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

About this book

• Discusses cancer diagnosis, therapy, and prognosis together in one volume
• Details the molecular processes that lead to the development and proliferation of cancer cells
• Includes recent major advances in cancer diagnosis and therapy assessment
• Features illustrations throughout that support the text
• Identifies patients with high likelihood of clinical benefits from a specific treatment

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.

Written for: Oncologists, clinicians, surgeons, medical teachers, hospital laboratories, medical students, drug industries and libraries

Keywords: Carcinoma

Table of contents

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 Köberle-Wührer, Michaela Riegler-Keil, Sabine Pöstlberger, 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 RECOMMENDATIONS
REFERENCES

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 Peiró

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