Methods of Cancer Diagnosis, Therapy and Prognosis: Breast Carcinoma (Methods of Cancer Diagnosis, Therapy and Prognosis, Volume 1)

This is the first book that discusses subjects of diagnosis, therapy, therapy assessment, and prognosis of breast cancer in one single volume. Cancer killed 6.7 million people around the world in 2002 and this figure is expected to rise to 10.1 million in 2020. Approximately, 189,510 new cases of breast cancer were reported in 2007 in the United States, and 40,910 died in the same year. Focusing on Breast Carcinoma, this first volume in the series Methods of Cancer Diagnosis, Therapy and Prognosis brings together 56 leading scientists from around the world to deliver a comprehensive treatise on all aspects of breast cancer, including diagnosis, treatments and prognosis. Scientists and clinicians have contributed state of the art chapters on their respective areas of expertise providing the reader a whole field view of breast cancer management. This fully illustrated volume: \* Presents a constructive evaluation of commonly used methods for elucidating primary and secondary cancer initiation, progression, relapse, and metastasis. \* Highlights methods of breast cancer diagnosis and treatment assessment including various imaging modalities such as ultrasound, computed tomography, magnetic resonance imaging, immunohistochemistry and histochemistry. \* Discusses detailed therapeutic protocols, including both their benefits and side-effects. \* Discusses examples of breast cancer treatments includingchemotherapy, radiation, chemoradiation, surgery, hormonal - and immunotherapy \* Details the molecular processes that lead to the development and proliferation of cancer cells \* Includes recent major advances in cancer diagnosis and therapy assessment Professor Hayat has summarized the problems associated with the complexities of research publications and has been successful in editinga must-read volume for oncologists, cancer researchers, medical teachers and students of cancer biology. 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 The enormity of the global healthcare costs vical. One-fifth of all cancers worldwide as a result of cancer infliction cannot be are caused by a chronic infection, for overemphasized. There are more than 100 example, human papilloma virus (HPV) types of cancers; any part of the body can causes cervical cancer and hepatitis B be affected. More than 11 million people virus (HBV) causes liver cancer. Tobacco are diagnosed with cancer every year, and use is the most common preventable cause it is estimated that there will be 16 mil- of cancer in the world. Approximately, lion new cases per year by the year 2020. 168,000 cancer deaths are expected to be In 2005, 7. 6 million people died of can- caused by tobacco use. Approximately, cer, that is, 13% of the 58 million deaths 40% of cancer could be prevented, mainly worldwide. It is estimated that 9 million by not using tobacco, having a healthy people will die from cancer worldwide in diet, being physically active, preventing 2015 and 11. 4 million will die in 2030. infections that may cause cancer, reduc- More than 70% of all cancer deaths occur ing exposure to sunlight, and avoidance of in low and middle income countries. excessive alcohol consumption and stress Five major cancer causing overall mor- (anger). A third of cancers could be cured talities per year worldwide are (WHO): if detected early and treated adequately. It is well established that scientific 1. Lung: 1.