYTOLOGY IN NIPPLE ASPIRATE FLUID AND BREAST CANCER RISK REFERENCES 16. TISSUE MICROARRAYS: CONSTRUCTION AND UTILIZATION FOR BIOMARKER STUDIES Shannon M. Mumenthaler, Nam Yoon, Ai Li, Vei Mah, George Chang, Farzad Nooraie, Yahyah Elshimali, Stephanie Hanna, Sarang Kim, Steve Horvath, Sophia Apple, David Chia, David B. Seligson, and Lee Goodglick INTRODUCTION ADVANTAGES OF TISSUE MICROARRAY TECHNOLOGY CONSTRUCTION AND DEVELOPMENT OF A TISSUE MICROARRAY Donor Blocks and Core Size and Number Selecting the Right Tissue from the Correct Patient Population Available Tissue Microarrays TISSUE MICROARRAY SECTIONING LINKING TISSUE TO A PATIENT AND PATHOLOGY DATABASE PROTOCOL FOR MARKER ANALYSIS Sample Immunohistochemistry Protocol TISSUE MICROARRAYS PREPARED FROM FROZEN TISSUE QUANTIFYING BIOMARKER EXPRESSION Manual Scoring Automated Scoring DATA ANALYSIS: SPOT LEVEL AND POOLED DATA Spot-level Analysis Pooled Data STATISTICAL TOOLS DISEASE PROGRESSION STUDY Annexin A1 Study GATA-3 Study MULTIMARKER STUDY CONCLUSION REFERENCES 17. SYSTEMATIC VALIDATION OF BREAST CANCER BIOMARKERS USING TISSUE MICROARRAYS: FROM CONSTRUCTION TO IMAGE ANALYSIS Catherine M.A. Kelly, Denise Ryan, Sarah Penny, and William M. Gallagher INTRODUCTION DEFINITION OF A BIOMARKER CANDIDATE BIOMARKER IDENTIFICATION USING DNA MICROARRAYS SYTEMATIC APPROACH TO BIOMARKER IDENTIFICATION AND VALIDATION TISSUE MICROARRAYS CELL PELLET ARRAYS FROZEN TUMOR TISSUE MICROARRAY FROZEN PROTEIN ARRAY TISSUE IMMUNOBLOTTING TISSUE MICROARRAY ASSAY WESTERN BLOT ANALYSIS AND ANTIBODY OPTIMIZATION WESTERN BLOTTING IMMUNOHISTOCHEMISTRY MANUAL ANALYSIS DIGITAL SLIDE SCANNING IMAGE STORAGE DIGITAL SLIDE SCANNING AND STORAGE REFERENCES 18. PHYLLODES TUMORS OF THE BREAST: ROLE OF IMMUNOHISTOCHEMISTRY IN DIAGNOSIS Puay Hoon Tan, Gary Man-Kit Tse, George Wai-Cheong Yip, and Boon Huat Bay INTRODUCTION CLINICOPATHOLOGICAL FEATURES OF PHYLLODE TUMORS IMMUNOHISTOCHEMISTRY ROLE OF IMMUNOHISTOCHEMISTRY IN DIFFERENTIAL DIAGNOSIS OF PHYLLODE TUMORS ROLE OF IMMUNOHISTOCHEMISTRY IN PROGNOSIS OF PHYLLODE TUMORS ROLE OF IMMUNOHISTOCHEMISTRY IN UNDERSTANDING THE PATHOGENESIS OF PHYLLODE TUMORS REFERENCES 19. PHYLLODES TUMOR OF THE BREAST: PROGNOSIS ASSESSMENT USING IMMUNOHISTOCHEMISTRY Nicole Nicosia Esposito and David J. Dabbs INTRODUCTION IMMUNOHISTOCHEMICAL ANALYSIS Marker of Proliferation: Ki-67 (MIB-1) Tumor Suppressor Gene P53 Steroid Receptors: Estrogen and Progesterone Receptors Proteins with Targeted Therapy Implications C-kit (CD117) Epidermal Growth Factor Receptor HER-2/neu CHROMOSOMAL AND MOLECULAR ANALYSIS HISTOPATHOLOGIC ANALYSIS REFERENCES 20. METAPLASTIC BREAST CARCINOMA: DETECTION USING HISTOLOGY AND IMMUNOHISTOCHEMISTRY Tibor Tot INTRODUCTION DEFINITION CURRENT CLASSIFICATION HISTOLOGY IMMUNOHISTOCHEMISTRY THE CONCEPT OF BASAL-LIKE TUMORS CLINICOPATHOLOGICAL FEATURES PROGNOSTIC AND PREDICTIVE PARAMETERS REFERENCES 21. INVASIVE BREAST CANCER: OVEREXPRESSION OF HER-2 DETERMINED BY IMMUNOHISTOCHEMISTRY AND MULTIPLEX LIGAND-DEPENDENT PROBE AMPLIFICATION Paul J. van Diest, C.B. Moelans, D. Purnomosari, G. Pals, and R.A. de Weger INTRODUCTION MULTIPLEX LIGATION-DEPENDENT PROBE AMPLIFICATION OF HER-2/neu AMPLIFICATION CORRELATION BETWEEN HER-2/neu MULTIPLEX LIGATION- DEPENDENT PROBE AMPLIFICATION AND IMMUNOHISTOCHEMISTRY DISCUSSION REFERENCES 22. OPERABLE BREAST CANCER: NEOADJUVANT TREATMENT (METHODOLOGY) Manfred Kaufmann, Sibylle Loibl, and Gunter von Minckwitz INTRODUCTION DIAGNOSIS TREATMENT DECISION Chemotherapy Endocrine Therapy Therapy for HER-2/neu-Overexpressing Tumors Predictive Marker of Response and Resistance LOCAL TREATMENT Surgical Management of the Breast Surgical Management of the Axilla Radiotherapy PATHOLOGY REFERENCES 23. CHEMOTHERAPY FOR BREAST CANCER James A. McCubrey, Richard A. Franklin, Partick M. Navolanic, Alberto M. Martelli, and Linda S. Steelman INTRODUCTION METHOTREXATE AND 5-FLUOROURACIL CYCLOPHOSPHAMIDE ANTHRACYCLINES TAXANES TRASTUZUMAB TAMOXIFEN AROMATASE INHIBITORS REFERENCES 24. LOCALLY ADVANCED BREAST CANCER: ROLE OF CHEMOTHERAPY IN IMPROVING PROGNOSIS Giuseppe Frasci, Giuseppe D'Aiuto, Giovanni Iodice, Massimiliano D'Aiuto, and Giuseppe Comella INTRODUCTION Preoperative Versus Postoperative Chemotherapy CLINICOPATHOLOGICAL END POINTS AND LONG-TERM OUTCOME SEARCHING FOR THE BEST NEOADJUVANT TREATMENT Drugs Dose and Schedule ROLE OF TAREGETED THERAPY Trastuzumab Lapatinib Bevacizumab Other Molecules CORRECT INDIVIDUALIZATION OF THE TREATMENT Hormone Receptor Status Gene Expression Profile Early Assessment of Tumor Response TAILORED NEOADJUVANT CHEMOTHERAPY MAY IMPROVE THE PROGNOSIS CONCLUSIONS REFERENCES 25. THE RELEVANCE OF DOSE-INTENSITY FOR ADJUVANT TREATMENT OF BREAST CANCER Sherko Kummel, Mahdi Rezai, Rainer Kimmig, and Peter Schmid INTRODUCTION DOSE-INTENSITY AND DOSE-DENSITY THEORETICAL FRAMEWORK CANCER AND LEUKEMIA GROUP B TRIAL 9741 AND GRUPPO ONCOLOGIA GONO-MIC STUDY ECOG 1199 STUDY Evidence from other Adjuvant Trials Evidence from Neoadjuvant Trials REFERENCES 26. ADVANCED BREAST CANCER: TREATMENT WITH DOCETAXEL/EPIRUBICIN A.G. Pallis, V. Georgoulias, and D. Mavroudis INTRODUCTION Epirubicin Docetaxel Anthracycline-Taxane combination DOCETAXEL-EPIRUBICIN COMBINATION Phase 1 Studies Toxicity of the Docetaxel-Epirubicin Combination Pharmacokinetic Data PHASE II STUDIES OF THE DOCETAXEL/EPIRUBICIN COMBINATION REFERENCES 27. SYSTEMIC THERAPY FOR BREAST CANCER: USING TOXICITY DATA TO INFORM DECISIONS John K. Erban and Joseph Lau INTRODUCTION CATEGORIES OF SYSTEMIC THERAPY FOR BREAST CANCER Hormonal Therapy Chemotherapy Biological and Targeted Therapeutics Supportive Agents as Anticancer Therapy MEASURING HARMS OF SYSTEMIC THERAPY RISKS OF ACUTE TOXICITIES LATER SEQUELAE OF SYSTEMIC THERAPY AND CHOICE OF TREATMENT HARMS RELATED TO EFFECTIVE TREATMENT MODALITIES Cardiac and Cardiovascular Toxicity Neurological Effects of Therapy Musculoskeletal Complications Secondary Malignancy Fertility, Teratogenicity, and in utero Effects on the Fetus CONCLUSIONS AND RECOMMENDATIONSREFERENCES 28. CHEMOTHERAPY FOR METASTATIC BREAST CANCER: PATIENTS WHO RECEIVED ADJUVANT ANTHRACYCLINES (AN OVERVIEW) Alessandro Morabito, Maria Carmela Piccirillo, Jane Bryce, Katia Monaco, Gianfranco De Feo, Antonia Del Giudice, Fabiano Falasconi, and Francesco Perrone INTRODUCTION FIRST-LINE ANTHRACYCLINE-CONTAINING REGIMENS CURRENT OPTIONS OF TREATMENT FOR HER-2-NEGATIVE METASTATIC BREAST CANCER PATIENTS Taxanes as Single Agents or in Combination with Non-Cross-Resistant Drugs Combinations without Anthracyclines and Taxanes Combinations with Liposomal Anthracyclines CURRENT OPTIONS OF TREATMENT FOR HER-2 POSITIVE METASTATIC BREAST CANCER PATIENTS Trastuzumab and Anthracyclines Trastuzumab and Taxanes Trastuzumab Combinations Without Anthracyclines and/or Taxanes Trastuzumab and Polychemotherapy Trastuzumab and Liposomal Anthracyclines CONCLUSIONS AND FUTURE PERSPECTIVES REFERENCES 29. ESTROGEN RECEPTOR-NEGATIVE AND HER-2/neu- POSITIVE LOCALLY ADVANCED BREAST CARCINOMA: THERAPY WITH PACLIAXEL AND GRANULOCYTE-COLONY STIMULATING FACTOR Giuseppe Frasci, Giuseppe D'Aiuto, Giovanni Iodice, Renato Thomas, Massimiliano D'Aiuto, and Giuseppe Comella HORMONE RECEPTOR STATUS AND RESPONSE TO CHEMOTHERAPY HER-2/neu STATUS AND RESPONSE TO CHEMOTHERAPY PACLIAXEL- CHEMOTHERAPY AS PRIMARY TREATMENT OF LARGE OPERABLE OR LOCALLY ADVANCED BREAST CANCER WEEKLY CISPLATIN-EPIRUBICIN-PACLITAXEL WITH G-CSF SUPPORT IN LABC WEEKLY CISPLATIN-EPIRUBICIN-PACLITAXEL WITH G-CSF SUPPORT IN LARGE OPERABLE DISEASE DISCUSSION REFERENCES 30. BREAST CANCER: SIDE EFFECTS OF TAMOXIFEN AND ANASTROZOLE John R. Benson, E.H. Turner, and Zoe Winters INTRODUCTION BIOLOGICAL MODELS ANTIHORMONAL THERAPIES Antiestrogens Aromatose Inhibitors ADVANCED BREAST CANCER NEOADJUVANT HORMONAL THERAPY ADJUVANT HORMONAL THERAPY ADJUVANT TRIALS OF TAMOXIFEN ADJUVANT TRIALS OF AROMATOSE INHIBITORS CHEMOPREVENTION Tamoxifen Aromatose Inhibitors SIDE-EFFECTS OF HORMONAL THERAPIES Tamoxifen AROMATOSE INHIBITORS SIDE-EFFECTS OF HORMONAL TREATMENT CONCLUSIONS REFERENCES 31. BREAST CANCER: EXPRESSION OF HER-2 AND EPIDERMAL GROWTH FACTOR RECEPTOR AS CLINICAL MARKERS FOR RESPONSE TO TARGETED THERAPY Stanley E. Shackney, David R. Emlet, Russell Schwartz, Kathryn A. Brown, Agnese A. Pollice, and Charles A. Smith INTRODUCTION CELL AND MOLECULAR BIOLOGY OF HER-2/EPIDERMAL GROWTH FACTOR RECEPTOR INTERACTIONS QUANTITATIVE CONSIDERATIONS DYNAMIC ASPECTS OF HER-2 AND EPIDERMAL GROWTH FACTOR RECEPTOR SIGNALING TECHNICAL ASPECTS OF CLINICAL MEASUREMENTS OF HER-2 AND EPIDERMAL GROWTH FACTOR RECEPTOR TECHNICAL ASPECTS OF CLINICAL MEASUREMENTS OF HER-2 AND EPIDERMAL GROWTH FACTOR RECEPTOR: IMMUNOHISTOCHEMISTRY VERSUS IMMUNOFLUORESCENCE TECHNICAL ASPECTS OF CLINICAL MEASUREMENTS OF HER-2 AND EPIDERMAL GROWTH FACTOR RECEPTOR: FLUORESCENCE IN SITU HYBRIDIZATION EXPRESSION OF HER-2 AND EPIDERMAL GROWTH FACTOR RECEPTOR OVERVIEW AND CONCLUSIONS REFERENCES 32. YOUNG BREAST CANCER PATIENTS UNDERGOING BREAST-CONSERVING THERAPY: ROLE OF BRCA1 AND BRCA2 Andrea Chao Bafford, Judy E. Garber, Anu Chittenden, and Mehra Golshan INTRODUCTION BRCA1 AND BRCA2 BRCA-RELATED BREAST CANCER BREAST-CONSERVING THERAPY VERSUS MASTECTOMY BREAST-CONSERVING THERAPY IN BRCA CARRIERS ALGORITHM FOR SURGICAL DECISION MAKING REFERENCES 33. RADIATION THERAPY FOR OLDER WOMEN WITH EARLY BREAST CANCER Benjamin D. Smith INTRODUCTION EPIDEMIOLOGY NATURAL HISTORY PATHOLOGY RADIATION THERAPY FOR LOCAL CONTROL RADIATION THERAPY FOR REGIONAL CONTROL RADIATION THERAPY TO IMPROVE SURVIVAL RADIATION TECHNIQUES RADIATION TOXICITY REFERENCES 34. ACUTE SIDE EFFECTS OF RADIOTHERAPY IN BREAST CANCER PATIENTS: ROLE OF DNA-REPAIR AND CELL CYCLE CONTROL GENES Xiang-Lin Tan, Odilia Popanda, and Jenny Chang-Claude INTRODUCTION Selection of Possible Marker Genes and Single Nucleotide Polymorphisms DNA Repair Genes and Clinical Radiation Reaction Cell Cycle Control Genes TP53 and p21, Clinical Radiation Reaction MATERIALS AND METHODS Study Subjects and Data Collection Genotyping Methods Statistical Methods RESULTS Gentotype-Specific Risks to Acute Skin Toxicity of Radiotherapy Haplotype-Specific Risks to Acute Skin Toxicity of Radiotherapy Combined Effects of Genotypes on the Risk of Acute Skin Toxicity after Radiotherapy Joint Effects of the Genotypes in DNA Repair Genes and TP53 Arg72 Pro DISCUSSION Polymorphisms in DNA Repair Genes and the Risk of Acute Side Effects after Radiotherapy Polymorphisms in TP53 and p21 Genes and the Risk of Acute Side Effects after Radiotherapy Joint Effects of the Polymorphisms in DNA Repair Genes and TP53 Body Mass Index and Development of Acute Side Effects after Radiotherapy Epidemiological and Clinical Characteristics, Strengths, and Limitations of the Study REFERENCES 35. 18F-FLUORODEOXYGLUCOSE/POSITRON EMISSION TOMOGRAPH IN PRIMARY BREAST CANCER: FACTORS RESPONSIBLE FOR FALSE-NEGATIVE RESULTS Rakesh Kumar and Neena Lal INTRODUCTION TUMOR SIZE HISTOLOGICAL TUMOR TYPE TUMOR GRADE PATTERNS Proliferative Activity Tumor Blood Vessel Density TISSUE HETEROGENICITY UNIFOCAL VERSUS MULTIFOCAL BREAST LESIONS ESTROGEN AND PROGESTERONE RECEPTORS BREAST DENSITY AXILLARY LYMPH NODE SPREAD Distant Spread BLOOD GLUCOSE LEVELS GLUCOSE TRANSPORTERS DATA ACQUISITION AND DATA ANALYSIS RECENT DEVELOPMENTS REFERENCES 36. SENTINEL LYMPH NODE SURGERY DURING PROPHYLACTIC MASTECTOMY (METHODOLOGY) Judy C. Boughey and Isabelle Bedrosian INTRODUCTION PREOPERATIVE EVALUATION PRIOR TO SENTINEL LYMPH NODE SURGERY AND PROPHYLACTIC MASTECTOMY METHODOLOGY OF SENTINEL LYMPH NODE SURGERY AT THE TIME OF PROPHYLACTIC MASTECTOMY Choice of Mapping Agent Site of Injection of Mapping Agent Time of Injection of Mapping Agent Lymphoscintigraphy Surgical Technique Pathological Analysis of Sentinel Lymph Node INDICATORS FOR PERFORMING SENTINEL LYMPH NODE SURGERY AT THE TIME OF PROPHYLACTIC MASTECTOMY REFERENCES 37. BREAST CONSERVATION SURGERY: METHODS Lloyd A. Mack, Robert L. Lindsay, and Walley J. Temple INTRODUCTION SURGICAL METHODS Skin Incisions Tumor Removal Closure of Defect/Skin Closure Oncoplastics Minimally Invasive/Ablative Techniques REFERENCES 38. LYMPH NODE-NEGATIVE BREAST CARCINOMA: ASSESSMENT OF HER-2/neu GENE STATUS AS PROGNOSTIC VALUE Gloria Peiro INTRODUCTION PROTEIN OVEREXPRESSION Enzyme-Linked Immunosorbent Assay Immunohistochemistry mRNA OVEREXPRESSION Quantitative Real-Time Reverse Transcription-Polymerase Chain Reaction cDNA Microarray-Based Method GENE AMPLIFICATION Southern and Slot Blotting Fluorescence In Situ Hybridization Bright-field In Situ Hybridization Chromogenic In Situ Hybridization Silver-Enhanced In Situ Hybridization Quantitative Real-Time Reverse Transcription-Polymerase Chain Reaction REFERENCES 39. MULTIFOCAL OR MULTICENTRIC BREAST CANCER: UNDERSTANDING ITS IMPACT ON MANAGEMENT AND TREATMENT OUTCOMES Julia L. Oh DEFINITIONS OF MULTIFOCALITY AND MULTICENTRICITY IMPACT ON SURGICAL RESECTION IMPACT ON ADJUVANT RADIATION THERAPY NEOADJUVANT CHEMOTHERAPY AND LOCOREGIONAL THERAPY CONCLUSIONS ON MANAGEMENT REFERENCES 40. ARE BREAST CANCER SURVIVORS AT RISK OF DEVELOPING OTHER CANCERS? Jaime S. Raymond and Carol J. Rowland Hogue SUMMARY INTRODUCTION MATERIALS AND METHODS Population Definition of Second Primary Tumors Analysis of Risk of Second Primary Tumors RESULTS DISCUSSION REFERENCES 41. DISTANT METASTASIS IN ELDERLY PATIENTS WITH BREAST CANCER: PROGNOSIS WITH NODAL STATUS Anees B. Chagpar INTRODUCTION BREAST CANCER IN THE ELDERLY Tumor Biology Patient Comorbidities DETERMINANTS OF DISTANT METASTATIC DISEASE LYMPH NODE EVALUATION IN THE ELDERLY REFERENCES 42. CONCOMITANT USE OF TAMOXIFEN WITH RADIOTHERAPY ENHANCES SUBCUTANEOUS BREAST FIBROSIS IN HYPERSENSITIVE PATIENTS David Azria, Yazid Belkacemi, Joseph Gligorov, and M. Ozsahin BACKGROUND CONCURRENT TAMOXIFEN AND RADIOTHERAPY Preclinical Data Clinical Results Efficacy of Combined TAM-RT Treatment Toxicitites Combined TAM-RT Treatment TAMOXIFEN AND RADIOTHERAPY IN HYPERSENSITIVE PATIENTS Methodology Radiation-induced Apoptosis Treatment Modalities Radiation-induced Assessment of Side Effects Statistical Analysis RESULTS Patient Characteristics Treatment Delivery Acute Toxicity Relapse-free and Overall Survival Late Side Effects Complication-relapse-free Survival Complication-free Survival DISCUSSION AND PERSPECTIVES REFERENCES 43. MALIGNANT PHYLLODES TUMOR OF THE BREAST: IS ADJUVANT RADIOTHERAPY NECESSARY? Aaron P. Brown, David K. Gaffney, and O. Kenneth Macdonald INTRODUCTION CLINICAL PRESENTATION AND DIAGNOSIS Patient Characteristics Triple Assessment Clinical Examination Radiological Imaging Histological Analysis PROGNOSIS TREATMENT Surgery Surgical Technique Radiotherapy Radiation Technique Chemotherapy Chemotherapy Technique SUMMARY REFERENCES 44. LOCALLY ADVANCED BREAST CANCER: MULTIDRUG RESISTANCE Can Atalay INTRODUCTION LOCALLY ADVANCED BREAST CANCER MULTIDRUG RESISTANCE ABCB1 (MDR1) Protein ABCC1 (MRP1) Protein ABCG2 (BCRP) Protein MULTIDRUG RESISTANCE IN LOCALLY ADVANCED BREAST CANCER Effects of MDR on Clinical Response to Chemotherapy Effects of MDR on Survival MODULATION OF ABC TRANSPORTERS FUTURE PERSPECTIVES REFERENCES 45. BREAST CANCER: DIAGNOSIS OF RECURRENCE USING 18F-FLUORODEOXYGLUCOSE-POSITRON EMISSION TOMOGRAPHY/COMPUTED TOMOGRAPHY Simona Ben-Haim and Lea Radan INTRODUCTION METHODOLOGY: FDG-PET AND PET/CT IMAGING Image Interpretation FDG-PET AND PET/CT IMAGING FOR BREAST CANCER RECURRENCE REFERENCES 46. ROLE OF SENTINEL LYMPH NODE BIOPSY IN DUCTAL CARCINOMA IN SITU: DIAGNOSIS AND METHODOLOGY Amit Goyal INTRODUCTION PATIENT SELECTION METHODOLOGY: SENTINEL LYMPH NODE BIOPSY Choice of Radioisotope Dose of Radioisotope Timing of Injection Lymphoscintigraphy Operative Technique REFERENCES 47. BREAST CONSERVATION TREATMENT OF EARLY STAGE BREAST CARCINOMA: RISK OF CARDIAC MORTALITY Eleanor E.R. Harris INTRODUCTION CARDIAC MORTALITY IMAGING STUDIES ASSESSING CARDIAC INJURY TECHNIQUES FOR REDUCING CARDIAC TOXICITY Daily Positioning Intensity Modulated Radiation Therapy Breath Hold Techniques REFERENCES