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
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