Methods of Cancer Diagnosis, Therapy and Prognosis: Breast Carcinoma

Contents......Page 19
Authors and Co-Authors of Volume 1......Page 6
Preface......Page 16
Contents of Volume 2......Page 43
1. Breast Cancer: An Introduction......Page 46
Reference......Page 48
Introduction......Page 49
Development of Computer-Aided Detection Schemes......Page 50
Evaluation of Computer-Aided Detection Scheme Performance......Page 53
Performance of Computer-Aided Detection Schemes on Spiculated Masses with Dense Background......Page 55
Performance of Computer-Aided Detection Schemes on False-Negative Cases and Prior Images......Page 54
Performance of Computer-Aided Detection Schemes in Detecting Lesions with Architectural Distortion......Page 56
Reproducibility of Results of Computer-Aided Detection Schemes......Page 57
Application of Computer-Aided Detection Schemes to Clinical Environment......Page 58
Rejection of Computer-Aided Detection Scheme Prompted False-Negative Masses in Screening Environment......Page 59
Improvement of Detecting Cancers Associated with Micro-Calcification Clusters......Page 60
Optimal Assessment of Computer-Aided Detection Effect on Radiologists\' Performance......Page 61
Change of Cancer Detection and Recall Rates Before and After Introduction of Computer-Aided Detection Systems......Page 62
Multi-View Based Computer-Aided Detection Schemes......Page 63
Computer-Aided Detection Schemes with Interval Change Classifiers......Page 65
Interactive Computer-Aided Detection and Visual Aid......Page 67
References......Page 69
Methods......Page 72
Pathologic Findings......Page 73
Differential Diagnosis......Page 74
References......Page 75
Angiogenesis......Page 76
Integrins......Page 77
Scintimammography......Page 78
Technetium Labeled NC100692......Page 79
Gamma Cameras and Imaging Protocols......Page 80
Results and Efficacy......Page 81
Improvements in Gamma Camera Technology......Page 82
Future of Integrin Scintigraphy......Page 83
References......Page 84
MicroRNA Biogenesis......Page 86
Biological Roles of MicroRNAs......Page 87
Isolation Methods......Page 88
Procedure for miRNA Isolation from Prostate and Breast Tumor Biopsies......Page 89
Amplification of Low Molecular Weight RNA......Page 90
First Strand cDNA Synthesis......Page 91
Tailing of First Strand cDNA......Page 93
Labeling of miRNA......Page 94
Enrichment and Concentration of LMW RNA Using YM-100 and YM-3 Columns......Page 95
Poly (A) Tailing......Page 96
Array Hybridization......Page 97
Detection Platforms for MicroRNA Profiling......Page 98
Analysis of MicroRNA Expression Data......Page 99
References......Page 100
Introduction......Page 103
Materials......Page 105
Methods......Page 107
Atypical Lobular Hyperplasia (ALH)......Page 108
Ductal Carcinoma in situ (DCIS)......Page 109
Results and Discussion......Page 110
References......Page 112
Radiological Appearance of Papillary Lesions of the Breasts......Page 114
Pathological Findings......Page 116
Association of Papillary Lesions with Ductal Carcinoma......Page 117
Fine Needle Aspiration......Page 118
Core Needle Biopsy......Page 119
Current Role of Excisional Biopsy......Page 120
Technique of Stereotactic Vacuum-Assisted Biopsy......Page 121
Vacuum-Assisted Biopsy......Page 22
Technique of Ultrasound-Guided Vacuum-Assisted Biopsy......Page 122
Advantages of Directional Vacuum-Assisted Device......Page 123
Complications of Vacuum-Assisted Biopsy......Page 125
Current Experience of Vacuum-Assisted Biopsy and Percutaneous Core Biopsy in the Management of Papillary Lesions......Page 126
Is Excision Biopsy Needed in Assessing Papillary Lesions of the Breast?......Page 129
Atypical Papilloma/Papillary Lesion with Atypical Ductal Hyperplasia at Vacuum-Assisted Biopsy......Page 132
Benign Papilloma at Vacuum-Assisted Biopsy......Page 133
References......Page 136
Introduction......Page 139
Technique of Sentinel Node Biopsy in Multicentric Breast Cancer......Page 140
Technique of Lymphatic Mapping......Page 141
Results of the Austrian Sentinel Node Study Group......Page 142
Patients and Data......Page 143
Follow-Up......Page 144
Discussion......Page 145
Qualitiy Control of Sentinel Node Biopsy Procedure......Page 146
References......Page 147
Serum Tumor Markers and Breast Cancer......Page 149
Carcinoembryonic Antigen......Page 150
Prediction of Risk of Recurrent and Locoregional Relapse......Page 151
Monitoring the Response to Therapy of Recurrences......Page 152
Conclusions......Page 153
References......Page 154
Introduction......Page 156
Multigene Real-Time RT-PCR......Page 157
Results and Discussion......Page 158
References......Page 161
Introduction......Page 163
Identification of DNA Methylation Markers......Page 164
Circulating Tumor DNA as a Diagnostic Tool for Cancer Detection......Page 165
Blood Sample Collection......Page 166
DNA Isolation from Blood......Page 167
Materials and Regents......Page 168
Procedure......Page 169
Methylation Specifi c PCR (MSP) Assay......Page 170
Methylight Assay......Page 171
Nested Polymerase Chain Reaction Method......Page 172
Data Analysis......Page 173
Examples of Applications......Page 174
Perspectives and Limitations......Page 175
References......Page 176
Limitation of Traditional Standard Method for Detecting the Circulating Cancer Cells......Page 179
Detection of mRNA-Related Molecules by Reverse-Transcriptase PCR (RT-PCR)......Page 180
Histological Review of Developing a Power Tool for Detecting Circulating Cancer Cells with the Membrane Array......Page 181
Membrane Array Preparation......Page 182
Preparation of Digoxigenin-Labeled cDNA Targets and Hybridization......Page 183
Comparison of Membrane Array Method with Real-Time PCR......Page 184
Potential Clinical Application of Membrane Array Method......Page 185
Future Perspective......Page 189
References......Page 191
Introduction......Page 194
Cytometric Methods......Page 195
Reverse Transcription-Polymerase Chain Reaction (RT-PCR) Technique......Page 196
Potential Clinical Significance......Page 197
Reverse Transcription-Polymerase Chain Reaction-Enzyme- Linked Immunosorbant Assay (RT-PCR-ELISA)......Page 198
Selection of Breast Cancer-Associated Marker......Page 199
Potential Clinical Applications......Page 201
First-Round PCR......Page 203
Preparation of Nuclear Hybridization Platform......Page 204
Quantitative Determination of PCR Products by Nuclear Hybridization-Based ELISA......Page 205
Validation of ELISA Process......Page 206
Conclusions and Perspectives......Page 208
References......Page 209
Prognostic and Predictive Factors......Page 212
Proliferation Rate......Page 214
Minimal Residual Disease......Page 216
Detection of Circulating Tumor Cells......Page 217
Techniques for Detecting Circulating Tumor Cells......Page 218
Molecular Markers for Detecting Circulating Tumor Cells......Page 220
Predictive and Prognostic Value of Circulating Tumor Cells in Node-Negative Breast Cancer Patients......Page 221
Conclusion......Page 222
References......Page 223
Introduction......Page 226
Cripto-1 in Human Mammary Gland Development and Tumorigenesis......Page 227
Intracellular Signaling Pathways Activated by Cripto-1......Page 229
Expression of Cripto-1 in Human Colon and Breast Carcinomas......Page 230
Cripto-1 as Target for Therapeutic Intervention in Human Carcinomas......Page 232
Detection of Cripto-1 in the Plasma of Breast and Colon Cancer Patients with Enzyme-Linked Immunosorbent Assay (ELISA)......Page 234
References......Page 237
Introduction......Page 240
Risk Assessment Models......Page 241
Ductal Anatomy......Page 244
The Nipple......Page 245
Collection of Nipple Aspirate Fluid......Page 246
Cytologic Evaluation of Nipple Aspirate Fluid......Page 247
The Relationship Between Abnormal Cytology in Nipple Aspirate Fluid and Breast Cancer Risk......Page 249
References......Page 250
Introduction......Page 254
Construction and Development of a Tissue Microarray......Page 255
Linking Tissue to a Patient and Pathology Database......Page 258
Protocol for Marker Analysis......Page 259
Sample Immunohistochemistry Protocol......Page 260
Quantifying Biomarker Expression......Page 261
Data Analyses: Spot Level and Pooled Data......Page 263
Statistical Tools......Page 264
Disease Progression Study......Page 267
References......Page 269
Validated Biomarkers......Page 272
Definition of a Biomarker......Page 273
Candidate Biomarker Identifi cation Using DNA Microarrays......Page 274
Candidate Identification......Page 275
Tissue Microarrays......Page 277
Designing the Tissue Microarray......Page 278
Sectioning the Array Block......Page 279
Constructing a Cell Pellet......Page 280
Tissue Microarray Assay......Page 281
Western Blotting......Page 282
Immunohistochemistry......Page 283
Digital Slide Scanning......Page 284
Conclusion......Page 285
References......Page 286
Introduction......Page 288
Immunohistochemistry......Page 289
Proliferation Indices......Page 290
p53......Page 291
c-kit (CD117)......Page 292
CD10......Page 293
Heparan sulfate......Page 294
Vascular endothelial growth factor......Page 295
Role of Immunohistochemistry in Understanding the Pathogenesis of Phyllodes Tumors......Page 296
References......Page 297
Introduction......Page 300
Tumor-Suppressor Gene: P53......Page 302
C-KIT (CD117)......Page 303
Epidermal Growth Factor Receptor......Page 304
Histopathologic Analysis as a Predictor of Prognosis in Phyllodes Tumors......Page 305
Conclusion......Page 307
References......Page 308
Definition......Page 311
Histology......Page 313
Immunohistochemistry......Page 317
The Concept of Basal–Like Tumors......Page 320
Clinicopathological Features......Page 321
Prognostic and Predictive Parameters......Page 324
References......Page 325
Introduction......Page 327
Multiplex Ligation-Dependent Probe Amplification......Page 328
Multiplex Ligation-Dependent Probe Amplification for Detection of HER-2/neu Amplification......Page 329
Correlations Between HER-2/neu Multiplex Ligation-Dependent Probe Amplification and Immunohistochemistry......Page 330
Correlation Between Multiplex Ligation-dependent Probe Amplification and Other Amplification Detection Methods......Page 331
Discussion......Page 335
References......Page 337
Diagnosis......Page 341
Treatment Decision......Page 342
Chemotherapy......Page 343
Endocrine Therapy......Page 344
Predictive Marker of Response and Resistance......Page 346
Surgical Management of the Breast......Page 347
Radiotherapy......Page 348
Pathology......Page 349
References......Page 350
Methotrexate and 5-Fluorouracil......Page 355
Taxanes......Page 356
Tamoxifen......Page 357
References......Page 358
Introduction......Page 362
Preoperative Versus Postoperative Chemotherapy......Page 363
Clinicopathological End Points and Long-Term Outcome......Page 364
Drugs......Page 365
Dose and Schedule?......Page 368
Trastuzumab......Page 371
Lapatinib......Page 372
Other Molecules......Page 373
Gene Expression Profi le......Page 374
Early Assessment of Tumor Response......Page 375
Tailored Neoadjuvant Chemotherapy may Improve the Prognosis......Page 376
Conclusions......Page 379
References......Page 380
Dose Intensity and Dose Density – Theoretical Framework......Page 385
Cancer and Leukemia Group B Trial 9741 and Gruppo Oncologica GONO-MIG Study......Page 387
ECOG 9911 Study......Page 388
Evidence from Other Adjuvant Trials......Page 389
Evidence from Neoadjuvant Trials......Page 391
References......Page 392
Docetaxel......Page 395
Anthracycline-Taxane Combination......Page 396
Phase I Studies......Page 397
Toxicity of the Docetaxel-Epirubicin Combination......Page 398
Phase II Studies of the Docetaxel/Epirubicin Combination......Page 399
References......Page 403
Introduction......Page 406
Hormonal Therapy......Page 407
Chemotherapy......Page 408
Biological and Targeted Therapeutics......Page 409
Supportive Agents as Anticancer Therapy......Page 410
Measuring Harms of Systemic Therapy......Page 411
Risks of Acute Toxicities......Page 414
Later Sequelae of Systemic Therapy and Choice of Treatment......Page 415
Cardiac and Cardiovascular Toxicity......Page 417
Neurological Effects of Therapy......Page 420
Musculoskeletal Complications......Page 421
Secondary Malignancy......Page 422
Conclusions and Recommendations......Page 423
References......Page 424
Introduction......Page 428
First-Line Anthracycline-Containing Regimens......Page 429
Taxanes as Single Agents or in Combination with Non-Cross- Resistant Drugs......Page 431
Combinations without Anthracyclines and Taxanes......Page 434
Combinations with Liposomal Anthracyclines......Page 435
Trastuzumab and Anthracyclines......Page 436
Trastuzumab and Taxanes......Page 437
Trastuzumab Combinations without Anthracyclines and/or Taxanes......Page 439
Trastuzumab and Polychemotherapy......Page 440
Conclusions and Future Perspectives......Page 441
References......Page 443
Hormone Receptor Status and Response to Chemotherapy......Page 448
Weekly Cisplatin-Epirubicin-Paclitaxel with G-CSF Support in Locally Advanced Breast Cancer......Page 453
Dose Adjustments According to Toxicity......Page 454
Results......Page 455
Weekly Cisplatin-Epirubicin-Paclitaxel with G-CSF Support in Large Operable Disease......Page 456
Results......Page 457
Discussion......Page 459
References......Page 463
Introduction......Page 466
Biological Models......Page 467
Anti-Hormonal Therapies......Page 469
Advanced Breast Cancer......Page 471
Neoadjuvant Hormonal Therapy......Page 472
Adjuvant Trials of Tamoxifen......Page 473
Adjuvant Trials of Aromatase Inhibitors......Page 474
Tamoxifen......Page 477
Aromatase Inhibitors......Page 479
Tamoxifen......Page 480
Aromatase Inhibitors......Page 482
Patient Information......Page 484
Conclusions......Page 485
References......Page 486
Cell and Molecular Biology of HER-2/Epidermal Growth Factor Receptor Interactions......Page 491
Quantitative Considerations......Page 492
Transient Effects Involving HER-2/EGFR Signaling......Page 495
Evolution of HER-2+ Tumors......Page 497
Technical Aspects of Clinical Measurements of HER-2 and Epidermal Growth Factor Receptor......Page 501
Technical Aspects of Clinical Measurements of HER-2 and Epidermal Growth Factor Receptor: Immunohistochemistry......Page 502
Epidermal Growth Factor Receptor: Fluorescence In Situ Hybridization......Page 503
Survey of Fluoresence In Situ Hybridization Patterns in Single Cell Suspensions......Page 504
Expression of HER-2 and Epidermal Growth Factor Receptor......Page 505
Overview and Conclusions......Page 509
References......Page 512
BRCA1 and BRCA2......Page 515
BRCA Related Breast Cancer......Page 516
Breast-Conserving Therapy Versus Mastectomy......Page 517
Algorithm: For Surgical Decision Making......Page 519
References......Page 520
Introduction......Page 524
Natural History......Page 525
Radiation Therapy for Local Control......Page 526
Radiation Therapy for Regional Control......Page 530
Radiation Therapy to Improve Survival......Page 532
Radiation Techniques......Page 533
References......Page 535
Selection of Possible Marker Genes and SNPs......Page 538
DNA Repair Genes and Clinical Radiation Reaction......Page 539
Cell Cycle Control Genes TP53 and p21, and Clinical Radiation Reaction......Page 541
Study Subjects and Data Collection......Page 542
Genotyping Methods......Page 544
Statistical Methods......Page 545
Haplotype-Specifi c Risks to Acute Skin Toxicity of Radiotherapy......Page 546
Combined Effects of Genotypes on the Risk of Acute Skin Toxicity After Radiotherapy......Page 548
Joint effects of the Genotypes in DNA Repair Genes and TP53 Arg72Pro......Page 550
Polymorphisms in DNA Repair Genes and the Risk of Acute Side Effects After Radiotherapy......Page 551
Polymorphisms in TP53 and p21 Genes and the Risk of Acute Side Effects After Radiotherapy......Page 553
Joint Effects of the Polymorphisms in DNA Repair Genes and TP53......Page 554
Epidemiological and Clinical Characteristics, Strengths and Limitations of the Study......Page 555
References......Page 556
Introduction......Page 560
Tumor Size......Page 561
Histological Tumor Type......Page 562
Tumor Growth Patterns......Page 563
Tissue Heterogenicity......Page 564
Breast Density......Page 565
Axillary Lymph Node Spread......Page 566
Blood Glucose Levels......Page 567
Data Acquisition and Data Analysis......Page 568
Recent Developments......Page 569
References......Page 570
Introduction......Page 573
Preoperative Evaluation Prior to Sentinel Lymph Node Surgery and Prophylactic Mastectomy......Page 575
Choice of Mapping Agent......Page 576
Site of Injection of Mapping Agents......Page 577
Surgical Technique......Page 579
Pathological Analysis of Sentinel Lymph Node......Page 581
Indications for Performing Sentinel Lymph Node Surgery at the Time of Prophylactic Mastectomy......Page 582
References......Page 583
Introduction......Page 587
Skin Incisions......Page 589
Tumor Removal......Page 590
Closure of Defect/Skin Closure......Page 592
Oncoplastics......Page 593
Minimally Invasive/Ablative Techniques......Page 595
References......Page 596
Introduction......Page 599
Enzyme Linked Immunosorbent Assay (ELISA)......Page 600
mmunohistochemistry......Page 601
mRNA Overexpression......Page 603
Quantitative Real-Time Reverse Transcription-PCR (RT-PCR)......Page 604
Fluorescence In Situ Hybridization (FISH)......Page 605
Chromogenic In Situ Hybridization (CISH)......Page 606
Quantitative Real-Time RT-PCR (qPCR)......Page 607
Impact on Surgical Resection......Page 612
Impact on Adjuvant Radiation Therapy......Page 613
Neoadjuvant Chemotherapy and Locoregional Therapy......Page 614
References......Page 615
Introduction......Page 617
Definition of Second Primary Tumors......Page 618
Analysis of Time to Diagnosis for Women with Second Primary Tumor......Page 619
Results......Page 620
Discussion......Page 624
References......Page 627
Breast Cancer in the Elderly......Page 629
Patient Comorbidities......Page 630
Determinants of Distant Metastatic Disease......Page 631
Lymph Node Evaluation in the Elderly......Page 632
Sentinel Node Biopsy Technique......Page 633
References......Page 634
Background......Page 637
Preclinical Data......Page 638
Efficacy of Combined TAM-RT Treatment......Page 639
Toxicities of Combined TAM-RT Treatment......Page 640
Methodology......Page 641
Patient Characteristics......Page 644
Treatment Delivery......Page 645
Complication-free Survival......Page 647
Discussion and Perspectives......Page 648
References......Page 649
Patient Characteristics......Page 652
Histological Analysis......Page 653
Prognosis......Page 654
Surgical Technique......Page 655
Radiotherapy......Page 656
Radiation Technique......Page 657
Chemotherapy Technique......Page 659
References......Page 660
Locally Advanced Breast Cancer......Page 663
Multidrug Resistance......Page 664
ABCC1 (MRP1) Protein......Page 665
Multidrug Resistance in Locally Advanced Breast Cancer......Page 666
Effects of MDR on Clinical Response to Chemotherapy......Page 668
Effects of MDR on Survival......Page 672
Modulation of ABC Transporters......Page 673
Future Perspectives......Page 674
References......Page 676
Introduction......Page 679
Methodology: FDG-PET and PET/CT Imaging......Page 680
Image Interpretation......Page 681
FDG-PET and PET/CT Imaging for Breast Cancer Recurrence......Page 682
References......Page 687
Introduction......Page 690
Patient Selection......Page 691
Dose of Radioisotope......Page 692
Lymphoscintigraphy......Page 693
References......Page 694
Introduction......Page 697
Cardiac Mortality......Page 698
Imaging Studies Assessing Cardiac Injury......Page 706
Daily Positioning......Page 709
Intensity Modulated Radiation Therapy......Page 710
Breath Hold Techniques......Page 713
References......Page 716
A......Page 720
B......Page 722
C......Page 724
D......Page 727
E......Page 729
F......Page 730
H......Page 732
I......Page 734
M......Page 735
N......Page 739
P......Page 740
R......Page 743
S......Page 744
T......Page 746
V......Page 749
Z......Page 750