Breast Cancer Research and Treatment: Innovative Concepts

Foreword
Contents
1 Antibody–Drug Conjugates: A New Therapeutic Approach for Triple-Negative Breast Cancer
	1 Introduction
	2 Mechanisms of Action of Antibody–Drug Conjugates
	3 Antibody–Drug Conjugates in Triple-Negative Breast Cancer
		3.1 Antibody–Drug Conjugates Targeting Trophoblast Cell-Surface Antigen 2 (Trop-2)
		3.2 Antibody–drug Conjugates Targeting LIV1
		3.3 Antibody–Drug Conjugates HER2 (Human Epidermal Growth Factor Receptor-2)
		3.4 Antibody–Drug Conjugates Targeting HER3 (Human Epidermal Growth Factor Receptor-3)
		3.5 Antibody–Drug Conjugates Targeting Glycoprotein Non-metastatic B (GPNMB)
		3.6 Other ADCs for TNBC
	4 Conclusion
	References
2 Immune-Checkpoint Inhibitors: A New Line of Attack in Triple-Negative Breast Cancer
	1 Introduction
	2 Overview of Mechanisms Involved in the Immune-Checkpoint Blockade in Cancer
		2.1 CTLA-4 Pathway
		2.2 PD-1/PD-L1 Axis
		2.3 Other Immune Checkpoints
	3 Clinical Trials of Immune-Checkpoint Inhibitors in TNBC
		3.1 Immune-Checkpoint Inhibitors as Single Agents
		3.2 Immune-Checkpoint Inhibitors in Combinatorial Approaches
	4 Biomarkers for Immune-Checkpoint Blockade
	5 Conclusion
	References
3 Screening Programs for Breast Cancer: Toward Individualized, Risk-Adapted Strategies of Early Detection
	1 Breast Cancer: A Disease of Global Public Health Interest
		1.1 Mammography Based Screening of Breast Cancer
	2 Risk-Adapted Individualization of Breast Cancer Screening
		2.1 Risk-Based Escalation of Screening Interventions
		2.2 Risk-Based De-Escalation of Screening Interventions
		2.3 Customization of Breast Cancer Screening Based on Comprehensive Risk Assessment
	3 The Current Practice of Screening Individualization: The High-Risk Setting
	4 The Tyrer-Cuzick Model
	5 The BRCAPro Model
	6 The Gail Model
	7 The Breast Cancer Surveillance Consortium Risk Calculator
	8 Perspectives of Screening Individualization at Population Level
	9 Innovative Diagnostic Technologies with Potential in Breast Cancer Screening
	10 Artificial Intelligence for Risk-Definition
	11 Liquid Biopsy for Cancer Screening
	12 Conclusion
	References
4 Transversal Perspectives of Integrative Oncology Care in Gastric and Lobular Breast Cancer
	1 Introduction
	2 Genetic Alterations in Lobular Breast Cancer and Hereditary Diffuse Gastric Cancer: The Role of CDH1 and Other Genes
	3 Screening Strategies and Prophylactic Procedures for Lobular Breast Cancer and Gastric Cancer
		3.1 Gastric Cancer Screening
		3.2 Lobular Breast Cancer Screening
		3.3 Other Kinds of Tumors in CDH1 Mutated Patients: Colorectal Cancer Screening
	4 Risk Assessment and Prophylactic Procedures in Germline CDH1 Carriers
	5 CDH1 Carrier Clinical Management as the Paradigm for Integrated Oncology Care
	6 Conclusions
	References
5 Assessment and Response to Neoadjuvant Treatments in Breast Cancer: Current Practice, Response Monitoring, Future Approaches and Perspectives
	1 Introduction
	2 Breast Cancer Today
		2.1 Epidemiology and Risk Factors
		2.2 Tumor Classification
		2.3 TNM Staging
	3 Current Practice
		3.1 Neoadjuvant Chemotherapy (NAC)
		3.2 Treatment Response
	4 Response Monitoring
		4.1 Clinical Examination
		4.2 Ultrasound (US)
		4.3 Mammography
		4.4 Magnetic Resonance Imaging (MRI)
		4.5 Positron Emission Tomography (PET)
	5 Future Perspectives and Approaches
		5.1 MRI Fast Protocols
		5.2 MRI Spectroscopy (MRS)
		5.3 Dedicated Breast PET
		5.4 Breast-Specific Gamma Imaging (BSGI)
		5.5 Radiomics
	6 Conclusion
	References
6 Estimating the Benefit of Preoperative Systemic Therapy to Reduce the Extent of Breast Cancer Surgery: Current Standard and Future Directions
	1 Introduction
	2 Axillary Surgery
		2.1 Staging of the Axilla in cN0 Patients at Presentation
		2.2 Predictors of ypN0 After PST in cN0 Patients—Toward Omission of SLNB in cN0
		2.3 Staging of the Axilla in cN+ Patients at Presentation
		2.4 Tailoring Locoregional Therapy for Node-Positive Patients Who Achieve Nodal Pathological Complete Response After PST
		2.5 Tailoring Locoregional Therapy for Node-Positive Patients Who Fail to Achieve Nodal Pathological Complete Response with PST
	3 Breast Surgery
		3.1 Effectiveness of PST in Increasing Rates of Breast Conservation
		3.2 Local Control Following Breast Surgery Downstaging
		3.3 Margin Width After PST
		3.4 Elimination of Breast Surgery in Exceptional Responders
	4 Conclusion
	References
7 A Precise Approach for Radiotherapy of Breast Cancer
	1 Introduction to Radiotherapy
	2 Treatment of Early-Stage Disease
		2.1 Current Approach
		2.2 Future Directions
		2.3 Biomarker Directed Radiotherapy
		2.4 Dose-Escalation
	3 Treatment of Locally Advanced Disease
		3.1 Neoadjuvant Therapy
		3.2 Regional Nodal Management
		3.3 Post-mastectomy Radiotherapy
		3.4 Hypofractionated PMRT
		3.5 Future Directions
	4 Current Controversies
		4.1 Radiotherapy After Immediate Breast Reconstruction
	5 Metastatic Breast Cancer
		5.1 Oligometastatic Disease
		5.2 Polymetastatic Disease
	6 Conclusion
	References
8 Fast Mimicking Diets and Other Innovative Nutritional Interventions to Treat Patients with Breast Cancer
	1 Introduction
	2 Overview of Nutritional Interventions of Food Deprivation
		2.1 Caloric Restriction (CR)
		2.2 Fasting
	3 Fast Mimicking Diet
	4 Preclinical Rational of Fast Mimicking Diet in Breast Cancer Treatment
	5 Clinical Trials Assessing the Role of FMD in Breast Cancer Treatment
	6 The Next Step: Clinical Trials Investigating Fast Mimicking Molecules
	7 Other Innovative Nutritional Interventions for Breast Cancer Patients
	8 Conclusion
	References
9 Mechanisms of Endocrine Resistance in Hormone Receptor-Positive Breast Cancer
	1 Introduction
	2 Mechanisms of Resistance to Endocrine Therapy
		2.1 Estrogen Receptor Expression Loss
		2.2 ESR1 Mutations
		2.3 Receptor Tyrosine Kinases
		2.4 PI3K/AKT/mTOR Pathway Alterations
		2.5 MAPK Pathway Alterations
		2.6 Cell Cycle Regulators
	3 Conclusions and Future Perspectives
	References
10 Innovative Therapeutic Approaches for Patients with HER2-Positive Breast Cancer
	1 Introduction
	2 Currently Approved Anti-HER2 Agents
		2.1 Monoclonal Antibodies
	3 Trastuzumab
	4 Pertuzumab
	5 Margetuximab
		5.1 Tyrosine Kinase Inhibitors
	6 Lapatinib
	7 Neratinib
	8 Tucatinib
	9 Pyrotinib
		9.1 Antibody–drug Conjugates
	10 Ado-Trastuzumab Emtansine
	11 Fam-Trastuzumab Deruxtecan-Nxki (T-DXd)
	12 Trastuzumab Duocarmazine
	13 Disitamab Vedotin
		13.1 XMT-1522 (TAK-522)
		13.2 MM-302
		13.3 A166
		13.4 ARX788
		13.5 PF-06804103
	14 Innovative Experimental Treatments for HER2-Positive Breast Cancer
		14.1 Bispecific Antibodies
	15 Immune Cell Engagement
	16 Targeting Tumour-Associated Antigen (TAA)
	17 Ab-Drug Conjugation
		17.1 Vaccines
	18 NeuVax
		18.1 GP2
		18.2 AE37
	19 Other Vaccine Strategies
		19.1 CAR-T Against HER2
	20 Beyond HER2: Complementary Molecular Biomarkers and Other Emerging Therapies
		20.1 PI3K Pathway
		20.2 Hormone Receptor and CDK4/6 Inhibitors, and MAPK Pathway Disrupters
		20.3 PDL-1/TILs and Immune-Checkpoint Inhibitors
		20.4 HER2 Heterogeneity
	21 Conclusion
	References
11 Breast Cancer Brain Metastases: Achilles’ Heel in Breast Cancer Patients’ Care
	1 Introduction
	2 Incidence of Breast Cancer-Associated Brain Metastasis and Survival Outcomes
	3 Local Therapy Modalities to Control CNS Spreading
	4 The Blood Brain/Tumor Barrier and Brain Microenvironment
	5 Systemic Therapy
	6 The Paradigm of Brain Metastases in HER2-Positive Breast Cancer
	7 Conclusions
	References
12 New Concepts in Cardio-Oncology
	1 Introduction
	2 Cardiotoxicity of Chemotherapy
		2.1 Anthracyclines
		2.2 Taxanes
		2.3 Capecitabine and 5-FU
		2.4 Gemcitabine
		2.5 Cyclophosphamide
		2.6 Vinorelbine
		2.7 Platinum Salts
		2.8 Eribulin
	3 Cardiotoxicity of HER2-Targeted Agents
		3.1 Monoclonal Antibodies
		3.2 Tyrosine-Kinase Inhibitors (TKIs)
		3.3 Antibody–Drug Conjugates (ADCs)
	4 Cardiotoxicity of Endocrine and Combination Therapy
		4.1 Tamoxifen
		4.2 Aromatase Inhibitors
		4.3 Fulvestrant
		4.4 Cyclin-Dependent Kinase Inhibitors
		4.5 MTOR/PI3Kinhibitors
	5 Cardiotoxicity of PolyADP-Ribose Polymerase Inhibitors (PARPi) and Angiogenesis Inhibitors
	6 Cardiotoxicity of Immunotherapy
	7 Prevention and Management
		7.1 Screening
		7.2 Prevention
		7.3 Early Detection, Monitoring, and Treatment
	8 Conclusion
	References
13 Next-Generation Sequencing for Advanced Breast Cancer: What the Way to Go?
	1 Next-Generation Sequencing for Cancer Care
	2 Actionability of Genetic Alterations: How to Prioritize?
	3 The Molecular Tumour Board Paradigm: From Clinical Actionability to the Treatment Decision-Making
	4 Implementing ESCAT in the Clinical Practice for Breast Cancer
	5 Challenges of NGS in Breast Cancer
	6 Conclusion
	References
14 The Global Landscape on the Access to Cancer Medicines for Breast Cancer: The ONCOLLEGE Experience
	1 Essential Medicines: The Role of Trastuzumab in Breast Cancer Treatment
	2 Access to Trastuzumab—Patient Aspect
		2.1 Access to Testing
		2.2 Out-of-Pocket Payment and Financial Toxicity of Access to Trastuzumab
	3 Aspects of Access Management: The Pharmaceutical Aspects
		3.1 Investigational Phase—From Clinical Trials to Expanded Access
		3.2 Marketed Phase—From Pricing to Patient Assistance Programs
		3.3 Biosimilars
		3.4 Fixed-Dose, New Formulation and Optimized Schedules
	4 Conclusion and Future Directions
	References