BOOK
The Breast E-Book
Kirby I. Bland | Edward M. Copeland | V. Suzanne Klimberg | William J Gradishar
(2017)
Additional Information
Book Details
Abstract
Now in a single, convenient volume, The Breast: Comprehensive Management of Benign and Malignant Diseases, 5th Edition covers every clinically relevant aspect of the field: cancer, congenital abnormalities, hormones, reconstruction, anatomy and physiology, benign breast disease, and more. Building upon the strengths of previous editions, this updated volume by Drs. Kirby I. Bland, Edward M. Copeland III, V. Suzanne Klimberg, and William J Gradishar, includes the latest innovations in breast cancer detection and treatment in a practical, easy-to-use format ideal for today’s surgeons.
- Delivers step-by-step clinical guidance highlighted by superb illustrations that depict relevant anatomy and pathology, as well as medical and surgical procedures.
- Reflects the collaborative nature of diagnosis and treatment among radiologists, pathologists, surgeons, oncologists, and other health care professionals who contribute to the management of patients with breast disease.
- Offers the most comprehensive, up-to-date information on the diagnosis and management of, and rehabilitation following, surgery for benign and malignant diseases of the breast.
- Covers the latest developments in receptor modulation, targeted monoclonal antibodies, evolving inhibitors with triple-negative disease, and more.
- Discusses recent minimally invasive surgical techniques and new developments in oncoplastic breast conservation techniques.
- Contains significant updates to the "Management of Systemic Disease" section that reflect the latest advances in chemotherapy, hormonal resistance, and therapy.
Table of Contents
| Section Title | Page | Action | Price |
|---|---|---|---|
| Front Cover | cover | ||
| Endsheet 2 | IFC2 | ||
| Half title page | i | ||
| Michelangelo | ii | ||
| The Breast | iii | ||
| Copyright Page | iv | ||
| Dedication | v | ||
| Contributors | vi | ||
| Preface | xv | ||
| Acknowledgments | xvii | ||
| Table Of Contents | xviii | ||
| Video Contents | xxii | ||
| I History of the Therapy of Breast Cancer | 1 | ||
| 1 History of the Therapy of Breast Cancer | 1 | ||
| Ancient Civilizations | 1 | ||
| Chinese | 1 | ||
| Egyptian | 1 | ||
| Babylonian | 1 | ||
| Classic Greek Period (460–136 bce) | 1 | ||
| Greco-Roman Period (150 bce–ad 500) | 2 | ||
| Middle Ages | 2 | ||
| Christian | 2 | ||
| Jewish | 3 | ||
| Arabic | 4 | ||
| Renaissance | 4 | ||
| Eighteenth Century | 5 | ||
| Nineteenth Century | 7 | ||
| European Surgery | 7 | ||
| American Surgery | 8 | ||
| Evolution of a Standardized Radical Mastectomy | 9 | ||
| Twentieth Century | 12 | ||
| Surgery | 12 | ||
| Evolving Concepts Regarding Metastases in Breast Cancer | 12 | ||
| Radiotherapy | 14 | ||
| Hormonal Therapy | 15 | ||
| Chemotherapy | 16 | ||
| Adjuvant | 16 | ||
| Neoadjuvant | 16 | ||
| Mammography | 17 | ||
| Breast Reconstruction | 17 | ||
| Cancer Biology | 18 | ||
| Suggested Readings | 19 | ||
| References | 19.e1 | ||
| II Anatomy and Physiology of the Normal and Lactating Breast | 20 | ||
| 2 Anatomy of the Breast, Axilla, Chest Wall, and Related Metastatic Sites | 20 | ||
| Gross Anatomic Structure: Surface Anatomy | 20 | ||
| Form and Size | 20 | ||
| Extent and Location | 21 | ||
| Microscopic Anatomic Structure | 21 | ||
| Nipple and Areola | 21 | ||
| Inactive Mammary Gland | 21 | ||
| Active Mammary Glands: Pregnancy and Lactation | 22 | ||
| Hormonal Regulation of the Mammary Gland | 23 | ||
| Thoracic Wall | 24 | ||
| Axilla | 26 | ||
| Boundaries of the Axilla | 26 | ||
| Contents of the Axilla | 26 | ||
| Axillary Fasciae | 27 | ||
| Fascial Relationship of the Breast | 28 | ||
| Blood Supply of the Breast | 28 | ||
| Innervation of the Breast | 29 | ||
| Lymphatic Drainage of the Breast | 30 | ||
| Lymph Nodes of the Axilla | 30 | ||
| Sentinel Lymph Node Biopsy | 31 | ||
| Lymph Flow | 32 | ||
| Lymph Nodes of the Thoracic Wall | 34 | ||
| Lymph Nodes of the Thoracic Cavity | 35 | ||
| Venous Drainage of the Mammary Gland | 36 | ||
| Selected References | 36 | ||
| References | 36.e1 | ||
| 3 Breast Physiology | 37 | ||
| Embryology to Childhood | 37 | ||
| Morphology | 37 | ||
| Hormones | 37 | ||
| Regulatory Factors and Potential Genes | 38 | ||
| Clinical Correlates | 38 | ||
| Polythelia | 38 | ||
| Polymastia | 40 | ||
| Accessory (Ectopic) Axillary Breast Tissue | 41 | ||
| Amastia | 41 | ||
| Poland Syndrome | 41 | ||
| Newborn Nipple Discharge | 43 | ||
| Premature Thelarche | 43 | ||
| Precocious Puberty | 43 | ||
| Puberty | 44 | ||
| Morphology | 44 | ||
| Hormones | 44 | ||
| Menstrual Cycle | 45 | ||
| Regulatory Factors and Potential Genes | 46 | ||
| Clinical Correlates | 47 | ||
| Adolescent, Juvenile, or Virginal Hypertrophy | 47 | ||
| Tuberous Breast Deformity | 48 | ||
| Gynecomastia | 49 | ||
| Hypogonadotropism | 50 | ||
| Pregnancy | 50 | ||
| Morphology | 50 | ||
| Hormones | 51 | ||
| Regulatory Factors and Potential Genes | 51 | ||
| Clinical Correlates | 51 | ||
| Lactation | 53 | ||
| Morphology and Product | 53 | ||
| Hormones | 53 | ||
| Regulatory Factors and Potential Genes | 55 | ||
| Clinical Correlates | 55 | ||
| Delayed Onset of Lactation | 55 | ||
| Lactational Success | 55 | ||
| Impact on Breast Cancer Risk | 56 | ||
| Menopause | 56 | ||
| Morphology | 56 | ||
| Hormones | 56 | ||
| Clinical Correlates | 56 | ||
| Acknowledgment | 56 | ||
| Selected References | 56 | ||
| References | 56.e1 | ||
| 4 Discharges and Secretions of the Nipple | 57 | ||
| Introduction and Definitions | 57 | ||
| Nipple Aspiration Fluid: Characterization and Significance | 57 | ||
| Biochemical Composition of Nipple Aspiration Fluid | 60 | ||
| Minimally Invasive Techniques for Determining Risk of Breast Cancer | 61 | ||
| Ductal Lavage | 61 | ||
| Ductal Lavage Procedure. | 61 | ||
| Limitations of Ductal Lavage. | 62 | ||
| Ductal Lavage and Molecular Markers. | 63 | ||
| Random Periareolar Fine-Needle Aspiration | 64 | ||
| Summary | 64 | ||
| Clinical Evaluation and Management of the Patient With Nipple Discharge | 64 | ||
| Frequency and Etiology of Nipple Discharge | 64 | ||
| Intraductal Papilloma | 65 | ||
| Duct Ectasia | 65 | ||
| Lactational Bloody Nipple Discharge | 66 | ||
| Nonbreast Etiology | 66 | ||
| History | 66 | ||
| Examination | 67 | ||
| Imaging Evaluation | 67 | ||
| Mammography and Ultrasound | 67 | ||
| Ultrasound. | 67 | ||
| Magnetic Resonance Imaging of the Breast | 68 | ||
| Ductography-Galactography | 68 | ||
| Ductoscopy | 69 | ||
| Cytologic Evaluation of Nipple Discharge | 71 | ||
| Sample Collection | 71 | ||
| Sample Preparation | 71 | ||
| Cytologic Examination | 71 | ||
| Diagnosis and Surgical Intervention | 72 | ||
| Technique of Duct Excision | 72 | ||
| Technical Modifications for Duct Excision | 73 | ||
| Minimally Invasive Techniques for Biopsy of Intraductal Lesions | 75 | ||
| Algorithms for Management of Nipple Discharge | 76 | ||
| Outcomes | 76 | ||
| Summary | 77 | ||
| Selected References | 77 | ||
| References | 78.e1 | ||
| III Benign and Premalignant Lesions | 79 | ||
| 5 Etiology and Management of Benign Breast Disease | 79 | ||
| Breast Pain | 79 | ||
| Clinical Assessment | 79 | ||
| Classification | 79 | ||
| Nomenclature | 80 | ||
| Pathophysiology of Mastalgia | 80 | ||
| Pathogenesis and Etiology | 80 | ||
| Endocrine Influences | 80 | ||
| Nonendocrine Influences | 81 | ||
| Management of Mastalgia | 82 | ||
| Nutritional Therapy | 82 | ||
| Methylxanthines. | 82 | ||
| Low Dietary Fat. | 83 | ||
| Evening Primrose Oil and Gamma-Linolenic Acid. | 83 | ||
| Iodine. | 83 | ||
| Endocrine Therapy | 83 | ||
| Androgens | 84 | ||
| Testosterone. | 84 | ||
| Danazol. | 84 | ||
| Gestrinone. | 84 | ||
| Others | 84 | ||
| Luteinizing Hormone–Releasing Hormone Agonist. | 84 | ||
| Thyroid Hormone. | 84 | ||
| Nonendocrine Therapy | 84 | ||
| Bromocriptine. | 84 | ||
| Analgesics. | 85 | ||
| Abstention From Medications. | 85 | ||
| Refractory Mastalgia | 85 | ||
| Tamoxifen. | 85 | ||
| Trigger Point Injections for Extramammary Pain (Scapulothoracic Bursitis) Mimicking Noncyclical Breast Pain. | 86 | ||
| Psychiatric Approaches. | 86 | ||
| Surgical Approaches. | 86 | ||
| Ineffective Treatments | 86 | ||
| Diuretics. | 86 | ||
| Progesterones. | 86 | ||
| Vitamins. | 86 | ||
| Summary | 87 | ||
| Benign Breast Disorders | 87 | ||
| Nonproliferative Lesions of the Breast | 88 | ||
| Breast Cysts | 88 | ||
| Apocrine Metaplasia | 88 | ||
| Duct Ectasia and Periductal Mastitis | 88 | ||
| Mild Ductal Epithelial Hyperplasia | 88 | ||
| Fibroadenoma and Related Lesions | 89 | ||
| Fibroadenoma. | 89 | ||
| Complex Fibroadenoma. | 89 | ||
| Fibroadenomatosis (Fibroadenomatoid Mastopathy). | 89 | ||
| Tubular Adenoma. | 89 | ||
| Lactating Adenoma. | 89 | ||
| Hamartoma. | 90 | ||
| Adenolipoma/Lipoma. | 90 | ||
| Pseudoangiomatous Stromal Hyperplasia | 90 | ||
| Proliferative Lesions Without Atypia | 90 | ||
| Sclerosing Adenosis | 90 | ||
| Radial Scar and Complex Sclerosing Lesions | 90 | ||
| Florid Ductal Epithelial Hyperplasia | 90 | ||
| Intraductal Papilloma | 90 | ||
| Proliferative Lesions With Atypia | 91 | ||
| Atypical Lobular Hyperplasia | 91 | ||
| Atypical Ductal Hyperplasia | 91 | ||
| Flat Epithelial Atypia | 91 | ||
| Other Benign Breast Disorders | 91 | ||
| Nipple Discharge | 91 | ||
| Nipple Inversion | 92 | ||
| Epithelial Hyperplasia of Pregnancy | 92 | ||
| Adolescent Hypertrophy | 92 | ||
| Fat Necrosis | 92 | ||
| Subareolar Abscess and Fistula | 92 | ||
| Selected References | 92 | ||
| References | 92.e1 | ||
| 6 Mastitis and Breast Abscess | 93 | ||
| Mastitis | 93 | ||
| Presentation | 93 | ||
| Evaluation | 93 | ||
| Microbiology | 93 | ||
| Management | 94 | ||
| Antibiotics | 94 | ||
| Invasive Intervention | 94 | ||
| Early Abscess. | 94 | ||
| Aspiration. | 94 | ||
| Surgical Intervention. | 95 | ||
| Late Abscess. | 95 | ||
| Lactational Mastitis and Abscess | 95 | ||
| Periductal Abscess/Chronic Subareolar Abscess | 96 | ||
| Presentation | 96 | ||
| Causes | 96 | ||
| Factors | 97 | ||
| Treatment Plan | 97 | ||
| Surgical Management | 97 | ||
| Ductectomy | 97 | ||
| Resection of Major Mammary Ducts | 98 | ||
| Idiopathic Granulomatous Mastitis | 98 | ||
| Diagnosis | 99 | ||
| Etiology | 100 | ||
| Treatment | 100 | ||
| Treat Expectantly | 102 | ||
| Antibiotics | 102 | ||
| Steroids | 102 | ||
| Immune Modulators | 102 | ||
| Surgical Treatment | 103 | ||
| Authors’ Recommendations | 103 | ||
| Selected References | 103 | ||
| References | 103.e1 | ||
| 7 Gynecomastia | 104 | ||
| Prevalence | 104 | ||
| Clinical Presentation | 104 | ||
| Physiology | 104 | ||
| Development of the Male Breast | 104 | ||
| Neonatal Gynecomastia | 104 | ||
| Puberty | 104 | ||
| Pubertal Gynecomastia | 105 | ||
| Normal Circulating Male Estrogen Concentrations | 105 | ||
| Senile Gynecomastia | 105 | ||
| Histopathology | 105 | ||
| Pathophysiology | 106 | ||
| Estrogen Excess | 106 | ||
| Testicular Tumors | 106 | ||
| Leydig Cell Neoplasms. | 106 | ||
| Sertoli Cell Tumors. | 107 | ||
| Germ Cell Tumors. | 107 | ||
| Adrenal Cortex Neoplasms | 107 | ||
| Ectopic Human Chorionic Gonadotropin Production | 107 | ||
| Carcinoma of the Lung. | 107 | ||
| Hepatocellular Carcinoma. | 107 | ||
| Hermaphroditism | 107 | ||
| True Hermaphroditism. | 107 | ||
| Pseudohermaphroditism. | 108 | ||
| Altered Androgen-to-Estrogen Ratio | 108 | ||
| Hyperthyroidism | 108 | ||
| Liver Cirrhosis | 108 | ||
| Recovery From Starvation | 108 | ||
| Androgen Deficiency | 108 | ||
| Primary Testicular Failure | 108 | ||
| Klinefelter Syndrome. | 108 | ||
| Hereditary Defects of Androgen Biosynthesis. | 108 | ||
| Secondary Testicular Failure | 108 | ||
| Androgen Resistance Syndromes | 109 | ||
| Reifenstein Syndrome. | 109 | ||
| Kennedy Syndrome. | 109 | ||
| Increased Aromatase Activity | 109 | ||
| Chronic Renal Failure | 109 | ||
| Drugs Associated With Gynecomastia | 109 | ||
| Known Mechanisms | 109 | ||
| Unknown Mechanisms | 110 | ||
| Management of Gynecomastia | 110 | ||
| Evaluation of Male Breast Enlargement | 111 | ||
| Treatment of Male Breast Enlargement | 112 | ||
| Medical Therapy | 112 | ||
| Surgical Therapy | 112 | ||
| Summary | 114 | ||
| Gynecomastia in the Pubertal Male | 114 | ||
| Gynecomastia in the Aging Male | 114 | ||
| Gynecomastia Associated With Prostate Cancer Therapy | 115 | ||
| Selected References | 115 | ||
| References | 115.e1 | ||
| 8 Benign, High-Risk, and Premalignant Lesions of the Breast | 116 | ||
| Benign Lesions Without Cancer Risk Implications | 116 | ||
| Histopathology of Benign Breast Disease | 116 | ||
| Epithelial Hyperplasia and Proliferative Breast Disease | 118 | ||
| Definition and Background | 118 | ||
| Atypical Hyperplasia | 119 | ||
| Localized Sclerosing Lesions | 121 | ||
| Radial Scar and Complex Sclerosing Lesions | 123 | ||
| Duct Ectasia and Fat Necrosis | 124 | ||
| Duct Ectasia | 124 | ||
| Fat Necrosis | 124 | ||
| Fibroadenoma and Phyllodes Tumor | 124 | ||
| Fibroadenoma | 124 | ||
| Phyllodes Tumor | 126 | ||
| Pseudoangiomatous Stromal Hyperplasia | 127 | ||
| Papilloma | 127 | ||
| Histopathology | 127 | ||
| Columnar Cell Lesions | 128 | ||
| Selected References | 129 | ||
| References | 129.e1 | ||
| IV Pathology of Malignant Lesions | 130 | ||
| 9 In Situ Carcinomas of the Breast | 130 | ||
| Recent Insights Into the Unique Biology of Ductal Carcinoma in Situ and Lobular Carcinoma in Situ | 130 | ||
| Pathology of Ductal Carcinoma in Situ | 133 | ||
| Classification of Ductal Carcinoma in Situ | 137 | ||
| Extent of Disease | 138 | ||
| Extensiveness, Multicentricity, and Multifocality | 138 | ||
| Distribution | 139 | ||
| Mammographic Correlation | 139 | ||
| Margin Status | 139 | ||
| Risks of Evolution and Recurrence From Ductal Carcinoma in Situ | 140 | ||
| Receptor Proteins, Oncogenes, Tumor Suppressor Genes, and Ploidy | 140 | ||
| Special Types of Ductal Carcinoma in Situ With Special Implications | 142 | ||
| Hypersecretory Ductal Carcinoma in Situ | 142 | ||
| Paget Disease of the Nipple | 142 | ||
| Encysted, Noninvasive Papillary Carcinoma | 142 | ||
| Pathology of Lobular Carcinoma in Situ | 143 | ||
| Acknowledgment | 144 | ||
| Selected References | 144 | ||
| References | 144.e1 | ||
| 10 Infiltrating Carcinomas of the Breast | 145 | ||
| Molecular Classification | 145 | ||
| Histopathologic Classification | 147 | ||
| Histologic Types of Invasive Carcinoma | 147 | ||
| Invasive Mammary Carcinoma, Not Otherwise Specified | 147 | ||
| Invasive Lobular Carcinoma | 147 | ||
| Tubular Carcinoma | 148 | ||
| Invasive Cribriform Carcinoma | 149 | ||
| Mucinous Carcinoma | 149 | ||
| Medullary Carcinoma | 150 | ||
| Micropapillary Carcinoma | 150 | ||
| Secretory Carcinoma | 150 | ||
| Salivary Gland–Type Breast Carcinoma | 150 | ||
| Adenoid Cystic Carcinoma | 151 | ||
| Mucoepidermoid Carcinoma | 151 | ||
| Metaplastic Carcinoma | 151 | ||
| Prognosis of Invasive Breast Carcinoma | 151 | ||
| Tumor Stage | 151 | ||
| Histologic Grading | 152 | ||
| Additional Elements Occasionally Helpful | 153 | ||
| Prognostic Profiles in Breast Cancer | 154 | ||
| Predictive Profiles in Breast Cancer | 154 | ||
| Conclusion and Shortcomings of the Current System | 155 | ||
| Selected References | 155 | ||
| References | 155.e1 | ||
| 11 Mesenchymal Neoplasms and Primary Lymphomas of the Breast | 156 | ||
| Mesenchymal Neoplasms of the Breast | 156 | ||
| Breast Sarcoma | 156 | ||
| Fibroepithelial Neoplasms | 156 | ||
| Fibroadenoma | 156 | ||
| Phyllodes Tumor | 156 | ||
| Mammary Hamartoma | 158 | ||
| Fibroblastic and Myofibroblastic Neoplasms | 158 | ||
| Fibromatosis | 158 | ||
| Myofibroblastoma | 158 | ||
| Hemangiopericytoma | 159 | ||
| Pseudoangiomatous Stromal Hyperplasia | 159 | ||
| Inflammatory Myofibroblastic Tumor | 159 | ||
| Malignant Fibrous Histiocytoma | 159 | ||
| Vascular Neoplasms | 160 | ||
| Hemangioma | 160 | ||
| Angiomatosis | 160 | ||
| Hemangioendothelioma | 160 | ||
| Angiosarcoma and Related Syndromes | 160 | ||
| Lipomatous Neoplasms | 161 | ||
| Lipoma | 161 | ||
| Liposarcoma | 161 | ||
| Neural Neoplasms | 162 | ||
| Granular Cell Tumor | 162 | ||
| Benign Peripheral Nerve Sheath Tumors | 162 | ||
| Neurofibroma. | 162 | ||
| Schwannoma. | 162 | ||
| Myogenic Neoplasms | 162 | ||
| Leiomyoma | 162 | ||
| Leiomyosarcoma | 162 | ||
| Rhabdomyosarcoma | 162 | ||
| Osseous Neoplasms | 163 | ||
| Primary Breast Lymphoma | 163 | ||
| Clinical Features | 163 | ||
| Diagnosis and Staging | 163 | ||
| Radiologic Features | 163 | ||
| Staging. | 165 | ||
| Risk Factors/Pathogenesis | 165 | ||
| Pathology | 165 | ||
| Natural History and Prognosis | 166 | ||
| Patterns of Relapse | 167 | ||
| Treatment | 167 | ||
| Future Directions and Conclusion | 168 | ||
| Acknowledgment | 168 | ||
| Selected References | 168 | ||
| References | 168.e1 | ||
| 12 Paget Disease of the Breast | 169 | ||
| Pathogenesis | 169 | ||
| Histopathology | 170 | ||
| Clinical Presentation | 172 | ||
| Radiologic Findings | 174 | ||
| Management | 174 | ||
| Prognosis | 175 | ||
| Selected References | 176 | ||
| References | 176.e1 | ||
| 13 Primary and Secondary Dermatologic Disorders of the Breast | 177 | ||
| Primary Breast Dermatologic Disorders | 177 | ||
| Primary Congenital and Developmental Disorders | 177 | ||
| Amastia and Athelia | 177 | ||
| Hypoplasia and Associated Conditions | 177 | ||
| Hyperplasias, Hamartomas and Associated Conditions | 178 | ||
| Gynecomastia | 178 | ||
| Primary Inflammatory Disorders | 179 | ||
| Dermatoses of the Nipple and Breast | 179 | ||
| Eczematous Dermatitis (Nummular Eczema). | 179 | ||
| Allergic Contact Dermatitis. | 179 | ||
| Irritant Contact Dermatitis. | 180 | ||
| Dermatoses and Inflammatory Conditions Involving the Dermis | 180 | ||
| Mammary Duct Ectasia. | 180 | ||
| Radiation Dermatitis. | 180 | ||
| Hidradenitis Suppurativa. | 180 | ||
| Subareolar Abscess. | 180 | ||
| Ruptured Epidermal Inclusion Cyst. | 181 | ||
| Dermatoses and Inflammatory Conditions Involving the Subcutaneous Tissue | 181 | ||
| Fat Necrosis. | 181 | ||
| Panniculitis. | 181 | ||
| Mastitis. | 181 | ||
| Plasma Cell Mastitis. | 182 | ||
| Puerperal/Lactational Mastitis. | 182 | ||
| Lymphocytic Mastitis. | 182 | ||
| Granulomatous Lobular Mastitis. | 182 | ||
| Foreign-Body Mastitis. | 182 | ||
| Disorders of Keratinization | 182 | ||
| Axillary Granular Parakeratosis. | 182 | ||
| Primary Neoplastic Disorders | 183 | ||
| Primary Benign Neoplastic Disorders | 183 | ||
| Seborrheic Keratosis. | 183 | ||
| Lichen Planus–Like Keratosis. | 183 | ||
| Benign Cysts and Adnexal Tumors. | 183 | ||
| Erosive Adenomatosis of the Nipple. | 184 | ||
| Primary Malignant and Neoplastic Disorders | 185 | ||
| Paget’s Disease of the Breast. | 185 | ||
| Inflammatory Breast Carcinoma. | 186 | ||
| Atypical Vascular Lesion. | 186 | ||
| Angiosarcoma. | 186 | ||
| Malignant Adnexal Tumors. | 187 | ||
| Secondary Breast Dermatologic Disorders | 188 | ||
| Secondary Inflammatory Disorders | 188 | ||
| Infectious Disorders | 188 | ||
| Erythrasma. | 188 | ||
| Candidiasis. | 188 | ||
| Dermatophytosis (Tinea). | 188 | ||
| Varicella Zoster Virus. | 188 | ||
| Noninfectious Benign Lesions | 188 | ||
| Lichen Sclerosis et Atrophicus. | 188 | ||
| Seborrheic Dermatitis. | 188 | ||
| Psoriasis. | 189 | ||
| Drug Hypersensitivity Reactions. | 189 | ||
| Coumadin Necrosis. | 189 | ||
| Pyoderma Gangrenosum. | 189 | ||
| Mondor Disease. | 189 | ||
| Granuloma Annulare. | 190 | ||
| Acanthosis Nigricans. | 190 | ||
| Annular Erythema. | 190 | ||
| Sarcoidosis. | 190 | ||
| Pityriasis Rosea. | 190 | ||
| Lupus Panniculitis. | 190 | ||
| Darier Disease. | 190 | ||
| Connective Tissue Disorders. | 190 | ||
| Body Modification–Associated Dermopathy. | 191 | ||
| Secondary Neoplastic Disorders | 191 | ||
| Benign Disorders | 191 | ||
| Galactoceles. | 191 | ||
| Hair Disorders. | 191 | ||
| Vascular Neoplasms. | 192 | ||
| Smooth Muscle Neoplasms. | 192 | ||
| Fibrous Neoplasms. | 192 | ||
| Benign Melanocytic Lesions. | 192 | ||
| Malignant Disorders | 192 | ||
| Actinic Keratosis and Bowen Disease. | 192 | ||
| Squamous Cell Carcinoma. | 193 | ||
| Basal Cell Carcinoma. | 193 | ||
| Malignant Melanoma. | 193 | ||
| Dermatofibrosarcoma Protuberans. | 194 | ||
| Lymphomas. | 194 | ||
| Satellite Skin Metastasis. | 195 | ||
| Selected References | 196 | ||
| References | 196.e1 | ||
| 14 Breast Biomarker Immunocytochemistry | 197 | ||
| Estrogen Receptor: Historical Perspective | 197 | ||
| Progesterone Receptor: Historical Perspective | 198 | ||
| Receptor Status Assessment: Why Is It Important? | 198 | ||
| Scoring of Receptor Expression | 198 | ||
| American Society of Clinical Oncology/College of American Pathologists Recommendations | 199 | ||
| Correlation With Oncotype Dx | 199 | ||
| Repeat Immunohistochemical Studies on Recurrent and Metastatic Disease | 200 | ||
| Commonly Used Monoclonal Antibodies | 201 | ||
| Human Epidermal Growth Factor Receptor 2 | 201 | ||
| Historical Perspective | 201 | ||
| Standard Practice and New Challenges | 202 | ||
| Ki67 (Proliferation Marker) | 204 | ||
| E-Cadherin and p120 | 205 | ||
| Selected References | 206 | ||
| References | 206.e1 | ||
| V Natural History, Epidemiology, Genetics, and Syndromes of Breast Cancer | 207 | ||
| 15 Epidemiology of Breast Cancer | 207 | ||
| Descriptive Epidemiology | 207 | ||
| Differences in Subtypes of Breast Cancer by Race, Ethnicity and Geography | 207 | ||
| Sociodemographic Factors | 208 | ||
| Traditional Risk Factors for Breast Cancer | 209 | ||
| Benign Breast Disease | 209 | ||
| Lobular Carcinoma in Situ and Atypical Hyperplasia | 209 | ||
| Family History | 209 | ||
| Reproductive Factors | 209 | ||
| Other Risk Factors for Breast Cancer | 211 | ||
| Anthropometry | 211 | ||
| Endogenous Hormones | 214 | ||
| Dietary Fat and Serum Estradiol | 214 | ||
| Estrogen Metabolism | 214 | ||
| Diethylstilbestrol Exposure | 215 | ||
| Exogenous Hormones: Oral Contraceptives and Postmenopausal Hormone Therapy | 215 | ||
| Preeclampsia | 215 | ||
| Induced Abortion | 215 | ||
| Mammographic Breast Density | 216 | ||
| Exogenous Hormones and Mammographic Density | 216 | ||
| Dietary Fat and Mammographic Breast Density | 216 | ||
| Physical Activity | 216 | ||
| Alcohol Consumption | 216 | ||
| Smoking | 217 | ||
| Bone Mineral Density | 217 | ||
| Bisphosphonates | 217 | ||
| Night-Shift Work | 217 | ||
| Ionizing Radiation | 217 | ||
| Summary of Risk Factors for Breast Cancer | 218 | ||
| Selected References | 218 | ||
| References | 218.e1 | ||
| 16 Primary Prevention of Breast Cancer | 219 | ||
| Identifying Women at Risk | 219 | ||
| Breast Cancer Risk Models | 219 | ||
| Mammographic Density | 220 | ||
| Clinical Risk Counseling | 220 | ||
| Chemoprevention | 220 | ||
| Tamoxifen | 221 | ||
| Raloxifene | 221 | ||
| Chemoprevention Risk-Reduction Trials | 222 | ||
| Breast Cancer Prevention Trial | 222 | ||
| Other Outcomes in the Breast Cancer Prevention Trial | 223 | ||
| Other Unfavorable Outcomes in the Breast Cancer Prevention Trial | 223 | ||
| International Breast Cancer Intervention Study I | 224 | ||
| Summary of the SERM Chemoprevention Trials | 225 | ||
| Tamoxifen and Benign Breast Disease | 225 | ||
| SERMs in Lobular Carcinoma in Situ and Atypical Hyperplasia | 225 | ||
| Overall Risk of Developing Invasive Breast Cancer in Women With Atypical Hyperplasia | 227 | ||
| Assessing Risks and Benefits of Tamoxifen for Chemoprevention | 228 | ||
| Indications and Contraindications for Risk Reduction With SERMs | 228 | ||
| Effect of Tamoxifen in Carriers of Predisposing Genetic Mutations | 229 | ||
| Clinical Monitoring of Women Taking Tamoxifen | 229 | ||
| Tamoxifen Metabolites | 230 | ||
| Clinical Data With Raloxifene | 230 | ||
| Study of Tamoxifen and Raloxifene Trial | 230 | ||
| STAR Results After 81 Months of Follow-Up | 230 | ||
| STAR Trial and Potential Population Impact | 231 | ||
| Aromatase Inhibitors | 231 | ||
| Anastrozole | 232 | ||
| Exemestane | 232 | ||
| Expert Recommendations on the Use of Pharmacologic Interventions for Breast Cancer Risk Reduction | 232 | ||
| American Society of Clinical Oncology 2013 Clinical Practice Guideline | 233 | ||
| US Preventive Services Task Force Recommendations | 233 | ||
| National Comprehensive Cancer Network Recommendations | 234 | ||
| Tamoxifen Recommendation | 234 | ||
| Raloxifene Recommendation | 235 | ||
| Aromatase Inhibitor Recommendation | 236 | ||
| Summary | 236 | ||
| Selected References | 236 | ||
| References | 236.e1 | ||
| 17 Breast Cancer Genetics | 237 | ||
| The Value of Genetic Testing | 237 | ||
| Role of the Cancer Genetics Counselor | 237 | ||
| Identifying Mutation Carriers | 239 | ||
| Genetic Testing Technology | 240 | ||
| Sanger Sequencing | 240 | ||
| Next Generation Sequencing | 241 | ||
| Large Rearrangements | 241 | ||
| Classifying Variants | 242 | ||
| Variants of Uncertain Significance | 242 | ||
| Multigene Panels | 243 | ||
| Managing Cancer Risk | 244 | ||
| Reproductive and Lifestyle Factors | 244 | ||
| Enhanced Surveillance | 245 | ||
| Chemoprevention | 245 | ||
| Risk-Reducing Surgery | 245 | ||
| Bilateral Salpingo-Oophorectomy | 245 | ||
| Bilateral Prophylactic Mastectomy | 246 | ||
| Managing Cancer in Mutation Carriers | 246 | ||
| The Syndromes | 246 | ||
| BRCA1 and BRCA2 | 247 | ||
| PALB2 | 247 | ||
| TP53 | 247 | ||
| PTEN | 247 | ||
| CDH1 | 248 | ||
| ATM | 248 | ||
| CHEK2 | 248 | ||
| RAD51C | 248 | ||
| STK11 | 248 | ||
| BRIP1 | 248 | ||
| Selected References | 249 | ||
| References | 249.e1 | ||
| VI Prognostic Factors for Breast Cancer | 250 | ||
| 18 Clinically Established Prognostic Factors in Breast Cancer | 250 | ||
| Nomenclature | 250 | ||
| Prognostic Factors | 251 | ||
| Axillary Lymph Nodes | 251 | ||
| Tumor Size | 254 | ||
| Histologic Factors | 254 | ||
| Age and Race | 255 | ||
| Predictive and Prognostic Factors | 256 | ||
| Steroid Receptors | 256 | ||
| DNA and Proliferative Markers | 256 | ||
| Epidermal Growth Factor Receptor Family | 256 | ||
| Summary | 256 | ||
| Selected References | 257 | ||
| References | 257.e1 | ||
| 19 Molecular Prognostic Factors for Breast Carcinoma | 258 | ||
| Genomic Assays | 259 | ||
| Oncotype Dx | 259 | ||
| MammaPrint | 261 | ||
| Mammostrat | 261 | ||
| Prosigna Breast Cancer Prognostic Gene Signature Assay | 261 | ||
| Breast Cancer Index | 261 | ||
| EndoPredict Test | 262 | ||
| Genomic Grade Index | 262 | ||
| IHC4 | 262 | ||
| Nottingham Prognostic Index/NPI | 262 | ||
| MammaTyper | 262 | ||
| BreastPRS | 262 | ||
| BreastOncPx | 262 | ||
| Summary | 262 | ||
| Selected References | 263 | ||
| References | 263.e1 | ||
| 20 Risk Factors for Breast Carcinoma in Women With Proliferative Breast Disease | 264 | ||
| Nashville Breast Cohort Studies | 264 | ||
| Mayo Clinic Studies | 265 | ||
| Other Studies | 265 | ||
| Extent of Atypical Hyperplasia | 266 | ||
| Age, Family History, and Proliferative Disease | 267 | ||
| Complex Fibroadenoma and Proliferative Breast Disease | 267 | ||
| Effect of Time Since Biopsy on Risk of Breast Cancer | 269 | ||
| Radial Scar | 271 | ||
| Hormone Replacement Therapy in Women With Proliferative Disease | 271 | ||
| Selected References | 271 | ||
| References | 271.e1 | ||
| 21 Steroid Receptors in Breast Cancer | 272 | ||
| Estrogen Receptor | 272 | ||
| Historical Perspective | 272 | ||
| A Current View of the Molecular Mechanism of Estrogen Action | 274 | ||
| The Molecular Mechanism of Action of SERMs | 276 | ||
| The Molecular Mechanism of Action of SERDs | 276 | ||
| The Mechanisms of Drug Resistance to Long-Term Antihormone Therapy | 276 | ||
| Estrogen-Induced Apoptosis | 278 | ||
| Estrogen-Induced Apoptosis as an Interpretation of the Mortality Decreases After Long-Term Adjuvant Therapy and the WHI | 279 | ||
| The Progesterone Receptor | 280 | ||
| Androgen Receptor | 280 | ||
| Summary and Conclusions | 280 | ||
| Selected References | 281 | ||
| References | 281.e1 | ||
| VII Molecular Biology of Breast Carcinogenesis | 282 | ||
| 22 Molecular Oncology of Breast Cancer | 282 | ||
| Hallmarks of Cancer | 282 | ||
| Sustaining Proliferative Signaling | 282 | ||
| Evading Growth Suppressors | 283 | ||
| Resisting Cell Death | 284 | ||
| Enabling Replicative Immortality | 284 | ||
| Inducing Angiogenesis | 284 | ||
| Activation of Invasion and Metastasis | 284 | ||
| Genome Instability and Mutation | 284 | ||
| Tumor Promoting Inflammation | 285 | ||
| Reprogramming Energetics | 285 | ||
| Evading Immune Destruction | 286 | ||
| Normal Mammary Development and Carcinogenesis | 286 | ||
| Endogenous Hormones and Growth Factors | 286 | ||
| Prenatal or Fetal | 286 | ||
| Postnatal | 287 | ||
| Puberty | 287 | ||
| Pregnancy and Lactation | 288 | ||
| Postmenopausal Involution | 288 | ||
| Stem Cells | 288 | ||
| Stemness and Clonal Evolution | 288 | ||
| Clinical Perspective on Carcinogenesis and Progression | 288 | ||
| Molecular Profiling | 289 | ||
| Estrogen Receptor | 289 | ||
| Progesterone Receptor | 291 | ||
| HER2 Membrane Receptor | 292 | ||
| Molecular Subtypes of Breast Cancer | 293 | ||
| Molecular Subtypes of Triple-Negative Breast Cancers | 294 | ||
| Hereditary Breast Cancers | 294 | ||
| BRCA1 and BRCA2 | 294 | ||
| BRCA1 | 295 | ||
| BRCA2 | 296 | ||
| PTEN | 298 | ||
| CDH1 | 298 | ||
| Molecular Profiles of Sporadic Breast Cancers | 298 | ||
| Genetic Abnormalities in Breast Cancer | 298 | ||
| Oncogenes | 298 | ||
| Tumor Suppressor Genes | 298 | ||
| Driver and Passenger Alterations | 299 | ||
| Actionable Alterations | 299 | ||
| Common Somatic Mutations | 299 | ||
| p53 Tumor Suppressor | 299 | ||
| Copy Number Alterations | 301 | ||
| HER2 | 302 | ||
| FGFR1 and FGFR2 | 302 | ||
| Frequently Altered Molecular Pathways | 304 | ||
| Epigenetic Alterations | 304 | ||
| Methylation | 304 | ||
| Histone Acetylation | 304 | ||
| MicroRNAs | 304 | ||
| Tumor Microenvironment | 305 | ||
| Programmed Cell Death 1 and Programmed Death Ligand 1 | 305 | ||
| Integrins | 305 | ||
| BCL2 and Survivin | 305 | ||
| Biomarkers Used in Clinical Management of Breast Cancer | 305 | ||
| Markers for the Management of Early Breast Cancers | 306 | ||
| Markers for the Management of Advanced/Metastatic Breast Cancers | 306 | ||
| Circulating Tumor DNA | 306 | ||
| Conclusion | 306 | ||
| Acknowledgment | 307 | ||
| Selected References | 307 | ||
| References | 307.e1 | ||
| 23 Stem Cells in Breast Development and Cancer | 308 | ||
| Stem Cells in the Normal Breast | 308 | ||
| Markers of Normal Stem Cells | 308 | ||
| Mammary Stem Cell Regulatory Pathways | 309 | ||
| Stem Cells in Breast Cancer | 309 | ||
| Markers of Cancer Stem Cells | 310 | ||
| Key Signaling Pathways of Cancer Stem Cells | 310 | ||
| Relationship of Epithelial-Mesenchymal Transition and Cancer Stem Cell States | 311 | ||
| Cancer Stem Cells and the Tumor Microenvironment: Clinical Implications | 312 | ||
| Cancer Stem Cells and the Immune System | 312 | ||
| Cancer Stem Cell–Targeting Therapeutics | 313 | ||
| Acknowledgment | 314 | ||
| Selected References | 314 | ||
| References | 314.e1 | ||
| 24 Therapeutic Strategies for Breast Cancer | 315 | ||
| Epidemiology of Breast Cancer | 315 | ||
| Breast Cancer Risk Factors | 315 | ||
| The Natural History of Breast Cancer | 315 | ||
| Traditional Models for Breast Cancer Natural History | 315 | ||
| The Estrogen Paradox | 317 | ||
| From Descriptive Models to Biologically Informed Carcinogenesis | 317 | ||
| Breast Cancer Initiation | 317 | ||
| The Vascular Phase of Tumor Development: The Angiogenic Switch | 319 | ||
| Relationship Between Primary Tumor and Breast Cancer Metastases | 320 | ||
| Disseminated Tumor Cells | 320 | ||
| Tumor Heterogeneity | 321 | ||
| Molecular Subtypes of Breast Cancer | 321 | ||
| Limitations of Gene Expression Profiling Platforms | 321 | ||
| Intrapatient Heterogeneity and Clonal Evolution | 322 | ||
| Therapeutic Strategies for the Management of Invasive Breast Cancer | 322 | ||
| Surgical Treatment | 323 | ||
| Radiation Therapy | 324 | ||
| Medical Treatment | 324 | ||
| Chemotherapy | 324 | ||
| Chemotherapy for TNBC | 325 | ||
| VIII Screening and Diagnosis of Breast Disease | 331 | ||
| 25 Examination Techniques | 331 | ||
| Breast Self-Examination | 331 | ||
| Clinical Breast Examination | 332 | ||
| Imaging Modalities | 334 | ||
| Invasive Diagnostic Procedures | 335 | ||
| Selected References | 336 | ||
| References | 336.e1 | ||
| 26 Breast Imaging Screening and Diagnosis | 337 | ||
| Mammography | 337 | ||
| Screening Mammography | 337 | ||
| Diagnostic Mammography | 337 | ||
| Standardized Terminology for Mammography Reports | 339 | ||
| Normal Mammographic Findings | 339 | ||
| Abnormal Mammographic Findings | 340 | ||
| Masses | 340 | ||
| Benign Masses. | 341 | ||
| Malignant Masses. | 345 | ||
| Invasive Ductal Carcinoma of No Special Type. | 345 | ||
| Invasive Lobular Carcinoma. | 345 | ||
| Tubular Carcinoma. | 345 | ||
| Medullary Carcinoma. | 345 | ||
| Mucinous Carcinoma (Colloid Carcinoma). | 346 | ||
| Intracystic Papillary Carcinoma/Invasive Papillary Carcinoma. | 346 | ||
| Breast Metastases From Extramammary Malignancies. | 347 | ||
| Calcifications. | 347 | ||
| Benign Calcifications. | 348 | ||
| Malignant Calcifications. | 349 | ||
| Ductal Carcinoma in situ. | 350 | ||
| Invasive Carcinoma With Extensive Intraductal Component. | 351 | ||
| Indirect Signs of Breast Cancer | 352 | ||
| Architectural Distortions. | 352 | ||
| Asymmetries. | 352 | ||
| Abnormal Axillary Lymph Nodes. | 353 | ||
| Ultrasound | 353 | ||
| Standardized Terminology for Sonography Reports | 353 | ||
| Benign Masses | 353 | ||
| Malignant Masses | 354 | ||
| Magnetic Resonance Imaging | 355 | ||
| Standardized Terminology for MRI Reports | 356 | ||
| Typically Benign Findings | 356 | ||
| Typically Malignant Findings | 356 | ||
| Other Breast Imaging Technologies | 357 | ||
| Ductography (Galactography) | 357 | ||
| Imaging-Guided Interventional Procedures | 357 | ||
| Imaging-Guided Core Needle Biopsy | 357 | ||
| Imaging-Guided Preoperative Needle Localization | 359 | ||
| Staging and Imaging Follow-Up of Women With Breast Cancer | 359 | ||
| Evaluation for Distant Metastases | 359 | ||
| Follow-Up of the Conservatively Treated Breast | 359 | ||
| Follow-Up After Mastectomy | 361 | ||
| Selected References | 361 | ||
| References | 361.e1 | ||
| IX Clinical Trials: Biostatistical Applications | 362 | ||
| 27 Design and Conduct of Clinical Trials for Breast Cancer | 362 | ||
| Evolving Ethics and Regulation of Clinical Trials in the United States | 362 | ||
| Research Versus Clinical Care | 363 | ||
| What Is Not a Clinical Trial | 364 | ||
| Why Do Clinical Trials? | 364 | ||
| Designing Clinical Trials | 364 | ||
| Types of Clinical Trials | 364 | ||
| Cohort Trials | 364 | ||
| Prospective Cohort Study | 364 | ||
| Retrospective Cohort Study | 364 | ||
| Cross-Sectional Study Design | 365 | ||
| Case-Control Study Design | 365 | ||
| Interventional Trials | 366 | ||
| Uncontrolled Trials | 366 | ||
| Historical Controls | 366 | ||
| Controlled Trials | 366 | ||
| Trial Design for Phase I Oncology Studies | 367 | ||
| Trial Design for Phase II Oncology Studies | 367 | ||
| Gehan’s Design | 367 | ||
| Fleming’s Design | 368 | ||
| Simon’s Optimal Design | 368 | ||
| Simon’s Minimax Design | 368 | ||
| Comparisons of the Optimal and Minimax Designs | 368 | ||
| Fei and Shyr’s Balanced Design | 369 | ||
| Trial Design for Phase III Randomized Controlled Studies | 369 | ||
| Randomization Process | 371 | ||
| Sample Size Determination and Power Analysis | 372 | ||
| Monitoring Response Variables | 373 | ||
| Judging Quality of Clinical Trials: Level of Evidence | 375 | ||
| Reporting of Adverse Events for Clinical Trials | 375 | ||
| Conclusions | 376 | ||
| Selected References | 376 | ||
| Suggested Readings | 376 | ||
| References | 376.e1 | ||
| X Surgery for Benign and Malignant Diseases of the Breast | 377 | ||
| 28 Indications and Techniques for Biopsy | 377 | ||
| Fine-Needle Aspiration Biopsy | 377 | ||
| Procedure | 377 | ||
| Accuracy | 377 | ||
| Cytopathology | 378 | ||
| Direct Smear | 379 | ||
| Fluid Aspiration | 379 | ||
| Core Needle Biopsy | 379 | ||
| Ultrasound-Guided Biopsy | 380 | ||
| Stereotactic Core Needle Biopsy | 381 | ||
| Magnetic Resonance Imaging–Guided Biopsy | 382 | ||
| Open Surgical Biopsy | 382 | ||
| Choice of Anesthesia | 383 | ||
| Wire-Guided Localization | 383 | ||
| Intraoperative Ultrasound Guidance | 384 | ||
| Radioactive Seed Localization | 384 | ||
| Conclusion | 385 | ||
| Acknowledgment | 385 | ||
| Selected References | 385 | ||
| References | 385.e1 | ||
| 29 General Principles of Mastectomy | 386 | ||
| Topographic Surgical Anatomy | 388 | ||
| Neurologic Innervation of the Pectoral Muscles | 388 | ||
| Vascular Distribution | 390 | ||
| Lymphatic Drainage and Routes for Metastases | 390 | ||
| Evolution of Surgical Techniques for Mastectomy | 391 | ||
| Design of Incisions for Mastectomy in the Treatment of Breast Cancer | 394 | ||
| Central and Subareolar Primary Lesions | 394 | ||
| Lesions of the Upper Outer or Lower Inner Quadrants | 396 | ||
| Lesions of the Upper Inner Quadrants | 396 | ||
| Lesions of the Lower Outer Quadrants | 396 | ||
| High-Lying (Infraclavicular) Lesions | 396 | ||
| Skin-Sparing Mastectomy | 396 | ||
| Total Mastectomy With Limited Skin Excision: Rationale and Technique of the “Skin-Sparing” Total Mastectomy | 396 | ||
| Factors Affecting Local Recurrence | 396 | ||
| Biologic Factors: Effect on Local Recurrence | 397 | ||
| Tumor Volume (Size): Effect on Local Recurrence | 397 | ||
| Breast Skin Excision: Effect on Local Recurrence | 397 | ||
| Evolution of Breast Skin Excision With Mastectomy | 398 | ||
| Radical Mastectomy | 398 | ||
| Near-Total Excision of the Breast Skin Without Undermining to Develop Skin Flaps. | 398 | ||
| Wide Dissection of Skin Flaps With Extensive Skin Removal. | 398 | ||
| Wide Dissection of Thin Skin Flaps With Less Extensive Skin Removal. | 398 | ||
| Modified Radical Mastectomy | 398 | ||
| Skin Preservation Procedures | 398 | ||
| Technical Aspects of Skin-Sparing Mastectomy | 399 | ||
| Incision Design | 400 | ||
| Flap Elevation | 400 | ||
| Nipple-Sparing Mastectomy | 414 | ||
| Reconstruction Considerations | 414 | ||
| Overview of Reconstruction | 415 | ||
| Factors Influencing Immediate or Delayed Postmastectomy Reconstruction | 417 | ||
| Incisions for Axillary Dissection | 421 | ||
| Selected References | 421 | ||
| References | 421.e1 | ||
| 30 Halsted Radical Mastectomy | 422 | ||
| Historical Aspects for Development of Radical Mastectomy | 422 | ||
| Breast Cancer Treatment in the United States | 422 | ||
| Trends and Patterns of Care, 1971 to 1984 | 422 | ||
| Trends and Patterns of Care, 1985 to 2002 National Cancer Database—American College of Surgeons Commission on Cancer | 427 | ||
| Trends in Selection of Mastectomy Therapies, 2000 to 2016 | 430 | ||
| Indications for Use of the Halsted Radical Mastectomy | 436 | ||
| Technique of Radical Mastectomy | 437 | ||
| Selected References | 442 | ||
| References | 442.e1 | ||
| 31 Modified Radical Mastectomy and Simple Mastectomy | 443 | ||
| Modified Radical Mastectomy | 443 | ||
| Historical Evolution of the Surgical Technique | 443 | ||
| Retrospective Studies of the Modified Radical Mastectomy | 443 | ||
| Prospective Trials for the Modified Radical Mastectomy | 445 | ||
| Simple Mastectomy | 448 | ||
| Retrospective Studies of the Simple Mastectomy | 448 | ||
| Evolution of Simple Mastectomy With Sentinel Lymph Node Biopsy | 449 | ||
| Prospective Trials for the Simple Mastectomy With and Without Irradiation | 449 | ||
| Contralateral Prophylactic Mastectomy | 453 | ||
| Prophylactic Simple Mastectomy in High-Risk Patients | 455 | ||
| Role of Surgical Excision of Primary Tumor in Patients With Stage IV Disease | 456 | ||
| Modified Radical Mastectomy Technique | 457 | ||
| Anesthesia and Positioning | 457 | ||
| Sterile Skin Preparation | 457 | ||
| Skin Incision and Skin Flap Development | 457 | ||
| Removal of Breast | 458 | ||
| Operative Techniques for Variations of Simple Mastectomy | 458 | ||
| Dissection of Axillary Lymph Nodes | 460 | ||
| Closure | 461 | ||
| Postoperative Care | 461 | ||
| Selected References | 461 | ||
| References | 461.e1 | ||
| 32 Breast Conservation Therapy for Invasive Breast Cancer | 462 | ||
| Historical Perspective | 462 | ||
| Survival | 462 | ||
| Local Recurrence | 463 | ||
| Cosmetic Outcome | 467 | ||
| Patient Selection | 467 | ||
| Magnetic Resonance Imaging | 468 | ||
| Operative Technique | 469 | ||
| Localization | 469 | ||
| Incision | 469 | ||
| Tumor Removal | 469 | ||
| Quadrantectomy | 469 | ||
| Oncoplastic Surgery | 470 | ||
| Evaluation of Margins | 470 | ||
| Closure | 470 | ||
| Reexcision | 470 | ||
| Axilla | 472 | ||
| Radiation Therapy | 472 | ||
| Radiation and Its Role in Breast Conservation | 472 | ||
| Radiation Therapy Versus No Radiation Therapy | 473 | ||
| Radiation Therapy Sequencing | 474 | ||
| Radiation Therapy Technique | 474 | ||
| Radiation Dose: The Use of a Tumor Bed Boost | 475 | ||
| Length of Radiation Treatment | 475 | ||
| Selected References | 475 | ||
| References | 476.e1 | ||
| XI Breast Reconstruction | 477 | ||
| 33 Breast Reconstruction and Oncoplastic Surgery | 477 | ||
| Role of Reconstruction in Breast Cancer Treatment | 477 | ||
| Definition of the Mastectomy Deformity | 478 | ||
| Mastectomy | 478 | ||
| Partial Mastectomy/Lumpectomy | 478 | ||
| Reconstructive Surgical Methods | 478 | ||
| Tissue Expansion/Implants | 479 | ||
| Reconstruction With Acellular Dermal Matrix | 480 | ||
| Surgical Technique for Tissue Expander/Acellular Dermal Matrix | 481 | ||
| Myocutaneous Flaps | 481 | ||
| Surgical Technique of the Latissimus Flap | 481 | ||
| Surgical Technique of the Thoracoepigastric Flap | 483 | ||
| Surgical Technique of the Abdominal Transverse Rectus Abdominis Myocutaneous Flap | 484 | ||
| Oncoplastic Surgery | 485 | ||
| Reconstruction With Fat Grafting | 485 | ||
| Opposite Breast Considerations | 486 | ||
| Reduction Mammaplasty | 486 | ||
| Augmentation Mammaplasty | 489 | ||
| Nipple Reconstruction | 490 | ||
| Reconstruction Postradiation | 490 | ||
| Timing of Breast Reconstruction | 490 | ||
| Conclusions | 491 | ||
| Selected References | 491 | ||
| References | 491.e1 | ||
| XII Complications of Breast Surgery | 492 | ||
| 34 Wound Care and Complications of Mastectomy | 492 | ||
| Care of the Postmastectomy Wound | 492 | ||
| Complications of Mastectomy | 492 | ||
| Lymphedema | 492 | ||
| Wound Infection | 493 | ||
| Seroma | 493 | ||
| Pneumothorax | 496 | ||
| Tissue Necrosis | 496 | ||
| Hemorrhage | 496 | ||
| Injury to Neurovascular Structures | 497 | ||
| Deep Venous Thrombosis | 497 | ||
| Postmastectomy Pain Syndrome | 498 | ||
| Selected References | 498 | ||
| References | 498.e1 | ||
| 35 Quality Measures and Outcomes for Breast Cancer Surgery | 499 | ||
| Why Measure Quality? | 499 | ||
| Who Are the Stakeholders for Quality Measurement? | 499 | ||
| What Is the American History of Surgical Quality Measurement? | 500 | ||
| What Are Quality and Value? | 500 | ||
| What Are Safety in Surgery and Diagnostic Errors? | 500 | ||
| How Do We Identify a Gap in the Quality of Care? | 501 | ||
| Where Are the Databases for Quality and Clinical Outcomes Research? | 501 | ||
| How Do We Measure Quality? | 502 | ||
| What Is a Quality Measure, and Where Do We Find Them? | 503 | ||
| What Are the Quality Reporting Systems in the Public Sector? | 505 | ||
| What Is the Future of Public Quality Measurement Reporting? | 506 | ||
| How Do We Create the Best Quality Measures? | 507 | ||
| How Do We Rank a List of Many Quality Measures? | 507 | ||
| How Are Quality Measures Used? | 508 | ||
| How Do We Analyze Quality Data and Provide Fair Peer Comparisons? | 508 | ||
| What Is a Benchmark? | 508 | ||
| How Do We Improve Quality? | 509 | ||
| Do Quality Measurement and Improvement Programs Work? | 510 | ||
| Have the Breast-Specific Quality Measurement Programs Improved Breast Care? | 511 | ||
| What Are the Risks of Quality Measurement? | 511 | ||
| What Are the Future Challenges in Quality Measurement? | 512 | ||
| Conclusion | 512 | ||
| Selected References | 513 | ||
| References | 513.e1 | ||
| 36 Lymphedema in the Postmastectomy Patient | 514 | ||
| History | 514 | ||
| Anatomy | 515 | ||
| Lymph Nodes and Lymphatics Draining the Upper Extremity | 516 | ||
| Pathophysiology | 519 | ||
| Etiologic Risk Factors and Incidence | 521 | ||
| Incidence | 521 | ||
| Lymphedema From Radiation Treatment | 522 | ||
| Classification | 522 | ||
| Patient History and Measurement of Lymphedema | 522 | ||
| Nonoperative Management of Lymphedema | 524 | ||
| Complete Decongestive Physiotherapy | 525 | ||
| Exercise | 525 | ||
| Hyperbaric Oxygen | 526 | ||
| Benzopyrones | 526 | ||
| Prevention of Lymphedema | 526 | ||
| Sentinel Lymph Node | 526 | ||
| Nonoperative Management of the Axilla | 526 | ||
| Axillary Reverse Mapping and Reanatomosis | 527 | ||
| Axillary Reverse Mapping | 527 | ||
| LYMPHA (Lymphedema Microsurgical Preventive Healing Approach) | 527 | ||
| Operative Management of Lymphedema | 527 | ||
| Excisional Procedures | 527 | ||
| Tissue Transfer for Refractory Lymphedema | 528 | ||
| Liposuction | 528 | ||
| Lymphovenous Shunts | 528 | ||
| Postmastectomy Pain Syndrome | 529 | ||
| Lymphangiosarcoma: a Rare but Fatal Complication of Long-Standing Lymphedema | 529 | ||
| Summary | 530 | ||
| Acknowledgment | 530 | ||
| Selected References | 530 | ||
| References | 530.e1 | ||
| XIII Current Concepts and Management of Early Breast Carcinoma (Tis, Tmic, T1) | 531 | ||
| 37 Assessment and Designation of Breast Cancer Stage | 531 | ||
| Staging: Past, Present, and Future | 531 | ||
| Clinical, Pathologic, and Biological Markers and Factors in Determining Prognosis | 531 | ||
| Clinical Factors | 532 | ||
| Primary Tumor Characteristics | 532 | ||
| Tumor Size | 532 | ||
| Tumor Location | 533 | ||
| Tumor Histology | 534 | ||
| Tumor Grade | 534 | ||
| Histopathologic Features of Tumor | 534 | ||
| Estrogen and Progesterone Receptors | 535 | ||
| HER2/neu Expression | 535 | ||
| Tumor Growth Rate and Proliferation | 535 | ||
| Biological Markers | 536 | ||
| Lymph Node Status | 539 | ||
| Axillary Nodal Disease | 540 | ||
| Sentinel Lymph Node Mapping | 541 | ||
| Internal Mammary Nodal Disease | 541 | ||
| Supraclavicular Nodal Disease | 542 | ||
| Intramammary Nodal Disease | 542 | ||
| Pathologic Assessment of Lymph Nodes | 542 | ||
| Evolution of Staging Systems | 542 | ||
| Current Staging System | 544 | ||
| Specific Stages | 545 | ||
| T Stage (Tumor Size) | 545 | ||
| N Stage | 546 | ||
| M Stage | 548 | ||
| Stage Groupings | 548 | ||
| Histopathlogic Grade | 548 | ||
| Extent and Multicentricity of In Situ and Invasive Carcinoma | 549 | ||
| Case Studies | 550.e1 | ||
| Case 1 | 550.e1 | ||
| Case 2 | 550.e1 | ||
| Case 3 | 550.e1 | ||
| Case 4 | 550.e1 | ||
| Case 5 | 550.e2 | ||
| Biological Studies | 550 | ||
| Associated Factors | 550 | ||
| Clinical Follow-Up Studies | 550 | ||
| Clinical Implications of Multicentricity | 551 | ||
| Acknowledgment | 552 | ||
| Selected References | 552 | ||
| References | 552.e1 | ||
| 38 Lobular Carcinoma in Situ of the Breast | 553 | ||
| Historical Background | 553 | ||
| LCIS as a Premalignant Lesion | 553 | ||
| LCIS as a Risk Factor for Invasive Breast Cancer and Lobular Neoplasia | 553 | ||
| Continued Definition of LCIS as a Unique Stage 0 Preinvasive “Cancer” | 554 | ||
| LCIS Histopathology | 554 | ||
| Morphologic Features of LCIS | 554 | ||
| Pleomorphic LCIS | 555 | ||
| Immunohistologic Features and Molecular Genetics of LCIS | 556 | ||
| Clinical Presentation, Natural History, and Biologic Significance of LCIS | 556 | ||
| Clinical Features of LCIS | 556 | ||
| Risk of Subsequent Invasive Carcinoma After LCIS Diagnosis | 556 | ||
| Female Steroid Hormones and LCIS | 557 | ||
| Changing Incidence Rates of LCIS and the Influence or Exogenous Hormones on Lobular Carcinogenesis | 557 | ||
| Endocrine Chemoprevention for LCIS | 557 | ||
| Chemoprevention of Invasive Breast Cancer | 557 | ||
| Aromatase Inhibitors for Chemoprevention | 558 | ||
| Surgical Intervention for LCIS | 558 | ||
| Surgical Excisional Biopsy Showing LCIS | 558 | ||
| Core Needle Samples Showing LCIS | 558 | ||
| The Use of Breast Magnetic Resonance Imaging for Lobular Neoplasia | 559 | ||
| Breast Conservation in Patients Who Have LCIS Coincident With Invasive Cancer | 559 | ||
| Is There a Defined Role for Surgical Prophylaxis With LCIS? | 560 | ||
| Conclusions | 561 | ||
| Selected References | 561 | ||
| References | 561.e1 | ||
| 39 Ductal Carcinoma in Situ of the Breast | 562 | ||
| The Changing Nature of Ductal Carcinoma in Situ | 563 | ||
| Pathology | 563 | ||
| Classification | 563 | ||
| Progression to Invasive Breast Cancer | 564 | ||
| Immunohistochemical and Molecular Phenotypes in DCIS | 564 | ||
| Microinvasion | 564 | ||
| Multicentricity and Multifocality of Ductal Carcinoma in Situ | 564 | ||
| Detection and Diagnosis | 565 | ||
| Biopsy Techniques | 565 | ||
| Treatment | 566 | ||
| Treatment End Points for Patients With Ductal Carcinoma in Situ | 566 | ||
| Treatment Options | 566 | ||
| Mastectomy | 566 | ||
| Breast Conservation | 566 | ||
| Are We Overtreating Ductal Carcinoma in Situ? | 567 | ||
| Intraoperative Radiation Therapy for Ductal Carcinoma in Situ | 567 | ||
| Reasons to Consider Excision Alone | 567 | ||
| Common Use. | 567 | ||
| Anatomic. | 568 | ||
| Biological. | 568 | ||
| Pathology Errors. | 568 | ||
| Prospective Randomized Data. | 568 | ||
| Radiotherapy May Cause Harm. | 568 | ||
| Socioeconomic. | 568 | ||
| Increased Risk. | 568 | ||
| Only One Time. | 568 | ||
| Improved Patient Selection. | 568 | ||
| NCCN Guidelines. | 568 | ||
| Prospective Randomized Ductal Carcinoma in Situ Trials | 568 | ||
| Tamoxifen for Ductal Carcinoma in Situ | 569 | ||
| Determination of HER2/neu Status and Potential Benefit of Neoadjuvant Trastuzumab | 569 | ||
| Predicting Local Recurrence in Conservatively Treated Patients With DCIS | 570 | ||
| Treatment Selection for Patients With DCIS of the Breast Using the University of Southern California/Van Nuys Prognostic Index | 570 | ||
| Pathologic Evaluation | 570 | ||
| Statistical Analysis | 571 | ||
| Results | 571 | ||
| Discussion of Using USC/VNPI to Select Treatment | 572 | ||
| Using the USC/VNPI for Patients Undergoing Mastectomy | 573 | ||
| Oncotype DX Breast DCIS Score | 573 | ||
| Sentinel Node Biopsy for Ductal Carcinoma in Situ | 574 | ||
| Summary | 574 | ||
| Selected References | 574 | ||
| References | 575.e1 | ||
| 40 The New Paradigm | 576 | ||
| General Considerations | 576 | ||
| Leading the Oncoplastic Team | 576 | ||
| Rationale for Oncoplastic Breast Surgery | 577 | ||
| Reconstructive Goals | 577 | ||
| Preoperative Planning | 578 | ||
| Surgical Considerations | 579 | ||
| Oncoplastic Techniques | 579 | ||
| Simple Glandular Flap Techniques | 579 | ||
| Crescent, Hemibatwing, and Batwing Techniques | 579 | ||
| Vertical Mammaplasty, Inframammary Excision, and Central Excision Techniques | 581 | ||
| Round Block Mastopexy (Benelli) and Reduction Mammaplasty Techniques | 581 | ||
| Extreme Oncoplasty | 586 | ||
| Summary | 588 | ||
| Selected References | 589 | ||
| References | 589.e1 | ||
| 41 Therapeutic Value of Axillary Node Dissection and Selective Management of the Axilla in Small Breast Cancers | 590 | ||
| Lymphatic Function and Nodal Metastases | 590 | ||
| Axillary Anatomy and Evaluation | 592 | ||
| Axillary Radiotherapy | 597 | ||
| Therapeutic Role of Axillary Node Dissection | 598 | ||
| Selective Management of Axilla | 599 | ||
| Targeted Axillary Lymph Node Dissection | 601 | ||
| Selected References | 603 | ||
| References | 603.e1 | ||
| 42 Lymphatic Mapping and Sentinel Lymphadenectomy for Breast Cancer | 604 | ||
| History of Sentinel Node Concept in Breast Cancer | 604 | ||
| Evolution of Dye-Directed Sentinel Lymphadenectomy for Breast Cancer | 604 | ||
| Surgical Feasibility | 605 | ||
| Histopathologic Staging | 605 | ||
| Prospective Validation | 605 | ||
| Complete Nonsentinel Node Staging and Proof of Principle | 606 | ||
| Prospective Study of Sentinel Lymphadenectomy Alone for a Tumor-Free Sentinel Node | 607 | ||
| Identification of the Sentinel Node in Breast Cancer by Radiolocalization | 607 | ||
| Identification of the Sentinel Node With Preoperative Lymphoscintigraphy and Intraoperative Radioguided Surgery | 607 | ||
| Combined Technique of Vital Dye and Radioisotope | 607 | ||
| Global Experience With Sentinel Lymphadenectomy in Breast Cancer | 607 | ||
| Definition of the Sentinel Node | 607 | ||
| Multicenter Lymphatic Mapping Trials | 609 | ||
| Clinical, Pathologic, and Technical Aspects of Sentinel Lymphadenectomy | 610 | ||
| Patient Selection Criteria | 610 | ||
| Age | 611 | ||
| Gender | 611 | ||
| Body Habitus | 612 | ||
| Pregnancy and Lactation | 612 | ||
| Previous Breast or Axillary Surgery | 612 | ||
| Previous Excision | 612 | ||
| Tumor Features | 612 | ||
| Type of Carcinoma | 612 | ||
| Invasive Carcinoma. | 612 | ||
| Ductal Carcinoma In Situ and Ductal Carcinoma In Situ With Microinvasion. | 612 | ||
| Feasibility of Sentinel Lymph Node Dissection for Palpable Versus Nonpalpable Tumors | 613 | ||
| Multifocal or Multicentric Disease | 613 | ||
| Palpable Axillary Lymph Nodes | 614 | ||
| Applications of Sentinel Lymphadenectomy | 614 | ||
| Sentinel Lymphadenectomy and Operative Procedure | 614 | ||
| Preoperative Chemotherapy | 614 | ||
| Management of the Internal Mammary Lymph Sentinel Node | 615 | ||
| Predictors of Sentinel Node Metastases | 615 | ||
| Tumor Size and Risk of Sentinel Node Metastases | 615 | ||
| Number of Sentinel Nodes Removed | 616 | ||
| Significance of Micrometastases | 616 | ||
| Management of the Axilla When the Sentinel Node Is H&E Positive | 617 | ||
| Radiation Treatment of the Axilla | 618 | ||
| Technical Considerations | 618 | ||
| General Technical Considerations | 618 | ||
| Lymphatic Mapping With Vital Dye | 618 | ||
| Selection of Optimal Dye for Intraoperative Lymphatic Mapping | 618 | ||
| Complications of Dye Injection | 618 | ||
| Anesthetic Considerations | 621 | ||
| Vital Dye Injection Technique | 621 | ||
| Dissection Technique | 621 | ||
| Radiolocalization and Lymphatic Mapping With Isotopes | 622 | ||
| Radiopharmaceutical | 622 | ||
| Effect of Isotope Filtration on Dose and Volume of Injectate | 622 | ||
| Injection Site | 622 | ||
| Timing of Injection, Lymphoscintigraphy, Intraoperative Gamma-Probe Detection | 623 | ||
| Surgical Technique for Radioguided Sentinel Lymphadenectomy | 623 | ||
| Hottest Node | 624 | ||
| Pearls to Remember for the Combined Technique | 624 | ||
| Histopathologic Evaluation | 624 | ||
| False-Negative Sentinel Nodes | 625 | ||
| Predictors of Nonsentinel Node Metastases | 626 | ||
| Morbidity of Sentinel Lymphadenectomy | 626 | ||
| Learning Curve | 627 | ||
| Guidelines | 627 | ||
| Prospective Randomized Clinical Trials | 627 | ||
| NSABP B-32 | 627 | ||
| ACOSOG Z0010 | 628 | ||
| ACOSOG Z0011 | 628 | ||
| ALMANAC | 630 | ||
| AMAROS Trial | 630 | ||
| Summary | 630 | ||
| Selected References | 630 | ||
| References | 630.e1 | ||
| 43 Detection and Significance of Axillary Lymph Node Micrometastases | 631 | ||
| Definition and Classification of Axillary Lymph Node Micrometastases | 631 | ||
| Prognostic Significance of Axillary Lymph Node Micrometastases: Retrospective Data | 631 | ||
| Classification by Size of Axillary Lymph Node Metastasis | 631 | ||
| Classification by Frequency of Occult Axillary Lymph Node Metastases | 632 | ||
| The Ludwig Studies of Axillary Lymph Node Micrometastases | 632 | ||
| Logistical Hurdles in the Detection of Axillary Lymph Node Micrometastases | 633 | ||
| Role of Enhanced Pathology in Sentinel Lymph Node Biopsy | 633 | ||
| Improved Axillary Lymph Node Staging | 633 | ||
| Validation of the Sentinel Lymph Node Hypothesis | 633 | ||
| Reduction in the Rate of False-Negative Sentinel Lymph Node Biopsy | 633 | ||
| Risk of Nonsentinel Lymph Node Metastasis in Micrometastatic Sentinel Lymph Node–Positive Patients | 633 | ||
| Prognostic Significance of IHC-Detected Micrometastases: Prospective Studies | 634 | ||
| American College of Surgeons Oncology Group Z0010 Trial | 634 | ||
| National Surgical Adjuvant Breast and Bowel Project B-32 Trial | 635 | ||
| Surgery for SLN Micrometastases: A Shifting Paradigm | 635 | ||
| Unresolved Controversies | 635 | ||
| Are Immunohistochemistry-Positive Cells Metastases or Displacement Artifacts? | 635 | ||
| Can Pathologic Evaluation of SLNs Be Standardized? | 636 | ||
| Conclusions and Future Directions | 636 | ||
| Selected References | 636 | ||
| References | 636.e1 | ||
| 44 Intraoperative Evaluation of Surgical Margins in Breast Conserving Therapy | 637 | ||
| Frequency of Margin-Positive Partial Mastectomy | 639 | ||
| Pathologic Assessment of Margin Status and Specimen Handling | 639 | ||
| Gross Intraoperative Inspection of Tumor Margins | 639 | ||
| Cavity Shave Margin Technique | 639 | ||
| Frozen Section Analysis | 640 | ||
| Intraoperative Cytologic Evaluation by Touch Preparation | 640 | ||
| Intraoperative Ultrasound | 640 | ||
| Intraoperative Specimen Radiography | 641 | ||
| Other Approaches and Emerging Technology for Margin Analysis | 641 | ||
| Summary and Conclusions | 642 | ||
| Selected References | 642 | ||
| References | 642.e1 | ||
| 45 Surgical Management of Early Breast Cancer | 643 | ||
| Preoperative Evaluation | 644 | ||
| Surgical Options for Early Breast Cancer | 644 | ||
| Breast Conservation Surgery | 646 | ||
| Mastectomy | 649 | ||
| Axillary Evaluation | 649 | ||
| Adjuvant Radiotherapy | 652 | ||
| Outcome After Surgical Management of Breast Cancer | 653 | ||
| Management of the Elderly Patient | 653 | ||
| Invasive Lobular Breast Cancer | 655 | ||
| Family History of Breast Cancer | 655 | ||
| Minimally Invasive Ablative Therapies | 656 | ||
| Radiofrequency Ablation | 656 | ||
| Cryoablation | 657 | ||
| Interstitial Laser Therapy | 659 | ||
| Microwave Ablation | 659 | ||
| High-Intensity Focused Ultrasound Ablation | 660 | ||
| Irreversible Electroporation | 661 | ||
| Summary | 661 | ||
| Selected References | 662 | ||
| References | 662.e1 | ||
| XIV Therapy for Stages 0, I, and II Breast Cancer | 663 | ||
| 46 Biological Basis of Radiotherapy of the Breast | 663 | ||
| Radiotherapy Techniques: Introduction | 663 | ||
| Radiation Therapy Modalities: External Beam Versus Brachytherapy | 663 | ||
| Radiobiological Considerations | 664 | ||
| Anatomic Considerations for Radiation Delivery | 664 | ||
| External-Beam Techniques and Considerations | 664 | ||
| Standard Treatment Field Setup | 664 | ||
| Two-Dimensional Versus Three-Dimensional Conformal Versus Intensity-Modulated Radiation Therapy | 666 | ||
| Patient Positioning | 666 | ||
| Image-Guided Radiation Therapy (IGRT) | 667 | ||
| Boost Treatment Planning | 667 | ||
| Cardiac Avoidance in Breast Radiotherapy Planning | 667 | ||
| The Role of the Surgeon | 667 | ||
| Heart Blocks | 668 | ||
| Patient Positioning | 668 | ||
| Supine Breast Board | 668 | ||
| Prone Breast Board | 668 | ||
| Deep Inspiration Breathing Techniques | 668 | ||
| Accelerated Partial Breast Irradiation | 668 | ||
| Hypofractionation | 668 | ||
| 3D Planning | 668 | ||
| Protons | 668 | ||
| Accelerated Partial Breast Irradiation | 669 | ||
| Techniques for Delivery of APBI | 669 | ||
| External Beam/3D Conformal Radiation Therapy | 669 | ||
| Brachytherapy | 669 | ||
| Interstitial Brachytherapy. | 669 | ||
| Intracavitary Brachytherapy Balloon-Based Brachytherapy. | 669 | ||
| Intraoperative Photon/Electron Radiotherapy. | 670 | ||
| Conclusions | 670 | ||
| Selected References | 670 | ||
| References | 670.e1 | ||
| 47 Radiotherapy and Ductal Carcinoma in Situ | 671 | ||
| Randomized Trials Demonstrate Efficacy of Radiotherapy for Treatment of DCIS | 671 | ||
| Results With Excision Alone in Selected Patients | 673 | ||
| Factors Associated With Local Recurrence | 673 | ||
| Clinical Factors | 673 | ||
| Patient Factors | 673 | ||
| Pathologic Factors | 674 | ||
| Imaging Factors | 674 | ||
| Tools to Predict Risk | 674 | ||
| Tamoxifen and Radiotherapy | 674 | ||
| Radiation Treatment Techniques | 675 | ||
| Patterns of Recurrence and Results of Salvage Treatment | 675 | ||
| Radiation Therapy After Mastectomy | 676 | ||
| Conclusions | 676 | ||
| Selected References | 676 | ||
| References | 676.e1 | ||
| 48 Radiotherapy and Regional Nodes | 677 | ||
| Patient Selection | 677 | ||
| Positive Sentinel Node Without a Completion Axillary Dissection | 677 | ||
| Positive Sentinel Node and Completion Axillary Dissection With a Total of One to Three Positive Nodes | 678 | ||
| Radiotherapy Techniques for Regional Nodes | 680 | ||
| 3D Conformal Radiation | 681 | ||
| Multifield IMRT | 681 | ||
| Proton Therapy | 682 | ||
| Selected References | 687 | ||
| References | 687.e1 | ||
| 49 Postmastectomy Radiotherapy | 688 | ||
| Randomized Trials of Postmastectomy Radiotherapy | 688 | ||
| Controversies Surrounding Application of Randomized Trial Data in N1 Disease | 688 | ||
| Special Considerations | 690 | ||
| Patients With Node-Positive Disease and Undissected Axillae After Sentinel Lymph Node Biopsy | 690 | ||
| Postmastectomy Radiotherapy in Node-Negative Breast Cancer | 690 | ||
| Postmastectomy Radiotherapy in Patients Treated With Neoadjuvant Chemotherapy | 690 | ||
| Tumor Biology Considerations | 691 | ||
| Postmastectomy Radiotherapy and Reconstructive Surgery | 692 | ||
| Conclusions | 692 | ||
| Selected References | 692 | ||
| References | 692.e1 | ||
| 50 Breast Conserving Therapy for Invasive Breast Cancers | 693 | ||
| Randomized Trials Comparing Breast Conserving Surgery and Radiation Therapy With Mastectomy | 693 | ||
| Patient Selection for Breast Conserving Surgery and Radiation | 694 | ||
| Clinical Factors | 694 | ||
| Patient Age | 695 | ||
| Tumor Size | 695 | ||
| Gross Multifocal/Multicentric Disease | 696 | ||
| Genetic Factors | 696 | ||
| Race | 696 | ||
| Pathologic Factors | 696 | ||
| Margin Status | 697 | ||
| Tumor Subtyping | 698 | ||
| Other Pathologic Factors | 699 | ||
| Treatment Factors | 699 | ||
| Surgery | 699 | ||
| Radiation Boost | 699 | ||
| Adjuvant Systemic Therapy | 700 | ||
| Patient Selection Factors for Hypofractionated Whole Breast Irradiation | 700 | ||
| Timing of Radiation Therapy in Relation to Surgery and Systemic Therapy | 701 | ||
| Characteristics and Management of Local Failure After Breast Conserving Surgery and Radiation Therapy | 702 | ||
| Breast-Conserving Surgery Without Radiation Therapy | 703 | ||
| Conclusions | 704 | ||
| Selected References | 705 | ||
| References | 705.e1 | ||
| 51 Partial Breast Irradiation | 706 | ||
| Accelerated Partial Breast Irradiation | 706 | ||
| Interstitial Accelerated Partial Breast Irradiation | 706 | ||
| Applicator Accelerated Partial Breast Irradiation | 707 | ||
| External-Beam Accelerated Partial Breast Irradiation | 709 | ||
| Expert Consensus Statements | 710 | ||
| Future Directions | 710 | ||
| Intraoperative Radiation Therapy | 712 | ||
| Randomized Studies | 713 | ||
| Additional Studies | 714 | ||
| Boost | 714 | ||
| Future Directions | 714 | ||
| Conclusions | 715 | ||
| Selected References | 715 | ||
| References | 715.e1 | ||
| 52 Radiation Complications and Their Management | 716 | ||
| Fatigue and Myelosuppression | 716 | ||
| Radiation Dermatitis and Infections | 716 | ||
| Cosmesis and Breast-Related Symptoms | 719 | ||
| Rib Fracture | 721 | ||
| Brachial Plexopathy | 721 | ||
| Pulmonary Complications | 721 | ||
| Cardiac Complications | 722 | ||
| Second Malignancies | 724 | ||
| Complications in Patients With Collagen Vascular Disease | 724 | ||
| Conclusions | 725 | ||
| Selected References | 725 | ||
| References | 725.e1 | ||
| 53 Radiation Therapy for Locally Advanced Breast Cancer | 726 | ||
| Definition | 726 | ||
| Incidence | 726 | ||
| Outcomes | 727 | ||
| General Treatment Paradigms | 727 | ||
| Rationale for Use of Systemic Therapy | 727 | ||
| Rationale for Postmastectomy Radiation | 728 | ||
| Locoregional Recurrence Rates Without PMRT | 728 | ||
| Guideline Statements for PMRT and LABC | 728 | ||
| Studies for LABC | 729 | ||
| RT Alone for Operable LABC | 729 | ||
| Neoadjuvant Chemotherapy Followed by Either Resection or Radiation | 729 | ||
| Resection Followed by Systemic Therapy and Either Observation or Radiation | 729 | ||
| Neoadjuvant Systemic Therapy and Radiation for LABC | 729 | ||
| Inoperable LABC | 730 | ||
| Inflammatory Breast Carcinoma | 730 | ||
| Role for PMRT After NAC and Mastectomy | 730 | ||
| Potential Option for BCS After NAC for LABC | 730 | ||
| Locoregional Recurrence Risk on NSABP Trials of NAC and Implications for RT | 731 | ||
| Other Prognostic Factors and Future Directions | 731 | ||
| Locoregional Radiation Targets and Techniques for LABC | 732 | ||
| Conclusion | 734 | ||
| Selected References | 735 | ||
| References | 735.e1 | ||
| 54 Adjuvant Endocrine Therapy | 736 | ||
| Rationale for Adjuvant Endocrine Therapy | 736 | ||
| Who Is a Candidate for Adjuvant Endocrine Therapy? | 736 | ||
| Adjuvant Endocrine Therapy: Mechanism of Action | 737 | ||
| Selective Estrogen Receptor Modulators | 737 | ||
| Aromatase Inhibitors | 737 | ||
| Ovarian Ablation and Ovarian Function Suppression | 737 | ||
| Approaches to Adjuvant Endocrine Therapy for Invasive Early-Stage Breast Cancer | 737 | ||
| Evaluating Menopausal Status | 737 | ||
| Options for Postmenopausal Women With Invasive Early-Stage Breast Cancer | 737 | ||
| Tamoxifen Monotherapy for 5 Years: The Historical Standard | 737 | ||
| Tamoxifen Monotherapy for 10 Years | 738 | ||
| Aromatase Inhibitor Therapy for 5 Years | 738 | ||
| Sequential Therapy With Tamoxifen and an Aromatase Inhibitor (or Vice Versa) for 5 Years Total | 739 | ||
| Tamoxifen for 5 Years Followed by an Aromatase Inhibitor for Up to 10 Years Total | 742 | ||
| Aromatase Inhibitor for Longer Than 5 Years | 742 | ||
| Selecting an Adjuvant Endocrine Therapy Regimen for Postmenopausal Women With Early-Stage Invasive Hormone Receptor–Positive Breast Cancer | 743 | ||
| Options for Premenopausal Women With Invasive Early-Stage Breast Cancer | 743 | ||
| Tamoxifen Monotherapy for 5 Years | 743 | ||
| Tamoxifen Monotherapy for 10 Years | 743 | ||
| Tamoxifen for 5 Years Followed by an Aromatase Inhibitor for 5 Years | 743 | ||
| Ovarian Ablation or Ovarian Function Suppression Plus Tamoxifen or an Aromatase Inhibitor | 743 | ||
| Selecting an Adjuvant Endocrine Therapy Regimen for Premenopausal Women With Early-Stage Invasive Hormone Receptor–Positive Breast Cancer | 745 | ||
| Fertility Considerations in Premenopausal Women With Early-Stage Invasive Breast Cancer Undergoing Adjuvant Endocrine Therapy | 746 | ||
| Timing of Initiation of Adjuvant Endocrine Therapy | 747 | ||
| Moving Beyond Hormone Receptor Status: Biomarkers to Guide Therapeutic Decisions in Women With Invasive Early-Stage Hormone Receptor–Positive Breast Cancer | 747 | ||
| Estimating the Risk of Recurrence in Women Treated With Adjuvant Endocrine Therapy | 747 | ||
| Determining the Duration of Therapy: Biomarkers for Late Recurrence | 747 | ||
| Determining the Type of Endocrine Therapy: Biomarkers Suggestive of Benefit From Tamoxifen or Aromatase Inhibitor Therapy | 747 | ||
| Approaches to Adjuvant Endocrine Therapy for Ductal Carcinoma in Situ | 748 | ||
| Common Side Effects of Adjuvant Endocrine Therapy | 749 | ||
| Menopausal Symptoms | 749 | ||
| Sexual Dysfunction | 749 | ||
| Uterine Disorders | 749 | ||
| Thromboembolism | 749 | ||
| Cardiovascular Disorders | 749 | ||
| Mood Disturbances | 750 | ||
| Bone and Joint Pain | 750 | ||
| Loss of Bone Mineral Density, Osteoporosis, and Fractures | 750 | ||
| Quality of Life | 750 | ||
| Adherence to Adjuvant Endocrine Therapy | 750 | ||
| Conclusion | 751 | ||
| Selected References | 751 | ||
| References | 751.e1 | ||
| 55 Adjuvant and Neoadjuvant Systemic Therapies for Early-Stage Breast Cancer | 752 | ||
| Guidance in a Changing Landscape: St. Gallen and the National Comprehensive Cancer Network | 752 | ||
| Biology Defining Therapy: Breast Cancer Subtypes | 752 | ||
| Adjuvant Chemotherapy | 753 | ||
| First-Generation Regimens | 753 | ||
| Introduction of Anthracyclines | 753 | ||
| Addition of Taxanes to Anthracycline-Based Chemotherapy | 753 | ||
| Dose Density | 754 | ||
| Non–Anthracycline-Containing Regimens | 754 | ||
| Bone Marrow Transplant | 755 | ||
| ER-Positive Disease | 755 | ||
| Considering Chemotherapy | 755 | ||
| Genomic Profiling for Risk Stratification | 755 | ||
| When to Consider Chemotherapy for ER-Positive Disease | 756 | ||
| Tamoxifen | 756 | ||
| Aromatase Inhibitors | 757 | ||
| Ovarian Suppression | 757 | ||
| Optimal Endocrine Therapy for Pre- and Postmenopausal Women | 757 | ||
| Bisphosphonates in ER-Positive Breast Cancer | 758 | ||
| HER2-Positive Disease | 758 | ||
| Trastuzumab | 758 | ||
| Duration of Therapy | 758 | ||
| Deescalation of Therapy: Small HER2-Positive Tumors | 759 | ||
| Pertuzumab | 759 | ||
| Neoadjuvant Therapy | 759 | ||
| Advantages | 760 | ||
| Limitations | 760 | ||
| Breast and Axillary Assessments | 760 | ||
| Pathologic Complete Response | 761 | ||
| Selected References | 762 | ||
| References | 762.e1 | ||
| 56 HER2-Positive Breast Cancer | 763 | ||
| HER2 Biology | 763 | ||
| HER2 Pathology | 763 | ||
| HER2-Targeted Therapy | 764 | ||
| HER2 Metastatic Therapy | 764 | ||
| HER2 Adjuvant Therapy | 766 | ||
| Duration of Adjuvant Trastuzumab | 767 | ||
| Predictors of Response to Adjuvant Trastuzumab | 767 | ||
| Role of HER2 Variants | 767 | ||
| Role of Adjuvant Trastuzumab in Small, Lymph Node–Negative Tumors | 767 | ||
| Future Directions in HER2-Targeted Therapy | 767 | ||
| Selected References | 768 | ||
| References | 768.e1 | ||
| 57 Bisphosphonates in Early Breast Cancer | 769 | ||
| Bisphosphonates: Mechanism of Action | 769 | ||
| Types of Bisphosphonates | 769 | ||
| Rationale for an Anticancer Effect for Bisphosphonates | 769 | ||
| Clinical Trials on Adjuvant Bisphosphonates in Breast Cancer | 769 | ||
| Trials Using Clodronate | 769 | ||
| Trials Using Ibandronate | 771 | ||
| Trials Using Zoledronate | 771 | ||
| Individual Patient-Level Data Meta-Analysis | 771 | ||
| Rationale for Bisphosphonate Benefit in Postmenopausal Women | 771 | ||
| Safety of Adjuvant Bisphosphonates | 772 | ||
| When to Consider Adjuvant Bisphosphonates | 772 | ||
| Conclusions | 772 | ||
| Selected References | 772 | ||
| References | 772.e1 | ||
| 58 Oncofertility Options for Young Women With Breast Cancer | 773 | ||
| Oogenesis and Assessing Ovarian Reserve | 773 | ||
| Oogenesis | 773 | ||
| Assessing Ovarian Reserve | 773 | ||
| Gonadotoxicity of Cancer Therapies in Reproductive-Age Women | 774 | ||
| Surgery of the Breast | 774 | ||
| Impact of Radiation on Fertility | 774 | ||
| Chemotherapy in the Breast Cancer Setting | 774 | ||
| Biological Agents Used in the Treatment of Breast Cancer | 774 | ||
| Endocrine Therapy Used in the Treatment of Breast Cancer | 774 | ||
| Fertility Preservation Options | 775 | ||
| Oocyte or Embryo Cryopreservation | 775 | ||
| Ovarian Tissue Cryopreservation and Transplantation | 775 | ||
| Mitigating the Risk: The Role of Ovarian Transposition and Medical Suppression | 776 | ||
| Contraception and Cancer Therapy | 776 | ||
| Female Sexuality After Cancer Therapy | 776 | ||
| Pregnancy in Cancer Patients and Survivors | 776 | ||
| Talking With Patients and Families About Future Fertility | 777 | ||
| Oncofertility in Clinical Practice | 777 | ||
| Acknowledgment | 777 | ||
| Selected References | 777 | ||
| References | 777.e1 | ||
| XV Management of Advanced Local, Regional, and Systemic Disease | 778 | ||
| 59 Surgical Procedures for Advanced Local and Regional Malignancies of the Breast | 778 | ||
| Staging System Revisions and Implications | 778 | ||
| Pretreatment Evaluation, Diagnosis, and Management | 778 | ||
| Unimodal Treatment Approaches | 779 | ||
| Surgery | 779 | ||
| Radiotherapy | 780 | ||
| Multimodal Approaches | 780 | ||
| Early Trials | 780 | ||
| Chemotherapy | 781 | ||
| Endocrine Therapy | 783 | ||
| Targeted Therapy | 783 | ||
| Adjuvant Radiotherapy | 783 | ||
| Breast Conserving Surgery in Locally Advanced Breast Cancer | 784 | ||
| Axillary Staging | 784 | ||
| Axillary Lymphadenectomy | 784 | ||
| Rationale | 784 | ||
| Technique | 785 | ||
| Role of Sentinel Lymph Node Biopsy | 785 | ||
| Timing of Therapies | 786 | ||
| Full-Thickness Chest Wall Resection Revisited | 787 | ||
| Reconstructive Techniques | 788 | ||
| Timing of Breast Reconstruction | 788 | ||
| Immediate Reconstruction | 788 | ||
| Delayed Reconstruction | 788 | ||
| Options for Chest Wall Closure | 789 | ||
| Skin Grafts | 790 | ||
| Myocutaneous Flaps | 790 | ||
| Latissimus Dorsi Musculocutaneous Flap | 790 | ||
| Rectus Abdominis Transposition and Free Flaps | 791 | ||
| Vertical Rectus Abdominis Myocutaneous Flap | 791 | ||
| Transverse Rectus Abdominis Myocutaneous Flap | 792 | ||
| Pedicled | 792 | ||
| Free Rectus Musculocutaneous Flaps | 793 | ||
| Microvascular Composite Tissue Transplantation (Free Flaps) | 794 | ||
| Deep and Superficial Inferior Epigastric Artery Perforator Flaps | 794 | ||
| Pectoralis Major Flap | 794 | ||
| External Oblique Flap | 795 | ||
| Fasciocutaneous Flaps | 796 | ||
| Cutaneous and Local Flaps | 797 | ||
| Omental Flaps | 797 | ||
| Full-Thickness Chest Wall Defects and Prosthetic Materials | 798 | ||
| Radiotherapy and Reconstruction | 798 | ||
| Multidisciplinary Approach | 799 | ||
| Algorithm for Chest Wall Reconstruction | 799 | ||
| Selected References | 801 | ||
| References | 801.e1 | ||
| 60 Solitary Metastases | 802 | ||
| Liver | 802 | ||
| Lung | 803 | ||
| Bone | 804 | ||
| Brain | 805 | ||
| Summary | 806 | ||
| Selected References | 806 | ||
| References | 807.e1 | ||
| 61 Locoregional Recurrence After Mastectomy | 808 | ||
| Definitions | 808 | ||
| Incidence | 808 | ||
| Chest Wall Recurrences | 809 | ||
| Nodal Recurrences | 809 | ||
| Prior Radiation Therapy | 810 | ||
| Prior Systemic Therapy | 810 | ||
| Prior Neoadjuvant Chemotherapy | 811 | ||
| Genomic Characterization | 811 | ||
| Detection and Diagnosis | 811 | ||
| Survival After Locoregional Recurrence | 812 | ||
| Local Treatment | 812 | ||
| Radiation Therapy | 812 | ||
| Systemic Therapy | 813 | ||
| Conclusion | 813 | ||
| Selected References | 813 | ||
| References | 813.e1 | ||
| 62 Principles of Preoperative Therapy for Operable Breast Cancer | 814 | ||
| Coming of Age for Preoperative Systemic Therapy in Operable Breast Cancer | 814 | ||
| Rationale for Preoperative Systemic Therapy | 814 | ||
| Patient Selection for Preoperative Therapy in Operable Breast Cancer | 816 | ||
| Delivery of Optimal Preoperative Systemic Therapy | 816 | ||
| Preoperative Chemotherapy | 816 | ||
| Response-Adapted Preoperative Chemotherapy | 817 | ||
| Endocrine Therapy | 817 | ||
| On Treatment Monitoring and Posttreatment Management | 818 | ||
| Conclusions | 818 | ||
| Selected References | 818 | ||
| References | 818.e1 | ||
| 63 Locally Advanced Breast Cancer | 819 | ||
| Epidemiology | 819 | ||
| Survival | 819 | ||
| Diagnosis and Staging | 820 | ||
| Prognostic Factors | 820 | ||
| Evolution of Local Therapy | 820 | ||
| Combined Modality Treatment | 821 | ||
| Neoadjuvant Chemotherapy | 822 | ||
| Neoadjuvant Anti-HER2-Based Therapy | 823 | ||
| Neoadjuvant Antiestrogen Therapy | 824 | ||
| Assessment of Response to Neoadjuvant Chemotherapy | 827 | ||
| Predictors of Response to Neoadjuvant Therapy | 827 | ||
| Breast Conserving Surgery | 827 | ||
| Management of the Axilla: Historical Perspective and Current Recommendations | 828 | ||
| Management of the Axilla in Node-Negative Patients | 828 | ||
| Management of the Axilla in Node-Positive Patients | 829 | ||
| Management of the Axilla in Patients Undergoing Neoadjuvant Therapy | 830 | ||
| Treatment Summary | 831 | ||
| Selected References | 831 | ||
| References | 831.e1 | ||
| 64 Inflammatory Breast Cancer | 832 | ||
| Introduction and Historical Backdrop | 832 | ||
| Epidemiology | 832 | ||
| Diagnosis | 832 | ||
| Clinical Presentation | 832 | ||
| Imaging | 833 | ||
| Pathology | 834 | ||
| Medical Management and Trials | 835 | ||
| Postneoadjuvant/Adjuvant Strategies | 836 | ||
| Surgical Management | 837 | ||
| Radiation Management | 837 | ||
| Metastatic Disease | 838 | ||
| New Directions | 838 | ||
| Conclusion | 838 | ||
| Selected References | 838 | ||
| References | 838.e1 | ||
| 65 Neoadjuvant Chemotherapy and Radiotherapy | 839 | ||
| Molecular Subtypes of Breast Cancer and Response to Neoadjuvant Chemotherapy | 839 | ||
| Eligibility for Neoadjuvant Chemotherapy or Neoadjuvant Radiation Therapy | 840 | ||
| Evaluation of Candidates for Neoadjuvant Chemotherapy or Neoadjuvant Radiation Therapy | 841 | ||
| Outcomes and End Points of Neoadjuvant Therapy | 846 | ||
| Neoadjuvant Chemotherapy by Breast Cancer Subtypes | 847 | ||
| Targeted Therapy | 848 | ||
| Anti-HER2 Therapy | 848 | ||
| Antiangiogenic Therapy | 851 | ||
| Neoadjuvant Radiation Therapy for Breast Cancer | 851 | ||
| Response Assessment After Neoadjuvant Chemotherapy | 852 | ||
| Surgical Management After Neoadjuvant Chemotherapy | 852 | ||
| Staging the Axilla and Sentinel Lymph Node Procedure | 854 | ||
| Chemotherapy After Surgery | 855 | ||
| Radiation Therapy After Neoadjuvant Systemic Therapy | 855 | ||
| The Neoadjuvant Setting for Research and Drug Development | 856 | ||
| Conclusion and Future Directions | 856 | ||
| Selected References | 857 | ||
| References | 857.e1 | ||
| 66 Detection and Clinical Implications of Occult Systemic Micrometastatic Breast Cancer | 858 | ||
| Gene Expression Profiling of Breast Cancer Cells | 858 | ||
| Cancer Stem Cells | 859 | ||
| Methods for Analysis of CTCs | 859 | ||
| CTC Enrichment | 860 | ||
| Physical Properties | 860 | ||
| Biological Properties | 860 | ||
| CTC Detection | 862 | ||
| Protein-Based Strategies | 862 | ||
| Nucleic Acid–Based Strategies | 862 | ||
| Clinical Applications of CTCs | 862 | ||
| Metastatic Breast Cancer | 862 | ||
| Early Breast Cancer | 863 | ||
| Role of CTCs as a “Liquid Biopsy” in Metastatic Disease | 865 | ||
| Conclusions and Future Directions | 866 | ||
| Selected References | 866 | ||
| References | 866.e1 | ||
| 67 Management of the Intact Breast Primary in the Setting of Metastatic Disease | 867 | ||
| Retrospective Analyses of Primary Site Local Therapy | 868 | ||
| Surgical Resection of the Primary Tumor and Survival | 868 | ||
| Radiotherapy for the Primary Tumor and Survival | 870 | ||
| Effect of Primary Site Local Therapy on Locoregional Control | 870 | ||
| Retrospective Studies Questioning the Benefit of Primary Site Local Therapy in De Novo Stage IV Breast Cancer | 870 | ||
| Selection Biases in the Retrospective Analyses | 870 | ||
| Randomized Prospective Trials | 871 | ||
| Trials Requiring Induction Systemic Therapy | 871 | ||
| Trials Requiring Randomization to Locoregional Therapy Before Systemic Therapy | 872 | ||
| Prospective Registry Trial of de Novo Stage IV Breast Cancer Patients | 873 | ||
| Who Should Be Offered Locoregional Therapy | 874 | ||
| Conclusion | 875 | ||
| Selected References | 875 | ||
| References | 875.e1 | ||
| 68 Management of Bone Metastases in Breast Cancer | 876 | ||
| Pathophysiology | 876 | ||
| Clinical Presentation | 877 | ||
| Diagnosis | 877 | ||
| Surgical Management | 878 | ||
| Prophylactic Surgery | 878 | ||
| Pathologic Fractures | 878 | ||
| Radiotherapy | 879 | ||
| Radiotherapy Alone | 879 | ||
| Postoperative Radiotherapy | 879 | ||
| Side Effects | 880 | ||
| Retreatment With Radiotherapy | 880 | ||
| Radiopharmaceuticals | 880 | ||
| Systemic Osteoclast Inhibitors | 880 | ||
| Bisphosphonates | 880 | ||
| Denosumab | 882 | ||
| New Treatment Modalities | 883 | ||
| Conclusions and Recommendations | 883 | ||
| Acknowledgment | 884 | ||
| Selected References | 884 | ||
| References | 884.e1 | ||
| 69 Chemotherapy and HER2-Directed Therapy for Metastatic Breast Cancer | 885 | ||
| Epidemiology | 885 | ||
| Therapeutic Goals | 885 | ||
| Prognostication | 885 | ||
| Medical Evaluation in the Metastatic Setting | 886 | ||
| Local Therapy for Metastatic Breast Cancer | 886 | ||
| Breast Surgery in Patients With Metastatic Disease | 887 | ||
| Selecting Therapy for Metastatic Breast Cancer | 887 | ||
| Selecting a First-Line Regimen in HER2-Negative Metastatic Breast Cancer | 888 | ||
| Single-Agent Versus Combination Chemotherapy in HER2-Negative Breast Cancer | 888 | ||
| Chemotherapy for Metastatic Breast Cancer | 890 | ||
| Anthracyclines | 890 | ||
| Taxanes | 891 | ||
| Alkylating Agents | 893 | ||
| Antimetabolites | 893 | ||
| Fluoropyrimidines | 893 | ||
| Gemcitabine | 894 | ||
| Other Microtubule Inhibitors | 894 | ||
| Vinca Alkaloids | 895 | ||
| Treatment of HER2-Positive Metastatic Breast Cancer | 895 | ||
| Brain Metastases in HER2-Positive Breast Cancer | 899 | ||
| Novel Agents in Metastatic Breast Cancer | 899 | ||
| Historical Treatments for Metastatic Breast Cancer | 899 | ||
| Antiangiogenic Therapy | 899 | ||
| Treatment of Metastatic Bone Disease | 901 | ||
| Special Considerations | 902 | ||
| Treatment of Metastatic Breast Cancer in the Elderly | 902 | ||
| Management of Metastatic Triple-Negative Breast Cancer | 903 | ||
| Management of Metastatic Breast Cancer With Germline BRCA Mutations | 905 | ||
| Monitoring Response to Therapy | 905 | ||
| Future of Systemic Therapy for Metastatic Breast Cancer | 906 | ||
| Selected References | 906 | ||
| References | 906.e1 | ||
| 70 Endocrine Therapy for Breast Cancer | 907 | ||
| History of Endocrine Therapy in Breast Cancer | 907 | ||
| Linking the Course of Advanced Breast Cancer to Female Reproductive Organs | 907 | ||
| Recognizing Hormone Dependency for Certain Human Tumors | 907 | ||
| Understanding Estrogen Action and Developing Antiestrogens | 907 | ||
| The Modern Era of Endocrine Therapy | 907 | ||
| General Strategies for Targeting the Hormonal Axis | 908 | ||
| Hormone Assays | 908 | ||
| Predictive Power of ER/PR Status | 908 | ||
| Key Therapeutic Agents | 908 | ||
| Selective Estrogen Receptor Modulators | 908 | ||
| Tamoxifen | 908 | ||
| Efficacy. | 908 | ||
| Side Effects. | 908 | ||
| Metabolism. | 909 | ||
| Raloxifene | 910 | ||
| XVI Special Presentations of Breast Cancer | 967 | ||
| 75 Bilateral Breast Cancer | 967 | ||
| Risk Factors for Bilateral Breast Cancer | 967 | ||
| Age | 967 | ||
| Hereditary Breast Cancer | 967 | ||
| Family History | 968 | ||
| Radiation Exposure | 969 | ||
| Invasive Lobular Carcinoma | 969 | ||
| Lobular Carcinoma in Situ | 970 | ||
| Impact of Advanced Imaging and Adjuvant Therapy on Bilaterality | 970 | ||
| Magnetic Resonance Imaging and Contralateral Breast Cancer Detection | 970 | ||
| Chemotherapy | 970 | ||
| Tamoxifen | 971 | ||
| Declining Incidence of CBC | 971 | ||
| Prognosis of Bilateral Breast Cancer | 971 | ||
| Contralateral Prophylactic Mastectomy | 972 | ||
| Recommendations and Future Directions | 973 | ||
| Selected References | 973 | ||
| References | 973.e1 | ||
| 76 Male Breast Cancer | 974 | ||
| Epidemiology | 974 | ||
| Risk Factors | 974 | ||
| Clinical Features | 976 | ||
| Diagnosis | 976 | ||
| Pathology | 977 | ||
| Treatment of Localized and Locally Advanced Disease | 977 | ||
| Surgical Management | 977 | ||
| Management of Regional Nodes | 977 | ||
| Locally Advanced Disease | 978 | ||
| Adjuvant Radiation Therapy | 978 | ||
| Adjuvant Systemic Therapy | 978 | ||
| Treatment of Metastatic Disease | 979 | ||
| Prognosis | 979 | ||
| Survivorship Issues and Surveillance | 980 | ||
| Management Summary | 980 | ||
| Selected References | 980 | ||
| References | 980.e1 | ||
| 77 Local Recurrence, the Augmented Breast, and the Contralateral Breast | 981 | ||
| Locoregional Recurrence After Mastectomy | 981 | ||
| Recurrence in the Reconstructed Breast | 985 | ||
| Recurrence After Breast Conserving Therapy | 986 | ||
| Breast Cancer in the Augmented Breast | 989 | ||
| Breast Cancer After Skin-Sparing Mastectomy | 990 | ||
| Cancer Risk in the Contralateral Breast | 991 | ||
| Selected References | 992 | ||
| References | 992.e1 | ||
| 78 Carcinoma of the Breast in Pregnancy and Lactation | 993 | ||
| Prognosis and Historical Perspective | 993 | ||
| Diagnostic Evaluation and Staging During Pregnancy | 993 | ||
| Imaging Studies During Pregnancy | 994 | ||
| Breast Biopsy During Pregnancy | 994 | ||
| Pathologic Findings | 995 | ||
| Treatment | 995 | ||
| Surgery | 995 | ||
| Systemic Chemotherapy | 996 | ||
| Radiation Therapy | 997 | ||
| Special Issues | 998 | ||
| Therapeutic Abortion | 998 | ||
| BRCA Mutations and Pregnancy-Associated Breast Cancer | 998 | ||
| Conclusion | 998 | ||
| Selected References | 999 | ||
| References | 999.e1 | ||
| 79 Unknown Primary Presenting With Axillary Lymphadenopathy | 1000 | ||
| Incidence | 1000 | ||
| Diagnosis | 1000 | ||
| Selected Imaging | 1000 | ||
| Pathologic Evaluation | 1001 | ||
| Management | 1001 | ||
| Selected References | 1003 | ||
| References | 1003.e1 | ||
| 80 Clinical Management of the Patient at Increased or High Risk | 1004 | ||
| Breast Cancer Risk Assessment | 1004 | ||
| Qualitative Breast Cancer Risk Assessment | 1004 | ||
| Quantitative Breast Cancer Risk Assessment | 1004 | ||
| Risk Assessment Models Based on Nongenetic Factors | 1004 | ||
| Risk Assessment Models Based on Family History and Genetic Factors | 1005 | ||
| Breast Cancer Risk Assessment in the Clinical Setting | 1006 | ||
| Nongenetic Breast Cancer Risk Counseling | 1006 | ||
| Genetic Breast Cancer Risk Counseling | 1007 | ||
| Risk Management in the Clinical Setting | 1007 | ||
| Risk Reduction Options Based on Level of Risk | 1007 | ||
| High-Risk Women Secondary to Premalignant Lesions and Elevated Gail Risk | 1008 | ||
| High-Risk Women Secondary to Genetic Predisposition | 1008 | ||
| Risk-Based Screening Recommendations | 1009 | ||
| High-Risk Women Secondary to Elevated Gail Risk, Prior Thoracic Radiation at an Early Age, or Premalignant Lesions | 1009 | ||
| High-Risk Women Secondary to Known or Suspected Genetic Predisposition | 1010 | ||
| Conclusions | 1010 | ||
| Selected References | 1010 | ||
| References | 1010.e1 | ||
| XVII Survivorship, Follow-Up Care, and Rehabilitation of the Breast Cancer Patient | 1011 | ||
| 81 General Considerations for Follow-Up | 1011 | ||
| Surveillance for Locoregional Recurrences or New Primary Disease | 1011 | ||
| Detecting Distant Relapse | 1014 | ||
| Managing Long-Term and Late Effects of Cancer Treatment | 1015 | ||
| Lymphedema and Other Local Sequelae | 1015 | ||
| Osteoporosis | 1016 | ||
| Musculoskeletal Complaints | 1017 | ||
| Chemotherapy-Related Amenorrhea, Ovarian Dysfunction, and Infertility | 1017 | ||
| Pregnancy | 1017 | ||
| Hormonal Symptoms and Sexual Dysfunction | 1018 | ||
| Fatigue | 1019 | ||
| Cognitive Impairment | 1019 | ||
| Psychosocial Concerns | 1019 | ||
| Thrombosis | 1020 | ||
| Cardiac Disease | 1020 | ||
| Treatment-Related Cancers | 1021 | ||
| Non–Cancer-Related Care | 1022 | ||
| Survivorship Care Planning | 1022 | ||
| Conclusions and Future Directions | 1022 | ||
| Selected References | 1023 | ||
| References | 1023.e1 | ||
| 82 Management of Menopause in the Breast Cancer Patient | 1024 | ||
| What Is the Experience of Menopause in Women With Breast Cancer? | 1024 | ||
| Is Hormone Therapy an Option for Women With Breast Cancer? | 1024 | ||
| Alternatives to Estrogen-Based Therapy for Management of Vasomotor Symptoms | 1025 | ||
| Antidepressants | 1025 | ||
| Gabapentinoids | 1026 | ||
| Clonidine | 1026 | ||
| Progesterone Analogs | 1026 | ||
| Complementary and Alternative Methods | 1026 | ||
| Are Topical Estrogens an Option for Women With Breast Cancer? | 1027 | ||
| Alternatives to Topical Estrogens for Vulvovaginal Atrophy | 1027 | ||
| Depression | 1027 | ||
| Osteoporosis | 1028 | ||
| Cardiovascular Disease | 1028 | ||
| Conclusions | 1029 | ||
| Selected References | 1030 | ||
| References | 1030.e1 | ||
| 83 Rehabilitation | 1031 | ||
| Deconditioning | 1031 | ||
| Musculoskeletal System | 1031 | ||
| Cardiovascular System | 1031 | ||
| Cardiopulmonary Fitness | 1032 | ||
| Fatigue | 1032 | ||
| Screening and Diagnosis | 1032 | ||
| Treatment | 1032 | ||
| Upper Quadrant Dysfunction | 1033 | ||
| Pretreatment Upper Quadrant Function | 1033 | ||
| Biomechanics: Range of Motion, Scapular Control, Muscle Strength | 1033 | ||
| Correlation of Surgical Intervention and Upper Quadrant Dysfunction | 1033 | ||
| Impact of Impairments on Daily Activities | 1034 | ||
| Relationship to Physical Activity Level | 1034 | ||
| Screening | 1034 | ||
| Treatment | 1034 | ||
| Neuropathy | 1034 | ||
| Mononeuropathies | 1034 | ||
| Radiculopathy | 1035 | ||
| Brachial Plexopathy | 1035 | ||
| Chemotherapy-Induced Peripheral Neuropathy | 1035 | ||
| Taxanes | 1035 | ||
| Platinum Derivatives | 1035 | ||
| Vinca Alkaloids | 1035 | ||
| Diagnosis | 1036 | ||
| XVIII Medical and Legal Issues Specific to the Care of Breast Cancer | 1057 | ||
| 86 Delayed Diagnosis of Symptomatic Breast Cancer | 1057 | ||
| Magnitude of the Problem | 1058 | ||
| Definition of Delayed Diagnosis of Breast Cancer | 1061 | ||
| Patient-Associated Delays in Diagnosis | 1061 | ||
| Studies of Patient-Associated Delays in Diagnosis | 1061 | ||
| Physician-Associated Delays in Diagnosis | 1062 | ||
| Physician Factors in Delayed Diagnosis of Breast Cancer | 1062 | ||
| Interval of Diagnostic Delay | 1062 | ||
| Specialty Training of Physicians | 1063 | ||
| Diagnostic Workups Requested by Physicians | 1064 | ||
| Clinical Scenarios Leading to the Delayed Diagnosis of Breast Cancer by Physicians | 1064 | ||
| Triad of Error for Delay in Diagnosis of Breast Cancer | 1064 | ||
| Young Age. | 1065 | ||
| Self-Discovered Breast Mass. | 1066 | ||
| False-Negative Mammogram. | 1067 | ||
| Delays Related to Pregnancy-Associated (Gestational) Breast Cancer | 1069 | ||
| Delays in Diagnosis Related to Male Breast Cancer | 1070 | ||
| Delays in Diagnosis Related to False-Negative Fine-Needle Aspiration Biopsy | 1070 | ||
| Miscellaneous Factors Leading to the Delayed Diagnosis of Breast Cancer | 1071 | ||
| Influence of Delayed Diagnosis of Breast Cancer on Survival | 1071 | ||
| Studies Showing an Adverse Effect of Diagnostic Delay on Survival | 1071 | ||
| Studies Showing No Effect of Diagnostic Delay on Survival | 1075 | ||
| Conclusion: How to Prevent the Delayed Diagnosis of Breast Cancer—Synopsis of Clinical Risk Prevention | 1079 | ||
| Selected References | 1080 | ||
| References | 1080.e1 | ||
| Index | 1081 | ||
| A | 1081 | ||
| B | 1083 | ||
| C | 1087 | ||
| D | 1090 | ||
| E | 1092 | ||
| F | 1093 | ||
| G | 1094 | ||
| H | 1094 | ||
| I | 1096 | ||
| J | 1097 | ||
| K | 1097 | ||
| L | 1097 | ||
| M | 1099 | ||
| N | 1102 | ||
| O | 1104 | ||
| P | 1104 | ||
| Q | 1107 | ||
| R | 1107 | ||
| S | 1109 | ||
| T | 1112 | ||
| U | 1113 | ||
| V | 1113 | ||
| W | 1114 | ||
| X | 1114 | ||
| Y | 1114 | ||
| Z | 1114 | ||
| Endsheet 7 | IBC3 |