Breast Cancer Risk Reduction and Early Detection (eBook)

Preface 5
Contents 6
Contributors 8
Part I Prevention 10
1 Risk Factors 11
Key Issues 11
Introduction 12
Demographic Factors 12
Age 12
Race 12
Socioeconomic Status 13
Genetics 13
Family History 13
BRCA1 and BRCA2 14
Other Genes 14
Reproductive and Hormonal Factors 14
Menarche and Menopause 14
Parity 15
Age at First Birth 15
Lactation 15
Intrauterine Environment 15
Exogenous Hormones 16
Oral Contraceptive Pills 16
Postmenopausal Hormone Therapy 16
Estrogen Antagonists 17
Benign Breast Disease and Breast Density 17
Benign Breast Disease 17
Breast Density 18
Body Size and Physical Activity 19
Height 19
Obesity 19
Physical Activity 20
Behavioral Factors 20
Alcohol 20
Diet and Nutrition 21
Medications 21
Smoking 21
Environmental and Occupational Factors 22
Pesticides 22
Other Agents 22
Occupational Exposures 22
Radiation 23
Summary 23
References 24
2 Lifestyle Factors and Risk of Breast Cancer: A Review of Randomized Trial Findings 31
Key Issues 31
Introduction 32
Nutrition and Breast Cancer 32
Macronutrients 33
Micronutrients 34
Vitamin A/-carotene 34
Vitamin C 35
Vitamin E 35
Multiple Nutrient Supplements 38
Vitamin B and Folate 38
Calcium and Vitamin D 39
Medication Use 39
Hormone Therapy 39
Combination Estrogen/Progestin Therapy 40
Estrogen Alone 41
Further Analyses of Hormone Therapy Effects 42
Aspirin and NSAIDS and Other Anti-inflammatory Medicine 44
Discussion 44
References 46
3 Breast Cancer Chemoprevention 50
Key Issues 50
Introduction 51
Tamoxifen Trials 51
Royal Marsden 51
The National Surgical Adjuvant Breast and Bowel Project (NSABP) Breast Cancer Prevention Trial (BCPT) 52
The First International Breast Intervention Study -- I (IBIS-I) 53
The Italian Randomized Trial of Tamoxifen 54
Raloxifene Trials 54
The Multiple Outcomes of Raloxifene Evaluation (MORE) Study 54
The Continuing Outcomes Relevant to Evista (CORE) Trial 55
The Raloxifene Use for the Heart (RUTH) Trial 55
The Study of Tamoxifen and Raloxifene (STAR) 56
Summary 57
Unresolved Issues 58
Duration of Use 58
Optimal Age of Use 58
Use in Women with a Hereditary Predisposition to Breast Cancer 59
Underrepresentation of Minority Women 59
Underutilization of Chemopreventive Agents for Breast Cancer 59
Other Agents 59
Aromatase Inhibitors 60
Non-steroidal Anti-inflammatory Drugs (NSAIDs) 60
Retinoids 60
Vitamin D 61
Dietary Antioxidants 62
Future Directions 62
Personalizing Chemoprevention 62
Biomarkers for Risk Prediction 63
Combination Regimens 63
References 64
4 Surgical Management of Inherited Susceptibility to Breast Cancer 67
Key Issues 67
Introduction 67
Prophylactic Surgery 68
Bilateral Prophylactic Mastectomy (BPM) 69
BPM is Highly Effective 69
Pathology Often Finds Occult Cancer 71
Adverse Effects of BPM 72
Breast Reconstruction 72
Complications Are Common 73
Risk Reducing Salpingo-Oophorectomy (RRSO) 73
Morbidity and Potential Mortality Associated with RRSO 76
RRSO Complications 78
Determinants of Choice of RRSO and BPM 78
Comparing RRSO and BPM 79
Conclusion 80
References 80
Part II Early Detection 85
5 Clinical Breast Examination and Breast Self-Examination 86
Key Issues 86
Introduction 87
The Utility of CBE 88
The Role of CBE in Recognizing Breast Cancer 88
Sensitivity of CBE During Screening 90
The Limited Ability of Clinical Breast Examination to Identify Cancer 90
The Techniques of Clinical Breast Exam 94
The Choreography of CBE 94
The Central Importance of Palpation of the Supine Patient 95
Duration of CBE 96
The Nipple and Areola 97
Discharge 97
Understanding CBE 98
The Significance of Palpability 99
The Significance of Asymmetry 102
Changes Caused by Previous Surgery 102
What Cancer Feels Like 103
Breast Self-Examination 103
Teaching CBE and BSE 110
The Everpresent False Positive Screening Evaluation 116
When to Say When 117
References 117
6 Mammography 121
Key Issues 121
History of Mammography 122
Screening Mammography Today 122
Overview 122
Radiation Risk and Mammography 123
Screening Mammography in Practice 124
Breast Imaging Reporting and Data System (BIRADS) 125
Film Screen vs Digital Mammography 126
Special Situations: Imaging Implants 126
Breast Density 127
Interpretation of the Mammogram 127
Masses 128
Calcifications 129
Emerging Technologies in Digital Mammography: Digital Tomosynthesis and Contrast Enhanced Mammography 131
Conclusion 134
References 134
7 Current Status and Future Prospects in Breast Carcinoma of Positron Emission Tomography 137
Key Issues 137
PET in Breast Cancer: What Are the Oncologists Needs? 138
Detection and Characterization of the Primary Breast Tumor 138
Summary 139
Positron Emission Mammography (PEM) 140
Axillary Lymph Node Staging with FDG-PET 142
Summary 142
Characterization of Tumor Biology 142
Detection of Recurrent Disease 143
Promising Role of FDG-PET in Locally Advanced Breast Cancer (LABC) 143
Detection of Skeletal Involvement in Breast Cancer by FDG-PET 144
Assessment of Treatment Response in Breast Cancer 144
Summary 144
Imaging of Estrogen and Progesterone Receptor Functionality in Breast Cancer 145
PET/CT in Radiation Therapy Simulation 146
Changes in Patient Management Resulting from PET 147
Summary of the Role of PET in Breast Cancer: We Are Still Learning 147
Future Potential 147
References 147
8 Breast MRI 151
Key Issues 151
Introduction 152
Indications for Breast MRI 152
Initial Staging for Newly Diagnosed Breast Cancer 152
Patient with Axillary Node Metastases and Unknown Primary Malignancy 153
Monitoring Response to Neoadjuvant Chemotherapy 153
Evaluation of Equivocal Clinical and Imaging Findings 154
Screening High Risk Women 154
Performing Breast MRI 154
Equipment and Technique 155
Interpretation 156
Management of Abnormal Findings on Breast MRI 159
Emerging Technology: Proton Spectroscopy 163
References 164
9 Genetic and Molecular Approaches to Imaging Breast Cancer 167
Key Issues 167
Introduction 168
Compelling Clinical Need 168
Available Molecular Imaging Agents 168
Breast Cancer Genes as Diagnostic Targets 169
VPAC1 and VPAC2 169
IGF1R 170
EGFR 170
HER2 170
CCND1 170
MYCC 170
BCL2 171
Agents to Image Gene Expression in Animal Models and Patients 171
Peptide Probe Design 171
Hybridization Probe Design 172
Solid Phase Synthesis, Purification, Radiolabeling, And Stability 173
Cellular Specificity and Internalization 175
Administration, Pharmacokinetics, and Tissue Distribution 176
Whole Body Imaging 177
Oncogene Expression Imaging in Animal Models 177
MYCC 177
CCND1 178
BCL2 180
Oncogene Expression Imaging in Patients 180
VPAC1 180
Future Directions 181
References 183
10 Intraductal Approaches: Nipple Aspirate Fluid to Assist in BreastCancer Detection 187
Key Issues 187
Introduction 187
Methodology 188
NAF, if Proven Clinically Useful, Would Likely Be Cost Effective 189
Clinical Usefulness of the Technology 189
Sensitivity and Specificity 189
Initial Studies Focus on Feasibility 189
Studies Evaluating Cells in NAF 190
Studies Evaluating Extracellular Fluid in NAF 192
NAF as a Tool to Investigate the Presence of Mutagens in the Breast 194
Alternative Intraductal Evaluation Tools 195
Ductal Lavage 195
Mammary Ductoscopy (MD) 195
Are Imaging and Intraductal Results Complementary in Breast Cancer Detection? 196
What if the NAF is Abnormal and Standard Screening Studies Are Not? 196
Conclusion 196
Five-Year View 197
References 197
11 Intraductal Approaches: Mammary Ductoscopy and Ductal Lavage to Assist in the Diagnosis of Breast Cancer 201
Key Issues 201
Historical Development of Ductal Lavage and Ductoscopy 201
Ductal Lavage 202
Ductoscopy 203
Technical Considerations 204
References 207
12 Blood Markers 209
Key Issues 209
Introduction 210
Definitions 210
Discovery and Development of Biomarkers: The Problems 211
The Slow Evolution of a Biomarker: CEA in Breast Cancer 212
Existing Biochemical Tests and Breast Cancer 214
Multivariant Testing and Omics Technologies: The Methods and the Molecules 214
General Comments 214
Proteins and Proteomics 215
Glycoproteins and Carbohydrates 217
Lipids 218
Metabolites 218
Autoantibodies 219
Summary 219
References 219
13 Circulating Tumor Cells in Breast Cancer 222
Key Issues 222
Introduction 223
Definition of Occult Tumor Cells 223
Methods and Limitations for the Detection of Occult Tumor Cells 224
Diagnosis 225
Prognosis 225
Metastatic Breast Cancer 225
Early Breast Cancer 227
DTCs 227
CTCs 227
Detection of CTCs: Is it Always Prognostically Relevant? 228
DTCs vs CTCs 229
MRD and Breast Cancer Molecular Subtypes 230
Prediction 231
CTCs Phenotyping, Profiling and Genotyping 231
Chemotherapy and Hormonal Therapy 231
New Targeted Agents 232
CTCS as Prognostic and Predictive Tool: Is it Ready for Prime Time? 232
References 233
Subject Index 238