The Breast: Comprehensive Management of Benign and Malignant Diseases

Front Cover
Michelangelo
Title Page
Copyright Page
Dedication
Contributors
Preface
Acknowledgments
Contents
Video Contents
Section I: History of the Therapy of Breast Cancer
	1 History of the Therapy of Breast Cancer
		Ancient Civilizations
			Chinese
			Egyptian
			Babylonian
			Classic Greek Period (460–136 bce)
			Greco-Roman Period (150 bce–ad 500)
		Middle Ages
			Christian
			Jewish
			Arabic
		Renaissance
		Eighteenth Century
		Nineteenth Century
			European Surgery
			American Surgery
			Evolution of a Standardized Radical Mastectomy
		Twentieth Century
			Surgery
				Evolving Concepts Regarding Metastases in Breast Cancer
			Radiotherapy
			Hormonal Therapy
			Chemotherapy
				Adjuvant
				Neoadjuvant
			Mammography
			Breast Reconstruction
			Cancer Biology
		Suggested Readings
		References
Section II: Anatomy and Physiology of the Normal and Lactating Breast
	2 Anatomy of the Breast, Axilla, Chest Wall, and Related Metastatic Sites
		Gross Anatomic Structure: Surface Anatomy
			Form and Size
			Extent and Location
		Microscopic Anatomic Structure
			Nipple and Areola
			Inactive Mammary Gland
			Active Mammary Glands: Pregnancy and Lactation
			Hormonal Regulation of the Mammary Gland
			Thoracic Wall
			Axilla
				Boundaries of the Axilla
				Contents of the Axilla
				Axillary Fasciae
			Fascial Relationship of the Breast
			Blood Supply of the Breast
			Innervation of the Breast
		Lymphatic Drainage of the Breast
			Lymph Nodes of the Axilla
			Sentinel Lymph Node Biopsy
			Lymph Flow
			Lymph Nodes of the Thoracic Wall
			Lymph Nodes of the Thoracic Cavity
			Venous Drainage of the Mammary Gland
		Selected References
		References
	3 Breast Physiology
		Embryology to Childhood
			Morphology
			Hormones
			Regulatory Factors and Potential Genes
			Clinical Correlates
			Polythelia
			Polymastia
			Accessory (Ectopic) Axillary Breast Tissue
			Amastia
			Poland Syndrome
			Newborn Nipple Discharge
			Premature Thelarche
			Precocious Puberty
		Puberty
			Morphology
			Hormones
			Menstrual Cycle
			Regulatory Factors and Potential Genes
			Clinical Correlates
			Adolescent, Juvenile, or Virginal Hypertrophy
			Tuberous Breast Deformity
			Gynecomastia
			Hypogonadotropism
		Pregnancy
			Morphology
			Hormones
			Regulatory Factors and Potential Genes
			Clinical Correlates
		Lactation
			Morphology and Product
			Hormones
		Regulatory Factors and Potential Genes
			Clinical Correlates
				Delayed Onset of Lactation
				Lactational Success
				Impact on Breast Cancer Risk
		Menopause
			Morphology
			Hormones
			Clinical Correlates
		Acknowledgment
		Selected References
		References
	4 Discharges and Secretions of the Nipple
		Introduction and Definitions
			Nipple Aspiration Fluid: Characterization and Significance
				Biochemical Composition of Nipple Aspiration Fluid
			Minimally Invasive Techniques for Determining Risk of Breast Cancer
				Ductal Lavage
					Ductal Lavage Procedure.
					Limitations of Ductal Lavage.
					Ductal Lavage and Molecular Markers.
				Random Periareolar Fine-Needle Aspiration
				Summary
		Clinical Evaluation and Management of the Patient With Nipple Discharge
			Frequency and Etiology of Nipple Discharge
				Intraductal Papilloma
				Duct Ectasia
				Lactational Bloody Nipple Discharge
				Nonbreast Etiology
			History
			Examination
			Imaging Evaluation
				Mammography and Ultrasound
					Ultrasound.
				Magnetic Resonance Imaging of the Breast
				Ductography-Galactography
				Ductoscopy
			Cytologic Evaluation of Nipple Discharge
				Sample Collection
				Sample Preparation
				Cytologic Examination
		Diagnosis and Surgical Intervention
			Technique of Duct Excision
			Technical Modifications for Duct Excision
			Minimally Invasive Techniques for Biopsy of Intraductal Lesions
			Algorithms for Management of Nipple Discharge
			Outcomes
		Summary
		Selected References
		References
Section III Benign and Premalignant Lesions
	5 Etiology and Management of Benign Breast Disease
		Breast Pain
			Clinical Assessment
				Classification
			Nomenclature
			Pathophysiology of Mastalgia
				Pathogenesis and Etiology
				Endocrine Influences
				Nonendocrine Influences
			Management of Mastalgia
				Nutritional Therapy
					Methylxanthines.
					Low Dietary Fat.
					Evening Primrose Oil and Gamma-Linolenic Acid.
					Iodine.
				Endocrine Therapy
					Androgens
						Testosterone.
						Danazol.
						Gestrinone.
					Others
						Luteinizing Hormone–Releasing Hormone Agonist.
						Thyroid Hormone.
				Nonendocrine Therapy
					Bromocriptine.
					Analgesics.
					Abstention From Medications.
				Refractory Mastalgia
					Tamoxifen.
					Trigger Point Injections for Extramammary Pain (Scapulothoracic Bursitis) Mimicking Noncyclical Breast Pain.
					Psychiatric Approaches.
					Surgical Approaches.
					Ineffective Treatments
						Diuretics.
						Progesterones.
						Vitamins.
				Summary
		Benign Breast Disorders
			Nonproliferative Lesions of the Breast
				Breast Cysts
				Apocrine Metaplasia
				Duct Ectasia and Periductal Mastitis
				Mild Ductal Epithelial Hyperplasia
				Fibroadenoma and Related Lesions
					Fibroadenoma.
					Complex Fibroadenoma.
					Fibroadenomatosis (Fibroadenomatoid Mastopathy).
					Tubular Adenoma.
					Lactating Adenoma.
					Hamartoma.
					Adenolipoma/Lipoma.
				Pseudoangiomatous Stromal Hyperplasia
			Proliferative Lesions Without Atypia
				Sclerosing Adenosis
				Radial Scar and Complex Sclerosing Lesions
				Florid Ductal Epithelial Hyperplasia
				Intraductal Papilloma
			Proliferative Lesions With Atypia
				Atypical Lobular Hyperplasia
				Atypical Ductal Hyperplasia
				Flat Epithelial Atypia
			Other Benign Breast Disorders
				Nipple Discharge
				Nipple Inversion
				Epithelial Hyperplasia of Pregnancy
				Adolescent Hypertrophy
				Fat Necrosis
				Subareolar Abscess and Fistula
		Selected References
		References
	6 Mastitis and Breast Abscess
		Mastitis
			Presentation
			Evaluation
			Microbiology
			Management
				Antibiotics
				Invasive Intervention
					Early Abscess.
					Aspiration.
					Surgical Intervention.
					Late Abscess.
		Lactational Mastitis and Abscess
		Periductal Abscess/Chronic Subareolar Abscess
			Presentation
			Causes
			Factors
			Treatment Plan
			Surgical Management
				Ductectomy
				Resection of Major Mammary Ducts
		Idiopathic Granulomatous Mastitis
			Diagnosis
			Etiology
			Treatment
				Treat Expectantly
				Antibiotics
				Steroids
				Immune Modulators
				Surgical Treatment
				Authors’ Recommendations
		Selected References
		References
	7 Gynecomastia
		Prevalence
		Clinical Presentation
		Physiology
			Development of the Male Breast
			Neonatal Gynecomastia
			Puberty
			Pubertal Gynecomastia
			Normal Circulating Male Estrogen Concentrations
			Senile Gynecomastia
		Histopathology
		Pathophysiology
			Estrogen Excess
				Testicular Tumors
					Leydig Cell Neoplasms.
					Sertoli Cell Tumors.
					Germ Cell Tumors.
				Adrenal Cortex Neoplasms
				Ectopic Human Chorionic Gonadotropin Production
					Carcinoma of the Lung.
					Hepatocellular Carcinoma.
				Hermaphroditism
					True Hermaphroditism.
					Pseudohermaphroditism.
			Altered Androgen-to-Estrogen Ratio
				Hyperthyroidism
				Liver Cirrhosis
				Recovery From Starvation
			Androgen Deficiency
				Primary Testicular Failure
					Klinefelter Syndrome.
					Hereditary Defects of Androgen Biosynthesis.
				Secondary Testicular Failure
				Androgen Resistance Syndromes
					Reifenstein Syndrome.
					Kennedy Syndrome.
				Increased Aromatase Activity
				Chronic Renal Failure
			Drugs Associated With Gynecomastia
				Known Mechanisms
				Unknown Mechanisms
		Management of Gynecomastia
			Evaluation of Male Breast Enlargement
			Treatment of Male Breast Enlargement
				Medical Therapy
				Surgical Therapy
		Summary
			Gynecomastia in the Pubertal Male
			Gynecomastia in the Aging Male
				Gynecomastia Associated With Prostate Cancer Therapy
		Selected References
		References
	8 Benign, High-Risk, and Premalignant Lesions of the Breast
		Benign Lesions Without Cancer Risk Implications
			Histopathology of Benign Breast Disease
		Epithelial Hyperplasia and Proliferative Breast Disease
			Definition and Background
		Atypical Hyperplasia
		Localized Sclerosing Lesions
			Radial Scar and Complex Sclerosing Lesions
		Duct Ectasia and Fat Necrosis
			Duct Ectasia
			Fat Necrosis
		Fibroadenoma and Phyllodes Tumor
			Fibroadenoma
			Phyllodes Tumor
			Pseudoangiomatous Stromal Hyperplasia
			Papilloma
				Histopathology
			Columnar Cell Lesions
		Selected References
		References
Section IV: Pathology of Malignant Lesions
	9 In Situ Carcinomas of the Breast
		Recent Insights Into the Unique Biology of Ductal Carcinoma in Situ and Lobular Carcinoma in Situ
		Pathology of Ductal Carcinoma in Situ
		Classification of Ductal Carcinoma in Situ
		Extent of Disease
		Extensiveness, Multicentricity, and Multifocality
		Distribution
		Mammographic Correlation
		Margin Status
		Risks of Evolution and Recurrence From Ductal Carcinoma in Situ
		Receptor Proteins, Oncogenes, Tumor Suppressor Genes, and Ploidy
		Special Types of Ductal Carcinoma in Situ With Special Implications
			Hypersecretory Ductal Carcinoma in Situ
			Paget Disease of the Nipple
			Encysted, Noninvasive Papillary Carcinoma
		Pathology of Lobular Carcinoma in Situ
		Acknowledgment
		Selected References
		References
	10 Infiltrating Carcinomas of the Breast
		Molecular Classification
		Histopathologic Classification
		Histologic Types of Invasive Carcinoma
			Invasive Mammary Carcinoma, Not Otherwise Specified
			Invasive Lobular Carcinoma
			Tubular Carcinoma
			Invasive Cribriform Carcinoma
			Mucinous Carcinoma
			Medullary Carcinoma
			Micropapillary Carcinoma
			Secretory Carcinoma
			Salivary Gland–Type Breast Carcinoma
			Adenoid Cystic Carcinoma
			Mucoepidermoid Carcinoma
			Metaplastic Carcinoma
		Prognosis of Invasive Breast Carcinoma
			Tumor Stage
			Histologic Grading
			Additional Elements Occasionally Helpful
		Prognostic Profiles in Breast Cancer
		Predictive Profiles in Breast Cancer
		Conclusion and Shortcomings of the Current System
		Selected References
		References
	11 Mesenchymal Neoplasms and Primary Lymphomas of the Breast
		Mesenchymal Neoplasms of the Breast
			Breast Sarcoma
			Fibroepithelial Neoplasms
				Fibroadenoma
				Phyllodes Tumor
				Mammary Hamartoma
			Fibroblastic and Myofibroblastic Neoplasms
				Fibromatosis
				Myofibroblastoma
				Hemangiopericytoma
				Pseudoangiomatous Stromal Hyperplasia
				Inflammatory Myofibroblastic Tumor
				Malignant Fibrous Histiocytoma
			Vascular Neoplasms
				Hemangioma
				Angiomatosis
				Hemangioendothelioma
				Angiosarcoma and Related Syndromes
			Lipomatous Neoplasms
				Lipoma
				Liposarcoma
			Neural Neoplasms
				Granular Cell Tumor
				Benign Peripheral Nerve Sheath Tumors
					Neurofibroma.
					Schwannoma.
			Myogenic Neoplasms
				Leiomyoma
				Leiomyosarcoma
				Rhabdomyosarcoma
			Osseous Neoplasms
		Primary Breast Lymphoma
			Clinical Features
			Diagnosis and Staging
				Radiologic Features
					Staging.
				Risk Factors/Pathogenesis
				Pathology
				Natural History and Prognosis
				Patterns of Relapse
			Treatment
			Future Directions and Conclusion
		Acknowledgment
		Selected References
		References
	12 Paget Disease of the Breast
		Pathogenesis
		Histopathology
		Clinical Presentation
		Radiologic Findings
		Management
		Prognosis
		Selected References
		References
	13 Primary and Secondary Dermatologic Disorders of the Breast
		Primary Breast Dermatologic Disorders
			Primary Congenital and Developmental Disorders
				Amastia and Athelia
				Hypoplasia and Associated Conditions
				Hyperplasias, Hamartomas and Associated Conditions
				Gynecomastia
			Primary Inflammatory Disorders
				Dermatoses of the Nipple and Breast
					Eczematous Dermatitis (Nummular Eczema).
					Allergic Contact Dermatitis.
					Irritant Contact Dermatitis.
				Dermatoses and Inflammatory Conditions Involving the Dermis
					Mammary Duct Ectasia.
					Radiation Dermatitis.
					Hidradenitis Suppurativa.
					Subareolar Abscess.
					Ruptured Epidermal Inclusion Cyst.
				Dermatoses and Inflammatory Conditions Involving the Subcutaneous Tissue
					Fat Necrosis.
					Panniculitis.
					Mastitis.
						Plasma Cell Mastitis.
						Puerperal/Lactational Mastitis.
						Lymphocytic Mastitis.
						Granulomatous Lobular Mastitis.
						Foreign-Body Mastitis.
				Disorders of Keratinization
					Axillary Granular Parakeratosis.
			Primary Neoplastic Disorders
				Primary Benign Neoplastic Disorders
					Seborrheic Keratosis.
					Lichen Planus–Like Keratosis.
					Benign Cysts and Adnexal Tumors.
					Erosive Adenomatosis of the Nipple.
				Primary Malignant and Neoplastic Disorders
					Paget’s Disease of the Breast.
					Inflammatory Breast Carcinoma.
					Atypical Vascular Lesion.
					Angiosarcoma.
					Malignant Adnexal Tumors.
		Secondary Breast Dermatologic Disorders
			Secondary Inflammatory Disorders
				Infectious Disorders
					Erythrasma.
						Candidiasis.
						Dermatophytosis (Tinea).
						Varicella Zoster Virus.
				Noninfectious Benign Lesions
					Lichen Sclerosis et Atrophicus.
					Seborrheic Dermatitis.
					Psoriasis.
					Drug Hypersensitivity Reactions.
					Coumadin Necrosis.
					Pyoderma Gangrenosum.
					Mondor Disease.
					Granuloma Annulare.
					Acanthosis Nigricans.
					Annular Erythema.
					Sarcoidosis.
					Pityriasis Rosea.
					Lupus Panniculitis.
					Darier Disease.
					Connective Tissue Disorders.
					Body Modification–Associated Dermopathy.
			Secondary Neoplastic Disorders
				Benign Disorders
					Galactoceles.
					Hair Disorders.
					Vascular Neoplasms.
					Smooth Muscle Neoplasms.
					Fibrous Neoplasms.
					Benign Melanocytic Lesions.
				Malignant Disorders
					Actinic Keratosis and Bowen Disease.
					Squamous Cell Carcinoma.
					Basal Cell Carcinoma.
					Malignant Melanoma.
					Dermatofibrosarcoma Protuberans.
					Lymphomas.
					Satellite Skin Metastasis.
		Selected References
		References
	14 Breast Biomarker Immunocytochemistry
		Estrogen Receptor: Historical Perspective
		Progesterone Receptor: Historical Perspective
		Receptor Status Assessment: Why Is It Important?
		Scoring of Receptor Expression
		American Society of Clinical Oncology/College of American Pathologists Recommendations
		Correlation With Oncotype Dx
		Repeat Immunohistochemical Studies on Recurrent and Metastatic Disease
		Commonly Used Monoclonal Antibodies
		Human Epidermal Growth Factor Receptor 2
			Historical Perspective
			Standard Practice and New Challenges
		Ki67 (Proliferation Marker)
		E-Cadherin and p120
		Selected References
		References
Section V: Natural History, Epidemiology, Genetics, and Syndromes of Breast Cancer
	15 Epidemiology of Breast Cancer
		Descriptive Epidemiology
		Differences in Subtypes of Breast Cancer by Race, Ethnicity and Geography
		Sociodemographic Factors
		Traditional Risk Factors for Breast Cancer
			Benign Breast Disease
			Lobular Carcinoma in Situ and Atypical Hyperplasia
			Family History
			Reproductive Factors
		Other Risk Factors for Breast Cancer
			Anthropometry
			Endogenous Hormones
			Dietary Fat and Serum Estradiol
			Estrogen Metabolism
			Diethylstilbestrol Exposure
			Exogenous Hormones: Oral Contraceptives and Postmenopausal Hormone Therapy
			Preeclampsia
			Induced Abortion
			Mammographic Breast Density
				Exogenous Hormones and Mammographic Density
				Dietary Fat and Mammographic Breast Density
			Physical Activity
			Alcohol Consumption
			Smoking
			Bone Mineral Density
			Bisphosphonates
			Night-Shift Work
			Ionizing Radiation
			Summary of Risk Factors for Breast Cancer
		Selected References
		References
	16 Primary Prevention of Breast Cancer
		Identifying Women at Risk
			Breast Cancer Risk Models
			Mammographic Density
			Clinical Risk Counseling
		Chemoprevention
			Tamoxifen
			Raloxifene
		Chemoprevention Risk-Reduction Trials
			Breast Cancer Prevention Trial
				Other Outcomes in the Breast Cancer Prevention Trial
				Other Unfavorable Outcomes in the Breast Cancer Prevention Trial
			International Breast Cancer Intervention Study I
			Summary of the SERM Chemoprevention Trials
		Tamoxifen and Benign Breast Disease
		SERMs in Lobular Carcinoma in Situ and Atypical Hyperplasia
		Overall Risk of Developing Invasive Breast Cancer in Women With Atypical Hyperplasia
		Assessing Risks and Benefits of Tamoxifen for Chemoprevention
		Indications and Contraindications for Risk Reduction With SERMs
		Effect of Tamoxifen in Carriers of Predisposing Genetic Mutations
		Clinical Monitoring of Women Taking Tamoxifen
		Tamoxifen Metabolites
		Clinical Data With Raloxifene
		Study of Tamoxifen and Raloxifene Trial
			STAR Results After 81 Months of Follow-Up
			STAR Trial and Potential Population Impact
		Aromatase Inhibitors
			Anastrozole
			Exemestane
		Expert Recommendations on the Use of Pharmacologic Interventions for Breast Cancer Risk Reduction
			American Society of Clinical Oncology 2013 Clinical Practice Guideline
			US Preventive Services Task Force Recommendations
			National Comprehensive Cancer Network Recommendations
				Tamoxifen Recommendation
				Raloxifene Recommendation
				Aromatase Inhibitor Recommendation
		Summary
		Selected References
		References
	17 Breast Cancer Genetics
		The Value of Genetic Testing
		Role of the Cancer Genetics Counselor
		Identifying Mutation Carriers
		Genetic Testing Technology
			Sanger Sequencing
			Next Generation Sequencing
			Large Rearrangements
		Classifying Variants
		Variants of Uncertain Significance
		Multigene Panels
		Managing Cancer Risk
			Reproductive and Lifestyle Factors
			Enhanced Surveillance
			Chemoprevention
			Risk-Reducing Surgery
				Bilateral Salpingo-Oophorectomy
				Bilateral Prophylactic Mastectomy
		Managing Cancer in Mutation Carriers
			The Syndromes
				BRCA1 and BRCA2
				PALB2
				TP53
				PTEN
				CDH1
				ATM
				CHEK2
				RAD51C
				STK11
				BRIP1
		Selected References
		References
Section VI: Prognostic Factors for Breast Cancer
	18 Clinically Established Prognostic Factors in Breast Cancer
		Nomenclature
		Prognostic Factors
			Axillary Lymph Nodes
			Tumor Size
			Histologic Factors
			Age and Race
		Predictive and Prognostic Factors
			Steroid Receptors
			DNA and Proliferative Markers
			Epidermal Growth Factor Receptor Family
		Summary
		Selected References
		References
	19 Molecular Prognostic Factors for Breast Carcinoma
		Genomic Assays
			Oncotype Dx
			MammaPrint
			Mammostrat
			Prosigna Breast Cancer Prognostic Gene Signature Assay
			Breast Cancer Index
			EndoPredict Test
			Genomic Grade Index
			IHC4
			Nottingham Prognostic Index/NPI+
			MammaTyper
			BreastPRS
			BreastOncPx
		Summary
		Selected References
		References
	20 Risk Factors for Breast Carcinoma in Women With Proliferative Breast Disease
		Nashville Breast Cohort Studies
		Mayo Clinic Studies
		Other Studies
		Extent of Atypical Hyperplasia
		Age, Family History, and Proliferative Disease
		Complex Fibroadenoma and Proliferative Breast Disease
		Effect of Time Since Biopsy on Risk of Breast Cancer
			Radial Scar
			Hormone Replacement Therapy in Women With Proliferative Disease
		Selected References
		References
	21 Steroid Receptors in Breast Cancer
		Estrogen Receptor
			Historical Perspective
			A Current View of the Molecular Mechanism of Estrogen Action
			The Molecular Mechanism of Action of SERMs
			The Molecular Mechanism of Action of SERDs
			The Mechanisms of Drug Resistance to Long-Term Antihormone Therapy
			Estrogen-Induced Apoptosis
				Estrogen-Induced Apoptosis as an Interpretation of the Mortality Decreases After Long-Term Adjuvant Therapy and the WHI
		The Progesterone Receptor
		Androgen Receptor
		Summary and Conclusions
		Selected References
		References
Section VII: Molecular Biology of Breast Carcinogenesis
	22 Molecular Oncology of Breast Cancer
		Hallmarks of Cancer
			Sustaining Proliferative Signaling
			Evading Growth Suppressors
			Resisting Cell Death
			Enabling Replicative Immortality
			Inducing Angiogenesis
			Activation of Invasion and Metastasis
			Genome Instability and Mutation
			Tumor Promoting Inflammation
			Reprogramming Energetics
			Evading Immune Destruction
		Normal Mammary Development and Carcinogenesis
			Endogenous Hormones and Growth Factors
				Prenatal or Fetal
				Postnatal
				Puberty
				Pregnancy and Lactation
				Postmenopausal Involution
				Stem Cells
				Stemness and Clonal Evolution
			Clinical Perspective on Carcinogenesis and Progression
		Molecular Profiling
			Estrogen Receptor
			Progesterone Receptor
			HER2 Membrane Receptor
			Molecular Subtypes of Breast Cancer
				Molecular Subtypes of Triple-Negative Breast Cancers
		Hereditary Breast Cancers
			BRCA1 and BRCA2
				BRCA1
				BRCA2
			PTEN
			CDH1
		Molecular Profiles of Sporadic Breast Cancers
			Genetic Abnormalities in Breast Cancer
				Oncogenes
				Tumor Suppressor Genes
			Driver and Passenger Alterations
			Actionable Alterations
			Common Somatic Mutations
				p53 Tumor Suppressor
			Copy Number Alterations
				HER2
				FGFR1 and FGFR2
			Frequently Altered Molecular Pathways
			Epigenetic Alterations
				Methylation
				Histone Acetylation
				MicroRNAs
			Tumor Microenvironment
				Programmed Cell Death 1 and Programmed Death Ligand 1
				Integrins
				BCL2 and Survivin
		Biomarkers Used in Clinical Management of Breast Cancer
			Markers for the Management of Early Breast Cancers
			Markers for the Management of Advanced/Metastatic Breast Cancers
				Circulating Tumor DNA
		Conclusion
		Acknowledgment
		Selected References
		References
	23 Stem Cells in Breast Development and Cancer
		Stem Cells in the Normal Breast
			Markers of Normal Stem Cells
			Mammary Stem Cell Regulatory Pathways
		Stem Cells in Breast Cancer
			Markers of Cancer Stem Cells
			Key Signaling Pathways of Cancer Stem Cells
			Relationship of Epithelial-Mesenchymal Transition and Cancer Stem Cell States
			Cancer Stem Cells and the Tumor Microenvironment: Clinical Implications
				Cancer Stem Cells and the Immune System
				Cancer Stem Cell–Targeting Therapeutics
		Acknowledgment
		Selected References
		References
	24 Therapeutic Strategies for Breast Cancer
		Epidemiology of Breast Cancer
		Breast Cancer Risk Factors
		The Natural History of Breast Cancer
			Traditional Models for Breast Cancer Natural History
			The Estrogen Paradox
		From Descriptive Models to Biologically Informed Carcinogenesis
			Breast Cancer Initiation
			The Vascular Phase of Tumor Development: The Angiogenic Switch
			Relationship Between Primary Tumor and Breast Cancer Metastases
			Disseminated Tumor Cells
			Tumor Heterogeneity
				Molecular Subtypes of Breast Cancer
				Limitations of Gene Expression Profiling Platforms
				Intrapatient Heterogeneity and Clonal Evolution
		Therapeutic Strategies for the Management of Invasive Breast Cancer
			Surgical Treatment
			Radiation Therapy
			Medical Treatment
				Chemotherapy
					Chemotherapy for TNBC
						Indications.
						Regimens.
					Chemotherapy for HR-Positive/HER2-Negative Breast Cancer
						Indications.
						Regimens.
					Chemotherapy for HER2-Positive Breast Cancer.
				Endocrine Therapy
				Angiogenic Therapy
				Immunotherapy
					Breast Cancer Vaccines.
					Checkpoint Inhibitors.
					Monoclonal Antibodies.
					The Immune-Mediated Effect of Chemotherapy.
		Conclusion and Future Directions
		Selected References
		References
Section VIII: Screening and Diagnosis of Breast Disease
	25 Examination Techniques
		Breast Self-Examination
		Clinical Breast Examination
		Imaging Modalities
		Invasive Diagnostic Procedures
		Selected References
		References
	26 Breast Imaging Screening and Diagnosis
		Mammography
			Screening Mammography
			Diagnostic Mammography
			Standardized Terminology for Mammography Reports
			Normal Mammographic Findings
			Abnormal Mammographic Findings
				Masses
					Benign Masses.
					Malignant Masses.
						Invasive Ductal Carcinoma of No Special Type.
						Invasive Lobular Carcinoma.
						Tubular Carcinoma.
						Medullary Carcinoma.
						Mucinous Carcinoma (Colloid Carcinoma).
						Intracystic Papillary Carcinoma/Invasive Papillary Carcinoma.
						Breast Metastases From Extramammary Malignancies.
						Calcifications.
							Benign Calcifications.
							Malignant Calcifications.
						Ductal Carcinoma in situ.
						Invasive Carcinoma With Extensive Intraductal Component.
				Indirect Signs of Breast Cancer
					Architectural Distortions.
					Asymmetries.
					Abnormal Axillary Lymph Nodes.
		Ultrasound
			Standardized Terminology for Sonography Reports
			Benign Masses
			Malignant Masses
		Magnetic Resonance Imaging
			Standardized Terminology for MRI Reports
			Typically Benign Findings
			Typically Malignant Findings
		Other Breast Imaging Technologies
			Ductography (Galactography)
		Imaging-Guided Interventional Procedures
			Imaging-Guided Core Needle Biopsy
			Imaging-Guided Preoperative Needle Localization
		Staging and Imaging Follow-Up of Women With Breast Cancer
			Evaluation for Distant Metastases
			Follow-Up of the Conservatively Treated Breast
			Follow-Up After Mastectomy
		Selected References
		References
Section IX: Clinical Trials: Biostatistical Applications
	27 Design and Conduct of Clinical Trials for Breast Cancer
		Evolving Ethics and Regulation of Clinical Trials in the United States
		Research Versus Clinical Care
		What Is Not a Clinical Trial
		Why Do Clinical Trials?
		Designing Clinical Trials
		Types of Clinical Trials
			Cohort Trials
				Prospective Cohort Study
				Retrospective Cohort Study
			Cross-Sectional Study Design
			Case-Control Study Design
			Interventional Trials
			Uncontrolled Trials
				Historical Controls
			Controlled Trials
		Trial Design for Phase I Oncology Studies
		Trial Design for Phase II Oncology Studies
			Gehan’s Design
			Fleming’s Design
			Simon’s Optimal Design
			Simon’s Minimax Design
			Comparisons of the Optimal and Minimax Designs
			Fei and Shyr’s Balanced Design
		Trial Design for Phase III Randomized Controlled Studies
		Randomization Process
		Sample Size Determination and Power Analysis
		Monitoring Response Variables
		Judging Quality of Clinical Trials: Level of Evidence
		Reporting of Adverse Events for Clinical Trials
		Conclusions
		Selected References
		Suggested Readings
		References
Section X: Surgery for Benign and Malignant Diseases of the Breast
	28 Indications and Techniques for Biopsy
		Fine-Needle Aspiration Biopsy
			Procedure
			Accuracy
			Cytopathology
		Direct Smear
		Fluid Aspiration
		Core Needle Biopsy
			Ultrasound-Guided Biopsy
			Stereotactic Core Needle Biopsy
			Magnetic Resonance Imaging–Guided Biopsy
		Open Surgical Biopsy
			Choice of Anesthesia
			Wire-Guided Localization
			Intraoperative Ultrasound Guidance
			Radioactive Seed Localization
		Conclusion
		Acknowledgment
		Selected References
		References
	29 General Principles of Mastectomy
		Topographic Surgical Anatomy
			Neurologic Innervation of the Pectoral Muscles
			Vascular Distribution
			Lymphatic Drainage and Routes for Metastases
		Evolution of Surgical Techniques for Mastectomy
		Design of Incisions for Mastectomy in the Treatment of Breast Cancer
			Central and Subareolar Primary Lesions
			Lesions of the Upper Outer or Lower Inner Quadrants
			Lesions of the Upper Inner Quadrants
			Lesions of the Lower Outer Quadrants
			High-Lying (Infraclavicular) Lesions
		Skin-Sparing Mastectomy
			Total Mastectomy With Limited Skin Excision: Rationale and Technique of the “Skin-Sparing” Total Mastectomy
			Factors Affecting Local Recurrence
				Biologic Factors: Effect on Local Recurrence
				Tumor Volume (Size): Effect on Local Recurrence
				Breast Skin Excision: Effect on Local Recurrence
			Evolution of Breast Skin Excision With Mastectomy
				Radical Mastectomy
					Near-Total Excision of the Breast Skin Without Undermining to Develop Skin Flaps.
					Wide Dissection of Skin Flaps With Extensive Skin Removal.
					Wide Dissection of Thin Skin Flaps With Less Extensive Skin Removal.
				Modified Radical Mastectomy
				Skin Preservation Procedures
				Technical Aspects of Skin-Sparing Mastectomy
				Incision Design
				Flap Elevation
				Nipple-Sparing Mastectomy
		Reconstruction Considerations
			Overview of Reconstruction
			Factors Influencing Immediate or Delayed Postmastectomy Reconstruction
			Incisions for Axillary Dissection
		Selected References
		References
	30 Halsted Radical Mastectomy
		Historical Aspects for Development of Radical Mastectomy
		Breast Cancer Treatment in the United States
			Trends and Patterns of Care, 1971 to 1984
			Trends and Patterns of Care, 1985 to 2002 National Cancer Database—American College of Surgeons Commission on Cancer
			Trends in Selection of Mastectomy Therapies, 2000 to 2016
		Indications for Use of the Halsted Radical Mastectomy
		Technique of Radical Mastectomy
		Selected References
		References
	31 Modified Radical Mastectomy and Simple Mastectomy
		Modified Radical Mastectomy
			Historical Evolution of the Surgical Technique
			Retrospective Studies of the Modified Radical Mastectomy
			Prospective Trials for the Modified Radical Mastectomy
		Simple Mastectomy
			Retrospective Studies of the Simple Mastectomy
			Evolution of Simple Mastectomy With Sentinel Lymph Node Biopsy
			Prospective Trials for the Simple Mastectomy With and Without Irradiation
			Contralateral Prophylactic Mastectomy
			Prophylactic Simple Mastectomy in High-Risk Patients
			Role of Surgical Excision of Primary Tumor in Patients With Stage IV Disease
		Modified Radical Mastectomy Technique
			Anesthesia and Positioning
			Sterile Skin Preparation
			Skin Incision and Skin Flap Development
			Removal of Breast
			Operative Techniques for Variations of Simple Mastectomy
			Dissection of Axillary Lymph Nodes
			Closure
			Postoperative Care
		Selected References
		References
	32 Breast Conservation Therapy for Invasive Breast Cancer
		Historical Perspective
		Survival
		Local Recurrence
		Cosmetic Outcome
		Patient Selection
		Magnetic Resonance Imaging
		Operative Technique
			Localization
			Incision
			Tumor Removal
			Quadrantectomy
			Oncoplastic Surgery
			Evaluation of Margins
			Closure
			Reexcision
		Axilla
		Radiation Therapy
			Radiation and Its Role in Breast Conservation
			Radiation Therapy Versus No Radiation Therapy
			Radiation Therapy Sequencing
			Radiation Therapy Technique
			Radiation Dose: The Use of a Tumor Bed Boost
			Length of Radiation Treatment
		Selected References
		References
Section XI: Breast Reconstruction
	33 Breast Reconstruction and Oncoplastic Surgery
		Role of Reconstruction in Breast Cancer Treatment
		Definition of the Mastectomy Deformity
			Mastectomy
			Partial Mastectomy/Lumpectomy
		Reconstructive Surgical Methods
			Tissue Expansion/Implants
			Reconstruction With Acellular Dermal Matrix
				Surgical Technique for Tissue Expander/Acellular Dermal Matrix
			Myocutaneous Flaps
				Surgical Technique of the Latissimus Flap
				Surgical Technique of the Thoracoepigastric Flap
				Surgical Technique of the Abdominal Transverse Rectus Abdominis Myocutaneous Flap
			Oncoplastic Surgery
			Reconstruction With Fat Grafting
			Opposite Breast Considerations
				Reduction Mammaplasty
				Augmentation Mammaplasty
			Nipple Reconstruction
			Reconstruction Postradiation
			Timing of Breast Reconstruction
		Conclusions
		Selected References
		References
Section XII: Complications of Breast Surgery
	34 Wound Care and Complications of Mastectomy
		Care of the Postmastectomy Wound
		Complications of Mastectomy
			Lymphedema
			Wound Infection
			Seroma
			Pneumothorax
			Tissue Necrosis
			Hemorrhage
			Injury to Neurovascular Structures
			Deep Venous Thrombosis
			Postmastectomy Pain Syndrome
		Selected References
		References
	35 Quality Measures and Outcomes for Breast Cancer Surgery
		Why Measure Quality?
		Who Are the Stakeholders for Quality Measurement?
		What Is the American History of Surgical Quality Measurement?
		What Are Quality and Value?
		What Are Safety in Surgery and Diagnostic Errors?
		How Do We Identify a Gap in the Quality of Care?
		Where Are the Databases for Quality and Clinical Outcomes Research?
		How Do We Measure Quality?
		What Is a Quality Measure, and Where Do We Find Them?
		What Are the Quality Reporting Systems in the Public Sector?
		What Is the Future of Public Quality Measurement Reporting?
		How Do We Create the Best Quality Measures?
		How Do We Rank a List of Many Quality Measures?
		How Are Quality Measures Used?
		How Do We Analyze Quality Data and Provide Fair Peer Comparisons?
		What Is a Benchmark?
		How Do We Improve Quality?
		Do Quality Measurement and Improvement Programs Work?
		Have the Breast-Specific Quality Measurement Programs Improved Breast Care?
		What Are the Risks of Quality Measurement?
		What Are the Future Challenges in Quality Measurement?
		Conclusion
		Selected References
		References
	36 Lymphedema in the Postmastectomy Patient
		History
		Anatomy
			Lymph Nodes and Lymphatics Draining the Upper Extremity
		Pathophysiology
		Etiologic Risk Factors and Incidence
			Incidence
		Lymphedema From Radiation Treatment
		Classification
		Patient History and Measurement of Lymphedema
		Nonoperative Management of Lymphedema
			Complete Decongestive Physiotherapy
			Exercise
			Hyperbaric Oxygen
			Benzopyrones
		Prevention of Lymphedema
			Sentinel Lymph Node
		Nonoperative Management of the Axilla
		Axillary Reverse Mapping and Reanatomosis
			Axillary Reverse Mapping
			LYMPHA (Lymphedema Microsurgical Preventive Healing Approach)
		Operative Management of Lymphedema
			Excisional Procedures
			Tissue Transfer for Refractory Lymphedema
			Liposuction
			Lymphovenous Shunts
			Postmastectomy Pain Syndrome
		Lymphangiosarcoma: a Rare but Fatal Complication of Long-Standing Lymphedema
		Summary
		Acknowledgment
		Selected References
		References
Section XIII: Current Concepts and Management of Early Breast Carcinoma (Tis, Tmic, T1)
	37 Assessment and Designation of Breast Cancer Stage
		Staging: Past, Present, and Future
		Clinical, Pathologic, and Biological Markers and Factors in Determining Prognosis
			Clinical Factors
			Primary Tumor Characteristics
				Tumor Size
				Tumor Location
				Tumor Histology
				Tumor Grade
				Histopathologic Features of Tumor
				Estrogen and Progesterone Receptors
				HER2/neu Expression
				Tumor Growth Rate and Proliferation
			Biological Markers
			Lymph Node Status
				Axillary Nodal Disease
				Sentinel Lymph Node Mapping
				Internal Mammary Nodal Disease
				Supraclavicular Nodal Disease
				Intramammary Nodal Disease
				Pathologic Assessment of Lymph Nodes
		Evolution of Staging Systems
		Current Staging System
			Specific Stages
				T Stage (Tumor Size)
				N Stage
				M Stage
			Stage Groupings
			Histopathlogic Grade
		Extent and Multicentricity of In Situ and Invasive Carcinoma
			Case Studies
				Case 1
				Case 2
				Case 3
				Case 4
				Case 5
			Biological Studies
		Associated Factors
			Clinical Follow-Up Studies
		Clinical Implications of Multicentricity
		Acknowledgment
		Selected References
		References
	38 Lobular Carcinoma in Situ of the Breast
		Historical Background
			LCIS as a Premalignant Lesion
			LCIS as a Risk Factor for Invasive Breast Cancer and Lobular Neoplasia
			Continued Definition of LCIS as a Unique Stage 0 Preinvasive “Cancer”
		LCIS Histopathology
			Morphologic Features of LCIS
			Pleomorphic LCIS
			Immunohistologic Features and Molecular Genetics of LCIS
		Clinical Presentation, Natural History, and Biologic Significance of LCIS
			Clinical Features of LCIS
			Risk of Subsequent Invasive Carcinoma After LCIS Diagnosis
		Female Steroid Hormones and LCIS
			Changing Incidence Rates of LCIS and the Influence or Exogenous Hormones on Lobular Carcinogenesis
		Endocrine Chemoprevention for LCIS
			Chemoprevention of Invasive Breast Cancer
			Aromatase Inhibitors for Chemoprevention
		Surgical Intervention for LCIS
			Surgical Excisional Biopsy Showing LCIS
			Core Needle Samples Showing LCIS
			The Use of Breast Magnetic Resonance Imaging for Lobular Neoplasia
			Breast Conservation in Patients Who Have LCIS Coincident With Invasive Cancer
			Is There a Defined Role for Surgical Prophylaxis With LCIS?
		Conclusions
		Selected References
		References
	39 Ductal Carcinoma in Situ of the Breast
		The Changing Nature of Ductal Carcinoma in Situ
		Pathology
			Classification
			Progression to Invasive Breast Cancer
			Immunohistochemical and Molecular Phenotypes in DCIS
			Microinvasion
			Multicentricity and Multifocality of Ductal Carcinoma in Situ
		Detection and Diagnosis
			Biopsy Techniques
		Treatment
			Treatment End Points for Patients With Ductal Carcinoma in Situ
			Treatment Options
				Mastectomy
				Breast Conservation
				Are We Overtreating Ductal Carcinoma in Situ?
				Intraoperative Radiation Therapy for Ductal Carcinoma in Situ
				Reasons to Consider Excision Alone
					Common Use.
					Anatomic.
					Biological.
					Pathology Errors.
					Prospective Randomized Data.
					Radiotherapy May Cause Harm.
					Socioeconomic.
					Increased Risk.
					Only One Time.
					Improved Patient Selection.
					NCCN Guidelines.
		Prospective Randomized Ductal Carcinoma in Situ Trials
		Tamoxifen for Ductal Carcinoma in Situ
		Determination of HER2/neu Status and Potential Benefit of Neoadjuvant Trastuzumab
		Predicting Local Recurrence in Conservatively Treated Patients With DCIS
			Treatment Selection for Patients With DCIS of the Breast Using the University of Southern California/Van Nuys Prognostic Index
				Pathologic Evaluation
				Statistical Analysis
				Results
				Discussion of Using USC/VNPI to Select Treatment
			Using the USC/VNPI for Patients Undergoing Mastectomy
		Oncotype DX Breast DCIS Score
		Sentinel Node Biopsy for Ductal Carcinoma in Situ
		Summary
		Selected References
		References
	40 The New Paradigm
		General Considerations
			Leading the Oncoplastic Team
			Rationale for Oncoplastic Breast Surgery
			Reconstructive Goals
		Preoperative Planning
		Surgical Considerations
		Oncoplastic Techniques
			Simple Glandular Flap Techniques
			Crescent, Hemibatwing, and Batwing Techniques
			Vertical Mammaplasty, Inframammary Excision, and Central Excision Techniques
			Round Block Mastopexy (Benelli) and Reduction Mammaplasty Techniques
		Extreme Oncoplasty
		Summary
		Selected References
		References
	41 Therapeutic Value of Axillary Node Dissection and Selective Management of the Axilla in Small Breast Cancers
		Lymphatic Function and Nodal Metastases
		Axillary Anatomy and Evaluation
		Axillary Radiotherapy
		Therapeutic Role of Axillary Node Dissection
		Selective Management of Axilla
		Targeted Axillary Lymph Node Dissection
		Selected References
		References
	42 Lymphatic Mapping and Sentinel Lymphadenectomy for Breast Cancer
		History of Sentinel Node Concept in Breast Cancer
		Evolution of Dye-Directed Sentinel Lymphadenectomy for Breast Cancer
			Surgical Feasibility
			Histopathologic Staging
			Prospective Validation
		Complete Nonsentinel Node Staging and Proof of Principle
		Prospective Study of Sentinel Lymphadenectomy Alone for a Tumor-Free Sentinel Node
		Identification of the Sentinel Node in Breast Cancer by Radiolocalization
		Identification of the Sentinel Node With Preoperative Lymphoscintigraphy and Intraoperative Radioguided Surgery
		Combined Technique of Vital Dye and Radioisotope
		Global Experience With Sentinel Lymphadenectomy in Breast Cancer
			Definition of the Sentinel Node
		Multicenter Lymphatic Mapping Trials
		Clinical, Pathologic, and Technical Aspects of Sentinel Lymphadenectomy
			Patient Selection Criteria
				Age
				Gender
				Body Habitus
				Pregnancy and Lactation
				Previous Breast or Axillary Surgery
				Previous Excision
			Tumor Features
				Type of Carcinoma
					Invasive Carcinoma.
					Ductal Carcinoma In Situ and Ductal Carcinoma In Situ With Microinvasion.
				Feasibility of Sentinel Lymph Node Dissection for Palpable Versus Nonpalpable Tumors
				Multifocal or Multicentric Disease
				Palpable Axillary Lymph Nodes
			Applications of Sentinel Lymphadenectomy
				Sentinel Lymphadenectomy and Operative Procedure
				Preoperative Chemotherapy
				Management of the Internal Mammary Lymph Sentinel Node
			Predictors of Sentinel Node Metastases
				Tumor Size and Risk of Sentinel Node Metastases
				Number of Sentinel Nodes Removed
				Significance of Micrometastases
				Management of the Axilla When the Sentinel Node Is H&E Positive
				Radiation Treatment of the Axilla
		Technical Considerations
			General Technical Considerations
			Lymphatic Mapping With Vital Dye
				Selection of Optimal Dye for Intraoperative Lymphatic Mapping
				Complications of Dye Injection
				Anesthetic Considerations
				Vital Dye Injection Technique
				Dissection Technique
		Radiolocalization and Lymphatic Mapping With Isotopes
			Radiopharmaceutical
			Effect of Isotope Filtration on Dose and Volume of Injectate
			Injection Site
			Timing of Injection, Lymphoscintigraphy, Intraoperative Gamma-Probe Detection
			Surgical Technique for Radioguided Sentinel Lymphadenectomy
			Hottest Node
			Pearls to Remember for the Combined Technique
		Histopathologic Evaluation
			False-Negative Sentinel Nodes
			Predictors of Nonsentinel Node Metastases
		Morbidity of Sentinel Lymphadenectomy
		Learning Curve
			Guidelines
		Prospective Randomized Clinical Trials
			NSABP B-32
			ACOSOG Z0010
			ACOSOG Z0011
			ALMANAC
			AMAROS Trial
		Summary
		Selected References
		References
	43 Detection and Significance of Axillary Lymph Node Micrometastases
		Definition and Classification of Axillary Lymph Node Micrometastases
			Prognostic Significance of Axillary Lymph Node Micrometastases: Retrospective Data
			Classification by Size of Axillary Lymph Node Metastasis
			Classification by Frequency of Occult Axillary Lymph Node Metastases
		The Ludwig Studies of Axillary Lymph Node Micrometastases
		Logistical Hurdles in the Detection of Axillary Lymph Node Micrometastases
		Role of Enhanced Pathology in Sentinel Lymph Node Biopsy
			Improved Axillary Lymph Node Staging
			Validation of the Sentinel Lymph Node Hypothesis
			Reduction in the Rate of False-Negative Sentinel Lymph Node Biopsy
			Risk of Nonsentinel Lymph Node Metastasis in Micrometastatic Sentinel Lymph Node–Positive Patients
		Prognostic Significance of IHC-Detected Micrometastases: Prospective Studies
			American College of Surgeons Oncology Group Z0010 Trial
			National Surgical Adjuvant Breast and Bowel Project B-32 Trial
		Surgery for SLN Micrometastases: A Shifting Paradigm
		Unresolved Controversies
			Are Immunohistochemistry-Positive Cells Metastases or Displacement Artifacts?
			Can Pathologic Evaluation of SLNs Be Standardized?
		Conclusions and Future Directions
		Selected References
		References
	44 Intraoperative Evaluation of Surgical Margins in Breast Conserving Therapy
		Frequency of Margin-Positive Partial Mastectomy
		Pathologic Assessment of Margin Status and Specimen Handling
			Gross Intraoperative Inspection of Tumor Margins
			Cavity Shave Margin Technique
			Frozen Section Analysis
			Intraoperative Cytologic Evaluation by Touch Preparation
			Intraoperative Ultrasound
			Intraoperative Specimen Radiography
			Other Approaches and Emerging Technology for Margin Analysis
		Summary and Conclusions
		Selected References
		References
	45 Surgical Management of Early Breast Cancer
		Preoperative Evaluation
		Surgical Options for Early Breast Cancer
		Breast Conservation Surgery
		Mastectomy
		Axillary Evaluation
		Adjuvant Radiotherapy
		Outcome After Surgical Management of Breast Cancer
			Management of the Elderly Patient
			Invasive Lobular Breast Cancer
			Family History of Breast Cancer
		Minimally Invasive Ablative Therapies
		Radiofrequency Ablation
		Cryoablation
		Interstitial Laser Therapy
		Microwave Ablation
			High-Intensity Focused Ultrasound Ablation
		Irreversible Electroporation
		Summary
		Selected References
		References
Section XIV: Therapy for Stages 0, I, and II Breast Cancer
	46 Biological Basis of Radiotherapy of the Breast
		Radiotherapy Techniques: Introduction
		Radiation Therapy Modalities: External Beam Versus Brachytherapy
		Radiobiological Considerations
		Anatomic Considerations for Radiation Delivery
		External-Beam Techniques and Considerations
			Standard Treatment Field Setup
			Two-Dimensional Versus Three-Dimensional Conformal Versus Intensity-Modulated Radiation Therapy
			Patient Positioning
			Image-Guided Radiation Therapy (IGRT)
			Boost Treatment Planning
		Cardiac Avoidance in Breast Radiotherapy Planning
			The Role of the Surgeon
			Heart Blocks
			Patient Positioning
				Supine Breast Board
				Prone Breast Board
			Deep Inspiration Breathing Techniques
			Accelerated Partial Breast Irradiation
			Hypofractionation
			3D Planning
			Protons
		Accelerated Partial Breast Irradiation
			Techniques for Delivery of APBI
				External Beam/3D Conformal Radiation Therapy
				Brachytherapy
					Interstitial Brachytherapy.
					Intracavitary Brachytherapy Balloon-Based Brachytherapy.
					Intraoperative Photon/Electron Radiotherapy.
		Conclusions
		Selected References
		References
	47 Radiotherapy and Ductal Carcinoma in Situ
		Randomized Trials Demonstrate Efficacy of Radiotherapy for Treatment of DCIS
		Results With Excision Alone in Selected Patients
		Factors Associated With Local Recurrence
			Clinical Factors
				Patient Factors
				Pathologic Factors
				Imaging Factors
		Tools to Predict Risk
		Tamoxifen and Radiotherapy
		Radiation Treatment Techniques
		Patterns of Recurrence and Results of Salvage Treatment
		Radiation Therapy After Mastectomy
		Conclusions
		Selected References
		References
	48 Radiotherapy and Regional Nodes
		Patient Selection
			Positive Sentinel Node Without a Completion Axillary Dissection
			Positive Sentinel Node and Completion Axillary Dissection With a Total of One to Three Positive Nodes
		Radiotherapy Techniques for Regional Nodes
			3D Conformal Radiation
			Multifield IMRT
			Proton Therapy
		Selected References
		References
	49 Postmastectomy Radiotherapy
		Randomized Trials of Postmastectomy Radiotherapy
		Controversies Surrounding Application of Randomized Trial Data in N1 Disease
		Special Considerations
			Patients With Node-Positive Disease and Undissected Axillae After Sentinel Lymph Node Biopsy
			Postmastectomy Radiotherapy in Node-Negative Breast Cancer
			Postmastectomy Radiotherapy in Patients Treated With Neoadjuvant Chemotherapy
		Tumor Biology Considerations
		Postmastectomy Radiotherapy and Reconstructive Surgery
		Conclusions
		Selected References
		References
	50 Breast Conserving Therapy for Invasive Breast Cancers
		Randomized Trials Comparing Breast Conserving Surgery and Radiation Therapy With Mastectomy
		Patient Selection for Breast Conserving Surgery and Radiation
			Clinical Factors
				Patient Age
				Tumor Size
				Gross Multifocal/Multicentric Disease
				Genetic Factors
				Race
			Pathologic Factors
				Margin Status
				Tumor Subtyping
				Other Pathologic Factors
			Treatment Factors
				Surgery
				Radiation Boost
				Adjuvant Systemic Therapy
		Patient Selection Factors for Hypofractionated Whole Breast Irradiation
		Timing of Radiation Therapy in Relation to Surgery and Systemic Therapy
		Characteristics and Management of Local Failure After Breast Conserving Surgery and Radiation Therapy
		Breast-Conserving Surgery Without Radiation Therapy
		Conclusions
		Selected References
		References
	51 Partial Breast Irradiation
		Accelerated Partial Breast Irradiation
			Interstitial Accelerated Partial Breast Irradiation
			Applicator Accelerated Partial Breast Irradiation
			External-Beam Accelerated Partial Breast Irradiation
			Expert Consensus Statements
			Future Directions
		Intraoperative Radiation Therapy
			Randomized Studies
			Additional Studies
			Boost
			Future Directions
		Conclusions
		Selected References
		References
	52 Radiation Complications and Their Management
		Fatigue and Myelosuppression
		Radiation Dermatitis and Infections
		Cosmesis and Breast-Related Symptoms
		Rib Fracture
		Brachial Plexopathy
		Pulmonary Complications
		Cardiac Complications
		Second Malignancies
		Complications in Patients With Collagen Vascular Disease
		Conclusions
		Selected References
		References
	53 Radiation Therapy for Locally Advanced Breast Cancer
		Definition
		Incidence
		Outcomes
		General Treatment Paradigms
		Rationale for Use of Systemic Therapy
		Rationale for Postmastectomy Radiation
		Locoregional Recurrence Rates Without PMRT
		Guideline Statements for PMRT and LABC
		Studies for LABC
		RT Alone for Operable LABC
		Neoadjuvant Chemotherapy Followed by Either Resection or Radiation
		Resection Followed by Systemic Therapy and Either Observation or Radiation
		Neoadjuvant Systemic Therapy and Radiation for LABC
		Inoperable LABC
		Inflammatory Breast Carcinoma
		Role for PMRT After NAC and Mastectomy
		Potential Option for BCS After NAC for LABC
		Locoregional Recurrence Risk on NSABP Trials of NAC and Implications for RT
		Other Prognostic Factors and Future Directions
		Locoregional Radiation Targets and Techniques for LABC
		Conclusion
		Selected References
		References
	54 Adjuvant Endocrine Therapy
		Rationale for Adjuvant Endocrine Therapy
		Who Is a Candidate for Adjuvant Endocrine Therapy?
		Adjuvant Endocrine Therapy: Mechanism of Action
			Selective Estrogen Receptor Modulators
			Aromatase Inhibitors
			Ovarian Ablation and Ovarian Function Suppression
		Approaches to Adjuvant Endocrine Therapy for Invasive Early-Stage Breast Cancer
			Evaluating Menopausal Status
			Options for Postmenopausal Women With Invasive Early-Stage Breast Cancer
				Tamoxifen Monotherapy for 5 Years: The Historical Standard
				Tamoxifen Monotherapy for 10 Years
				Aromatase Inhibitor Therapy for 5 Years
				Sequential Therapy With Tamoxifen and an Aromatase Inhibitor (or Vice Versa) for 5 Years Total
				Tamoxifen for 5 Years Followed by an Aromatase Inhibitor for Up to 10 Years Total
				Aromatase Inhibitor for Longer Than 5 Years
				Selecting an Adjuvant Endocrine Therapy Regimen for Postmenopausal Women With Early-Stage Invasive Hormone Receptor–Positive Breast Cancer
			Options for Premenopausal Women With Invasive Early-Stage Breast Cancer
				Tamoxifen Monotherapy for 5 Years
				Tamoxifen Monotherapy for 10 Years
				Tamoxifen for 5 Years Followed by an Aromatase Inhibitor for 5 Years
				Ovarian Ablation or Ovarian Function Suppression Plus Tamoxifen or an Aromatase Inhibitor
				Selecting an Adjuvant Endocrine Therapy Regimen for Premenopausal Women With Early-Stage Invasive Hormone Receptor–Positive Breast Cancer
				Fertility Considerations in Premenopausal Women With Early-Stage Invasive Breast Cancer Undergoing Adjuvant Endocrine Therapy
		Timing of Initiation of Adjuvant Endocrine Therapy
		Moving Beyond Hormone Receptor Status: Biomarkers to Guide Therapeutic Decisions in Women With Invasive Early-Stage Hormone Receptor–Positive Breast Cancer
			Estimating the Risk of Recurrence in Women Treated With Adjuvant Endocrine Therapy
			Determining the Duration of Therapy: Biomarkers for Late Recurrence
			Determining the Type of Endocrine Therapy: Biomarkers Suggestive of Benefit From Tamoxifen or Aromatase Inhibitor Therapy
		Approaches to Adjuvant Endocrine Therapy for Ductal Carcinoma in Situ
		Common Side Effects of Adjuvant Endocrine Therapy
			Menopausal Symptoms
			Sexual Dysfunction
			Uterine Disorders
			Thromboembolism
			Cardiovascular Disorders
			Mood Disturbances
			Bone and Joint Pain
			Loss of Bone Mineral Density, Osteoporosis, and Fractures
			Quality of Life
		Adherence to Adjuvant Endocrine Therapy
		Conclusion
		Selected References
		References
	55 Adjuvant and Neoadjuvant Systemic Therapies for Early-Stage Breast Cancer
		Guidance in a Changing Landscape: St. Gallen and the National Comprehensive Cancer Network
		Biology Defining Therapy: Breast Cancer Subtypes
		Adjuvant Chemotherapy
		First-Generation Regimens
			Introduction of Anthracyclines
			Addition of Taxanes to Anthracycline-Based Chemotherapy
			Dose Density
			Non–Anthracycline-Containing Regimens
			Bone Marrow Transplant
		ER-Positive Disease
			Considering Chemotherapy
				Genomic Profiling for Risk Stratification
				When to Consider Chemotherapy for ER-Positive Disease
			Tamoxifen
			Aromatase Inhibitors
			Ovarian Suppression
			Optimal Endocrine Therapy for Pre- and Postmenopausal Women
		Bisphosphonates in ER-Positive Breast Cancer
		HER2-Positive Disease
			Trastuzumab
				Duration of Therapy
				Deescalation of Therapy: Small HER2-Positive Tumors
			Pertuzumab
		Neoadjuvant Therapy
			Advantages
			Limitations
			Breast and Axillary Assessments
			Pathologic Complete Response
		Selected References
		References
	56 HER2-Positive Breast Cancer
		HER2 Biology
		HER2 Pathology
		HER2-Targeted Therapy
			HER2 Metastatic Therapy
			HER2 Adjuvant Therapy
				Duration of Adjuvant Trastuzumab
				Predictors of Response to Adjuvant Trastuzumab
				Role of HER2 Variants
				Role of Adjuvant Trastuzumab in Small, Lymph Node–Negative Tumors
		Future Directions in HER2-Targeted Therapy
		Selected References
		References
	57 Bisphosphonates in Early Breast Cancer
		Bisphosphonates: Mechanism of Action
		Types of Bisphosphonates
		Rationale for an Anticancer Effect for Bisphosphonates
		Clinical Trials on Adjuvant Bisphosphonates in Breast Cancer
			Trials Using Clodronate
			Trials Using Ibandronate
			Trials Using Zoledronate
		Individual Patient-Level Data Meta-Analysis
		Rationale for Bisphosphonate Benefit in Postmenopausal Women
		Safety of Adjuvant Bisphosphonates
		When to Consider Adjuvant Bisphosphonates
		Conclusions
		Selected References
		References
	58 Oncofertility Options for Young Women With Breast Cancer
		Oogenesis and Assessing Ovarian Reserve
			Oogenesis
			Assessing Ovarian Reserve
		Gonadotoxicity of Cancer Therapies in Reproductive-Age Women
			Surgery of the Breast
			Impact of Radiation on Fertility
			Chemotherapy in the Breast Cancer Setting
			Biological Agents Used in the Treatment of Breast Cancer
			Endocrine Therapy Used in the Treatment of Breast Cancer
		Fertility Preservation Options
			Oocyte or Embryo Cryopreservation
			Ovarian Tissue Cryopreservation and Transplantation
			Mitigating the Risk: The Role of Ovarian Transposition and Medical Suppression
		Contraception and Cancer Therapy
		Female Sexuality After Cancer Therapy
		Pregnancy in Cancer Patients and Survivors
		Talking With Patients and Families About Future Fertility
		Oncofertility in Clinical Practice
		Acknowledgment
		Selected References
		References
Section XV: Management of Advanced, Local, Regional, and Systemic Disease
	59 Surgical Procedures for Advanced Local and Regional Malignancies of the Breast
		Staging System Revisions and Implications
		Pretreatment Evaluation, Diagnosis, and Management
		Unimodal Treatment Approaches
			Surgery
			Radiotherapy
		Multimodal Approaches
			Early Trials
			Chemotherapy
			Endocrine Therapy
			Targeted Therapy
			Adjuvant Radiotherapy
		Breast Conserving Surgery in Locally Advanced Breast Cancer
		Axillary Staging
			Axillary Lymphadenectomy
				Rationale
				Technique
			Role of Sentinel Lymph Node Biopsy
		Timing of Therapies
		Full-Thickness Chest Wall Resection Revisited
		Reconstructive Techniques
			Timing of Breast Reconstruction
				Immediate Reconstruction
				Delayed Reconstruction
		Options for Chest Wall Closure
			Skin Grafts
			Myocutaneous Flaps
				Latissimus Dorsi Musculocutaneous Flap
			Rectus Abdominis Transposition and Free Flaps
			Vertical Rectus Abdominis Myocutaneous Flap
			Transverse Rectus Abdominis Myocutaneous Flap
				Pedicled
				Free Rectus Musculocutaneous Flaps
			Microvascular Composite Tissue Transplantation (Free Flaps)
				Deep and Superficial Inferior Epigastric Artery Perforator Flaps
			Pectoralis Major Flap
			External Oblique Flap
			Fasciocutaneous Flaps
			Cutaneous and Local Flaps
			Omental Flaps
		Full-Thickness Chest Wall Defects and Prosthetic Materials
		Radiotherapy and Reconstruction
		Multidisciplinary Approach
		Algorithm for Chest Wall Reconstruction
		Selected References
		References
	60 Solitary Metastases
		Liver
		Lung
		Bone
		Brain
		Summary
		Selected References
		References
	61 Locoregional Recurrence After Mastectomy
		Definitions
		Incidence
			Chest Wall Recurrences
			Nodal Recurrences
			Prior Radiation Therapy
			Prior Systemic Therapy
			Prior Neoadjuvant Chemotherapy
			Genomic Characterization
		Detection and Diagnosis
		Survival After Locoregional Recurrence
		Local Treatment
		Radiation Therapy
		Systemic Therapy
		Conclusion
		Selected References
		References
	62 Principles of Preoperative Therapy for Operable Breast Cancer
		Coming of Age for Preoperative Systemic Therapy in Operable Breast Cancer
		Rationale for Preoperative Systemic Therapy
		Patient Selection for Preoperative Therapy in Operable Breast Cancer
		Delivery of Optimal Preoperative Systemic Therapy
			Preoperative Chemotherapy
			Response-Adapted Preoperative Chemotherapy
			Endocrine Therapy
			On Treatment Monitoring and Posttreatment Management
		Conclusions
		Selected References
		References
	63 Locally Advanced Breast Cancer
		Epidemiology
		Survival
		Diagnosis and Staging
		Prognostic Factors
		Evolution of Local Therapy
		Combined Modality Treatment
		Neoadjuvant Chemotherapy
		Neoadjuvant Anti-HER2-Based Therapy
		Neoadjuvant Antiestrogen Therapy
		Assessment of Response to Neoadjuvant Chemotherapy
		Predictors of Response to Neoadjuvant Therapy
		Breast Conserving Surgery
		Management of the Axilla: Historical Perspective and Current Recommendations
			Management of the Axilla in Node-Negative Patients
			Management of the Axilla in Node-Positive Patients
			Management of the Axilla in Patients Undergoing Neoadjuvant Therapy
		Treatment Summary
		Selected References
		References
	64 Inflammatory Breast Cancer
		Introduction and Historical Backdrop
		Epidemiology
		Diagnosis
			Clinical Presentation
			Imaging
			Pathology
		Medical Management and Trials
			Postneoadjuvant/Adjuvant Strategies
		Surgical Management
		Radiation Management
		Metastatic Disease
			New Directions
		Conclusion
		Selected References
		References
	65 Neoadjuvant Chemotherapy and Radiotherapy
		Molecular Subtypes of Breast Cancer and Response to Neoadjuvant Chemotherapy
		Eligibility for Neoadjuvant Chemotherapy or Neoadjuvant Radiation Therapy
		Evaluation of Candidates for Neoadjuvant Chemotherapy or Neoadjuvant Radiation Therapy
		Outcomes and End Points of Neoadjuvant Therapy
		Neoadjuvant Chemotherapy by Breast Cancer Subtypes
		Targeted Therapy
			Anti-HER2 Therapy
		Antiangiogenic Therapy
		Neoadjuvant Radiation Therapy for Breast Cancer
		Response Assessment After Neoadjuvant Chemotherapy
		Surgical Management After Neoadjuvant Chemotherapy
		Staging the Axilla and Sentinel Lymph Node Procedure
		Chemotherapy After Surgery
		Radiation Therapy After Neoadjuvant Systemic Therapy
		The Neoadjuvant Setting for Research and Drug Development
		Conclusion and Future Directions
		Selected References
		References
	66 Detection and Clinical Implications of Occult Systemic Micrometastatic Breast Cancer
		Gene Expression Profiling of Breast Cancer Cells
		Cancer Stem Cells
		Methods for Analysis of CTCs
			CTC Enrichment
				Physical Properties
				Biological Properties
			CTC Detection
				Protein-Based Strategies
				Nucleic Acid–Based Strategies
		Clinical Applications of CTCs
			Metastatic Breast Cancer
			Early Breast Cancer
		Role of CTCs as a “Liquid Biopsy” in Metastatic Disease
		Conclusions and Future Directions
		Selected References
		References
	67 Management of the Intact Breast Primary in the Setting of Metastatic Disease
		Retrospective Analyses of Primary Site Local Therapy
			Surgical Resection of the Primary Tumor and Survival
			Radiotherapy for the Primary Tumor and Survival
			Effect of Primary Site Local Therapy on Locoregional Control
			Retrospective Studies Questioning the Benefit of Primary Site Local Therapy in De Novo Stage IV Breast Cancer
			Selection Biases in the Retrospective Analyses
		Randomized Prospective Trials
			Trials Requiring Induction Systemic Therapy
			Trials Requiring Randomization to Locoregional Therapy Before Systemic Therapy
			Prospective Registry Trial of de Novo Stage IV Breast Cancer Patients
		Who Should Be Offered Locoregional Therapy
		Conclusion
		Selected References
		References
	68 Management of Bone Metastases in Breast Cancer
		Pathophysiology
		Clinical Presentation
		Diagnosis
		Surgical Management
			Prophylactic Surgery
			Pathologic Fractures
		Radiotherapy
			Radiotherapy Alone
			Postoperative Radiotherapy
			Side Effects
			Retreatment With Radiotherapy
			Radiopharmaceuticals
		Systemic Osteoclast Inhibitors
			Bisphosphonates
			Denosumab
		New Treatment Modalities
		Conclusions and Recommendations
		Acknowledgment
		Selected References
		References
	69 Chemotherapy and HER2-Directed Therapy for Metastatic Breast Cancer
		Epidemiology
		Therapeutic Goals
		Prognostication
		Medical Evaluation in the Metastatic Setting
		Local Therapy for Metastatic Breast Cancer
			Breast Surgery in Patients With Metastatic Disease
		Selecting Therapy for Metastatic Breast Cancer
			Selecting a First-Line Regimen in HER2-Negative Metastatic Breast Cancer
			Single-Agent Versus Combination Chemotherapy in HER2-Negative Breast Cancer
		Chemotherapy for Metastatic Breast Cancer
			Anthracyclines
			Taxanes
			Alkylating Agents
			Antimetabolites
				Fluoropyrimidines
				Gemcitabine
			Other Microtubule Inhibitors
			Vinca Alkaloids
			Treatment of HER2-Positive Metastatic Breast Cancer
			Brain Metastases in HER2-Positive Breast Cancer
		Novel Agents in Metastatic Breast Cancer
		Historical Treatments for Metastatic Breast Cancer
			Antiangiogenic Therapy
		Treatment of Metastatic Bone Disease
		Special Considerations
			Treatment of Metastatic Breast Cancer in the Elderly
			Management of Metastatic Triple-Negative Breast Cancer
			Management of Metastatic Breast Cancer With Germline BRCA Mutations
		Monitoring Response to Therapy
		Future of Systemic Therapy for Metastatic Breast Cancer
		Selected References
		References
	70 Endocrine Therapy for Breast Cancer
		History of Endocrine Therapy in Breast Cancer
			Linking the Course of Advanced Breast Cancer to Female Reproductive Organs
			Recognizing Hormone Dependency for Certain Human Tumors
			Understanding Estrogen Action and Developing Antiestrogens
			The Modern Era of Endocrine Therapy
		General Strategies for Targeting the Hormonal Axis
			Hormone Assays
			Predictive Power of ER/PR Status
		Key Therapeutic Agents
			Selective Estrogen Receptor Modulators
				Tamoxifen
					Efficacy.
					Side Effects.
					Metabolism.
				Raloxifene
					Efficacy.
					Side Effects.
				Toremifene
					Efficacy.
					Side Effects.
				Other Selective Estrogen Receptor Modulators
			Aromatase Inhibitors
				Steroidal Versus Nonsteroidal Aromatase Inhibitors
				Early Aromatase Inhibitor Trials
				Aromatase Inhibitors Side Effects
			Selective Estrogen Receptor Downregulators
				Fulvestrant Side Effects
			Summary
		Ductal Carcinoma in Situ
		HR-Positive Invasive Breast Cancer: Adjuvant Treatment
			Predictive Tools for Use of Adjuvant Chemotherapy in HR-Positive Breast Cancer
				21-Gene Recurrence Score (Oncotype DX Assay)
				PAM-50
				70-Gene Assay (MammaPrint)
				ki67
				Breast Cancer Index (BCI)
				Summary
			Adjuvant Endocrine Therapy for ER- and/or PR-Positive Breast Cancer
				Premenopausal Women
					Ovarian Function Suppression.
				Postmenopausal Women
				Extended Duration of Endocrine Therapy
			Neoadjuvant Endocrine Therapy for HR-Positive Breast Cancer
		Advanced and Metastatic Breast Cancer: Treatment
			First-Line Therapy
			Prior Treatment With Nonsteroidal Aromatase Inhibitor
		Selected References
		References
	71 Immunologic Approaches to Breast Cancer Therapy
		Immunity and Breast Cancer
		Diagnostic Role of Tumor-Associated Autoantibodies
		Prognostic Role of Tumor-Infiltrating Lymphocytes
		Immunologic Effects of Standard Breast Cancer Therapies
		Breast Cancer Vaccines
		Adoptive T-Cell Therapy
		Immune Checkpoint Inhibitor Therapy
		Immuno-Prevention of Breast Cancer
		Conclusion
		Acknowledgments
		Conflict of Interest
		Selected References
		References
	72 Diagnosis and Management of Pleural Metastases and Malignant Effusion in Breast Cancer
		Pathogenesis
		Clinical Presentation
		Diagnosis
			Radiographic Findings
			Tissue Confirmation
				Thoracentesis and Studies on the Pleural Fluid
				Immunohistochemistry
			Tissue Biopsies
		Treatment: Indications, Approaches, and Complications
			Pleural Space Drainage
				Thoracentesis
				Indwelling Pleural Catheter
				Tube Thoracostomy
				Pleurodesis
			Surgical Intervention: Video-Assisted Thoracoscopic Surgery, Pleural Decortication, Pericardial Drainage
			Surgical Pleurectomy
			Patients With Trapped Lung
			Sclerosing Agents
		Prognosis
		Summary
		Selected References
		References
	73 Management of Central Nervous System Metastases in Breast Cancer
		Incidence
		Risk Factors
		Methods of Spread and Distribution
		Clinical Presentation
			Brain Metastasis
			Leptomeningeal Metastasis
			Epidural Spinal Cord Compression
		Diagnostic Evaluation
			Brain Metastases
			Leptomeningeal Metastases
			Spinal Cord Compression
		Treatment
			Prognosis
			Corticosteroids
			Anticonvulsants
			Whole-Brain Radiation Therapy
				Treatment Technique and Dose Fractionation
				Toxicity of Whole-Brain Radiation Therapy
			Surgery
				Surgical Intervention for Single Metastasis
				Surgery for Multiple Metastases
			Stereotactic Radiosurgery
				Stereotactic Radiosurgery Versus Surgery
				Whole-Brain Radiation Therapy Versus Whole-Brain Radiation Therapy Plus Stereotactic Radiosurgery Boost
				Stereotactic Radiosurgery Versus Whole-Brain Radiation Therapy
			Chemotherapy
			Radiation Sensitizers
			Recurrent Brain Metastasis
			Brain Metastases: Conclusions
			Treatment of Leptomeningeal Metastases
				Medical Management
				Chemotherapy
					Intrathecal Chemotherapy.
					Systemic Chemotherapy.
				Radiation
				Toxicity of Therapy
				Conclusions
			Treatment of Epidural Spinal Cord Compression
				Prognosis
				Corticosteroids
				Radiation
					Treatment Technique and Dose Schedule.
					Efficacy of Radiation Therapy.
				Radiation and Surgery
				Toxicity
				Recurrence
				Conclusions
		Selected References
		References
	74 Management of Pericardial Metastases in Breast Cancer
		Pericardial Effusion in Breast Cancer
			Pathology
			Pathophysiology
			Clinical Presentation
			Diagnostic Evaluation
			Treatment
			Postpericardiocentesis Diagnostics and Therapeutics
			Recurrent Pericardial Effusion
		Pericardial Constriction in Breast Cancer
			Pathology
			Pathophysiology
			Clinical Presentation
			Diagnostic Studies
			Treatment
		Selected References
		References
Section XVI: Special Presentations of Breast Cancer
	75 Bilateral Breast Cancer
		Risk Factors for Bilateral Breast Cancer
			Age
			Hereditary Breast Cancer
			Family History
			Radiation Exposure
			Invasive Lobular Carcinoma
			Lobular Carcinoma in Situ
		Impact of Advanced Imaging and Adjuvant Therapy on Bilaterality
			Magnetic Resonance Imaging and Contralateral Breast Cancer Detection
			Chemotherapy
			Tamoxifen
			Declining Incidence of CBC
		Prognosis of Bilateral Breast Cancer
		Contralateral Prophylactic Mastectomy
		Recommendations and Future Directions
		Selected References
		References
	76 Male Breast Cancer
		Epidemiology
		Risk Factors
		Clinical Features
		Diagnosis
		Pathology
		Treatment of Localized and Locally Advanced Disease
			Surgical Management
			Management of Regional Nodes
			Locally Advanced Disease
			Adjuvant Radiation Therapy
			Adjuvant Systemic Therapy
		Treatment of Metastatic Disease
		Prognosis
		Survivorship Issues and Surveillance
		Management Summary
		Selected References
		References
	77 Local Recurrence, the Augmented Breast, and the Contralateral Breast
		Locoregional Recurrence After Mastectomy
		Recurrence in the Reconstructed Breast
		Recurrence After Breast Conserving Therapy
		Breast Cancer in the Augmented Breast
		Breast Cancer After Skin-Sparing Mastectomy
		Cancer Risk in the Contralateral Breast
		Selected References
		References
	78 Carcinoma of the Breast in Pregnancy and Lactation
		Prognosis and Historical Perspective
		Diagnostic Evaluation and Staging During Pregnancy
			Imaging Studies During Pregnancy
			Breast Biopsy During Pregnancy
			Pathologic Findings
		Treatment
			Surgery
			Systemic Chemotherapy
			Radiation Therapy
		Special Issues
			Therapeutic Abortion
			BRCA Mutations and Pregnancy-Associated Breast Cancer
		Conclusion
		Selected References
		References
	79 Unknown Primary Presenting With Axillary Lymphadenopathy
		Incidence
		Diagnosis
			Selected Imaging
			Pathologic Evaluation
		Management
		Selected References
		References
	80 Clinical Management of the Patient at Increased or High Risk
		Breast Cancer Risk Assessment
			Qualitative Breast Cancer Risk Assessment
			Quantitative Breast Cancer Risk Assessment
		Risk Assessment Models Based on Nongenetic Factors
		Risk Assessment Models Based on Family History and Genetic Factors
			Breast Cancer Risk Assessment in the Clinical Setting
		Nongenetic Breast Cancer Risk Counseling
		Genetic Breast Cancer Risk Counseling
			Risk Management in the Clinical Setting
			Risk Reduction Options Based on Level of Risk
		High-Risk Women Secondary to Premalignant Lesions and Elevated Gail Risk
		High-Risk Women Secondary to Genetic Predisposition
			Risk-Based Screening Recommendations
		High-Risk Women Secondary to Elevated Gail Risk, Prior Thoracic Radiation at an Early Age, or Premalignant Lesions
		High-Risk Women Secondary to Known or Suspected Genetic Predisposition
		Conclusions
		Selected References
		References
Section XVII: Survivorship, Follow-Up Care, and Rehabilitation of the Breast Cancer Patient
	81 General Considerations for Follow-Up
		Surveillance for Locoregional Recurrences or New Primary Disease
		Detecting Distant Relapse
		Managing Long-Term and Late Effects of Cancer Treatment
			Lymphedema and Other Local Sequelae
			Osteoporosis
			Musculoskeletal Complaints
			Chemotherapy-Related Amenorrhea, Ovarian Dysfunction, and Infertility
			Pregnancy
			Hormonal Symptoms and Sexual Dysfunction
			Fatigue
			Cognitive Impairment
			Psychosocial Concerns
			Thrombosis
			Cardiac Disease
			Treatment-Related Cancers
		Non–Cancer-Related Care
		Survivorship Care Planning
		Conclusions and Future Directions
		Selected References
		References
	82 Management of Menopause in the Breast Cancer Patient
		What Is the Experience of Menopause in Women With Breast Cancer?
		Is Hormone Therapy an Option for Women With Breast Cancer?
		Alternatives to Estrogen-Based Therapy for Management of Vasomotor Symptoms
			Antidepressants
			Gabapentinoids
			Clonidine
			Progesterone Analogs
			Complementary and Alternative Methods
		Are Topical Estrogens an Option for Women With Breast Cancer?
		Alternatives to Topical Estrogens for Vulvovaginal Atrophy
		Depression
		Osteoporosis
		Cardiovascular Disease
		Conclusions
		Selected References
		References
	83 Rehabilitation
		Deconditioning
			Musculoskeletal System
			Cardiovascular System
			Cardiopulmonary Fitness
		Fatigue
			Screening and Diagnosis
			Treatment
		Upper Quadrant Dysfunction
			Pretreatment Upper Quadrant Function
			Biomechanics: Range of Motion, Scapular Control, Muscle Strength
			Correlation of Surgical Intervention and Upper Quadrant Dysfunction
			Impact of Impairments on Daily Activities
			Relationship to Physical Activity Level
			Screening
			Treatment
		Neuropathy
			Mononeuropathies
			Radiculopathy
			Brachial Plexopathy
			Chemotherapy-Induced Peripheral Neuropathy
				Taxanes
				Platinum Derivatives
				Vinca Alkaloids
			Diagnosis
			Treatment
				Acupuncture
		Pain
			Screening
			Treatment
		Exercise
		Cognitive Dysfunction
			Screening
			Treatment
		Vocational Rehabilitation
		Conclusion
		Acknowledgment
		Selected References
		References
	84 Psychosocial Consequences and Lifestyle Interventions
		Psychosocial Aspects of Breast Cancer
		Distress in Breast Cancer
			Screening for Distress
			Sources of Psychological Distress in Breast Cancer
				Hereditary Breast Cancer
				Diagnostic Process
				Surgery
				Adjuvant Therapy
				Cancer Survivorship
				Cancer Recurrence or Progression
			Special Consideration
				Males With Breast Cancer
				Very Young Breast Cancer Patients
			Psychosocial Intervention
				Timing of Intervention
				Types of Intervention
					Pharmacologic Interventions.
					Psychosocial Interventions
						Cognitive Behavioral Therapy.
						Supportive Psychotherapy.
						Psychoeducation.
						Social Work Services.
						Spiritual Services.
						Family and Couples Therapy.
		Lifestyle and Breast Cancer
			Epidemiologic Evidence Linking Breast Cancer and Lifestyle Factors
				Physical Activity
				Diet
				Body Weight
			Mechanisms
				Lifestyle Interventions With Quality of Life Outcomes
				Lifestyle Interventions With Disease End Points
		Conclusion
		Acknowledgments
		Selected References
		References
	85 Breast Cancer Survivorship
		Background
		Identification and Management of Late and Long-Term Effects of Breast Cancer and Treatment
		Fatigue
		Cognition
		Cardiac Dysfunction
			Breast Cancer Treatment–Specific Cardiovascular Disease Risk Factors
		Sexual Health, Body Image, and Relationship Issues
		Psychosocial Issues and Healthy Lifestyle
		Fertility and Menopause
		Understanding Cancer Risk and Management Strategies
		Imaging and Breast Cancer Survivors
		Development of Breast Cancer Survivorship Care: Program Development and Outcomes
		Conclusions
		Selected References
		References
Section XVIII: Medical and Legal Issues Specific to the Care of Breast Cancer
	86 Delayed Diagnosis of Symptomatic Breast Cancer
		Magnitude of the Problem
		Definition of Delayed Diagnosis of Breast Cancer
		Patient-Associated Delays in Diagnosis
			Studies of Patient-Associated Delays in Diagnosis
		Physician-Associated Delays in Diagnosis
			Physician Factors in Delayed Diagnosis of Breast Cancer
				Interval of Diagnostic Delay
				Specialty Training of Physicians
				Diagnostic Workups Requested by Physicians
			Clinical Scenarios Leading to the Delayed Diagnosis of Breast Cancer by Physicians
				Triad of Error for Delay in Diagnosis of Breast Cancer
					Young Age.
					Self-Discovered Breast Mass.
					False-Negative Mammogram.
			Delays Related to Pregnancy-Associated (Gestational) Breast Cancer
			Delays in Diagnosis Related to Male Breast Cancer
			Delays in Diagnosis Related to False-Negative Fine-Needle Aspiration Biopsy
			Miscellaneous Factors Leading to the Delayed Diagnosis of Breast Cancer
		Influence of Delayed Diagnosis of Breast Cancer on Survival
			Studies Showing an Adverse Effect of Diagnostic Delay on Survival
			Studies Showing No Effect of Diagnostic Delay on Survival
		Conclusion: How to Prevent the Delayed Diagnosis of Breast Cancer—Synopsis of Clinical Risk Prevention
		Selected References
		References
Index
	A
	B
	C
	D
	E
	F
	G
	H
	I
	J
	K
	L
	M
	N
	O
	P
	Q
	R
	S
	T
	U
	V
	W
	X
	Y
	Z