Management of the Breast and Axilla in the Neoadjuvant Setting

Preface
Contents
Contributors
Part I: History of Neoadjuvant Systemic Therapy in Breast Cancer
	Chapter 1: Neoadjuvant Therapy for Breast Cancer
		Evolution of the Indications for Neoadjuvant Therapy
		Current Evolution and Application of Preoperative Treatment Strategies
			Candidates for Neoadjuvant Therapy
			Patients with Temporary Contraindications for Surgery
			Regimens for Neoadjuvant Therapy (Table 1.1)
				Chemotherapy
				Targeted (Biologic) Therapy
		Achieving a Pathological Complete Response
			Treatment of Residual Disease in Either Breast or Lymph Nodes
		Summary
		References
	Chapter 2: The Macroscopic and Microscopic Evaluation of Breast and Axillary Lymph Node Specimens Following Neoadjuvant Systemic Therapy for Breast Cancer
		Macroscopic Examination of Breast Specimens Following NAST
		Microscopic Evaluation of Breast Specimens Following NAST
		Histologic Features of Primary Tumors Associated with Increased Rates of Pathologic Complete Response
		The Significance of Lymphovascular Invasion Following NAST
		The Significance of Residual Ductal Carcinoma In Situ Following NAST
		Tumor-Infiltrating Lymphocytes and Their Significance in Tumors Treated with NAST
		The Significance of Lymph Node Status Following NAST
		Macroscopic and Microscopic Evaluation of Lymph Node Specimens Following NAST
		Classification Systems Evaluating Specimens Following NAST
		Clarifications Regarding Reporting and Staging, Including AJCC 8th Edition Updates
		Reassessment of ER, PR, and HER2 Post-NAST
		Conclusion
		References
Part II: Pre- and Post-neoadjuvant Systemic Therapy Imaging Considerations
	Chapter 3: Radiology Case Presentations in Neoadjuvant Setting
	Chapter 4: Imaging of the Axilla and Approaches to Node-Negative Versus Node-Positive Disease at Presentation
		When to Image the Axilla
		Mammography
		Ultrasound
		Breast MRI
		Ultrasound-Guided Diagnostic Interventions
			Assessment of Concordance
		Response to Neoadjuvant Chemotherapy
		Localization
		Conclusion
		References
	Chapter 5: Guidelines for Imaging During Neoadjuvant Systemic Therapy
		Introduction
		Mammography
		Ultrasonography
		Functional Imaging
			Dynamic Contrast-Enhanced Magnetic Resonance Imaging (DCE-MRI/MRI)
			Contrast-Enhanced Digital Mammography (CEM/CEDM)
			Molecular Imaging
		Conclusion
		References
Part III: Neoadjuvant Systemic Therapy
	Chapter 6: Neoadjuvant Systemic Therapy for Breast Cancer Based on Underlying Tumor Biology
		Introduction
		Neoadjuvant Treatment Options
		Neoadjuvant Therapy in Hormone Receptor-Positive/HER2-Negative Breast Cancer (HR+/HER2-BC)
		Neoadjuvant Therapy in HER2-Positive Breast Cancer (HER2+BC)
			HER2-Targeted Therapies
			Neoadjuvant Chemotherapy for HER2+BC
			Neoadjuvant Therapy Options in Lower-Risk HER2+BC Patients and Those with Comorbidities
		Neoadjuvant Therapy for Triple-Negative Breast Cancer (TNBC)
		Immunotherapy for TNBC in the Neoadjuvant Setting
		Post-neoadjuvant Systemic Therapy
		Conclusion
		References
	Chapter 7: Adjuvant Versus Neoadjuvant Systemic Therapy
		Locally Advanced Breast Cancer: Embracing Neoadjuvant Systemic Therapy
			Primary Local-Regional Therapy: Surgery and Radiation
			Breast Cancer as a Systemic Disease
			Primary Systemic Therapy: Neoadjuvant Treatment
		Operable Breast Cancer: Benefits of Neoadjuvant Therapy
			Neoadjuvant Therapy Facilitates Breast Conservation
			Neoadjuvant Therapy Downstages Axillary Lymph Node Disease
		Goal of Neoadjuvant Therapy: Complete Pathologic Response (pCR)
			Improved Clinical Outcomes Associated with pCR
			Optimizing Neoadjuvant Therapy: Use of Targets
				Targeting HER2-Positive Disease
				Targeting Triple-Negative Disease
				Targeting Hormone Receptor-Positive Disease
		Residual Disease Post-neoadjuvant Therapy Informs Adjuvant Treatment
			High-Risk Disease: Triple Negative and HER2 Positive
			Hormone Receptor Positive
		Who Should Receive Adjuvant Therapy Alone?
		Conclusion
		References
	Chapter 8: Molecular Testing and Personalized Neoadjuvant Treatment
		Introduction
		Genomic Risk Scores and Neoadjuvant Therapy for Hormone Receptor-Positive/HER2-Negative Breast Cancer
			Genomic Risk Score and Response to Neoadjuvant Chemotherapy
			Genomic Risk Score and Response to Neoadjuvant Endocrine Therapy
		Dynamic Testing of Ki67 to Guide Neoadjuvant Therapy for Hormone Receptor-Positive/HER2-Negative Breast Cancer
		DNA Damage Repair Status to Guide Neoadjuvant Therapy
			Neoadjuvant PARP Inhibitor Therapy
			Neoadjuvant Platinum Chemotherapy and Biomarkers of DNA Repair Deficiency
		Evolving Neoadjuvant Treatment Strategies
			Neoadjuvant CDK4/6 Inhibition in HR+/HER2− Breast Cancer
			Neoadjuvant Immune Checkpoint Inhibition in Triple-Negative Breast Cancer
		Conclusion
		References
Part IV: Surgical Considerations in a Patient Receiving Neoadjuvant Systemic Therapy
	Chapter 9: Breast Cancer Imaging Pre- and Post-Neoadjuvant Systemic Therapy
		Background
		Monitoring Response
		Clinical Assessment
		Imaging
		Mammography
		Ultrasound
		Magnetic Resonance Imaging
		Functional Imaging Methods and Future Directions
		Contrast-Enhanced Spectral Mammography
		Molecular Breast Imaging
		Optical Imaging
		Additional Considerations
		References
	Chapter 10: Surgical Management of the Axilla in Node-Negative and Node-Positive Disease at Diagnosis
		Introduction
		Benefit of NAC
		Benefit of NET
		Feasibility of SLNB After NAC
			Clinically Node-Negative Patients
			Clinically Node-Positive Patients
		Evaluation of Clipped Node
		Role of Radiation Therapy
		Future Directions
		Conclusion
		References
	Chapter 11: Surgical Considerations and Expectations in Patients Receiving Neoadjuvant Chemotherapy and Neoadjuvant Endocrine Therapy
		Surgical Considerations After Neoadjuvant Chemotherapy
		Neoadjuvant Strategies for Triple-Negative and HER2-Positive Breast Cancer
		Neoadjuvant Strategies for HR-Positive HER2-Negative Breast Cancer
		Axillary Management After NET
		Conclusion
		References
Part V: The Role of Radiation Therapy in Patients Receiving Neoadjuvant Systemic Therapy
	Chapter 12: Regional Nodal Irradiation Considerations in Patients Receiving Neoadjuvant Systemic Therapy
		Introduction
			Rationale for Neoadjuvant Systemic Therapy
			Impact of Neoadjuvant Systemic Therapy on Adjuvant Radiation Recommendations
				What Is Regional Nodal Irradiation?
				What Is the Role of RNI After NST?
			Regional Nodal Irradiation Efficacy Established in the Adjuvant Setting
				Early Randomized Trials of RNI/PMRT, and Initial Treatment Guidelines
				Meta-Analyses
				Updated Meta-Analysis, Modern Randomized Trials, and New Guidelines
				Summary
		THE Role of RNI After NST
			Historical Perspective on RNI After Mastectomy in Patients that Receive NST
			LRR After NST in Clinical Trials Evaluating Chemotherapy Regimens: The Impact of Response
			LRR from PMRT/RNI Post-NST in Single Institution and Registry Retrospective Analyses
				Single Institutions
				Registry Analyses
			The Impact of Breast Cancer Subtype
			Summary: When Is RNI Recommended and When Is It Safe to Omit RNI After NST
		Special Situations: Sentinel Lymph Node Biopsy After NST and Neoadjuvant Anti-Endocrine Therapy
			Neoadjuvant Anti-Endocrine Therapy
			Surgical Management of the Axilla After NST
			Axillary Management After NET
		Prospective, Randomized Evaluation of Regional Nodal Irradiation in Patients with Clinically Node-Positive Disease Treated with Preoperative Systemic Therapy
		Clinical Evaluation of the Regional Lymphatics Prior to Initiation of Preoperative Systemic Therapy
		Radiotherapy Technique
		Conclusion
		References
Part VI: Pathology, Guidelines and Ongoing Clinical Trials
	Chapter 13: Pathology of Neoadjuvant Systemic Therapy Response
		Introduction
		Review of Pathology of Invasive Breast Carcinoma
		Important Clinical Data
		Gross Examination of Post-therapy Surgical Specimens
		Histopathologic Features in the Breast Following Neoadjuvant Therapy
		Pathologic Evaluation of Response to Neoadjuvant Chemotherapy
		Lymph Node Assessment After Neoadjuvant Therapy
		Neoadjuvant Hormonal Therapy
		Conclusion
		References
	Chapter 14: Guidelines for Neoadjuvant Systemic Therapy
		Introduction
		Goals of Neoadjuvant Systemic Therapy
			Multidisciplinary Management
		Patient Selection for Neoadjuvant Systemic Therapy
			Locally Advanced Inoperable Breast Cancer
				Definition
				Pretreatment Evaluation for Non-inflammatory Locally Advanced Breast Cancer
				Pretreatment Evaluation for Inflammatory Breast Cancer
				Clinical Stage Assignment
				Clinical Scenario 1: Inflammatory Breast Cancer
					Clinical Prognostic Stage IIIC, cT4d, cN2b, cM0, ER, PR, and HER2 Negative
				Clinical Scenario 2: Locally Advanced, Inoperable Breast Cancer, ER Positive, Premenopausal
					Clinical Prognostic Stage IIIB, cT4b, cN2, cM0, Grade 2 Invasive Ductal Carcinoma
				Clinical Scenario 3: Locally Advanced, Inoperable Breast Cancer, HER2 Positive
					Clinical Prognostic Stage IIIC, cT1mi, cN3, cM0, ER Negative, PR Negative, and HER2 Positive
				Clinical Scenario 4: Locally Advanced, Inoperable Breast Cancer, Triple-Negative Breast Cancer
		Neoadjuvant Systemic Therapy for Operable Breast Cancer
			Downstaging Disease (Stage IIB–IIIA)—Tailoring Surgical Options
				Prognostic Information
				Impact on Adjuvant Systemic Recommendations—Tailoring Medical Therapy
				Delay in Surgery Is Needed
				Pretreatment Evaluation
				Multidisciplinary Management
			Hormone-Receptor-Positive Breast Carcinoma
				Clinical Scenario 1: Hormone-Receptor-Positive, Postmenopausal Patient. Clinical Stage IIIA cT2, cN2b, cM0
					Goal: Downstaging—Tailoring Surgical Options
				Clinical Scenario 2: Hormone-Receptor-Positive, Premenopausal Patient. Clinical Stage IIB, cT2, cN1, cM0
					Goal: Downstaging—Tailoring Surgical Options
				Clinical Scenario 3: Low Grade ER Positive, Postmenopausal Patient. Clinical Stage IIB, cT2, cN1, cM0
					Goal: Downstaging—Tailoring Surgical Options
				Clinical Scenario 4: Hormone-Receptor-Positive (Premenopausal Patient) with Clinical Stage IIA, Multifocal cT2, cN1a, cM0 Grade 2 Invasive Ductal Carcinoma, ER Positive, PR Positive, and HER2 Negative
					Goal: Reducing Delay in Initiating Systemic Therapy While Surgery and Reconstruction Are Being Planned
			HER2-Positive Breast Cancer
				Locally Advanced, Node Positive or High-Risk Node Negative
				Clinical Scenario 1: HER2-Positive Breast Carcinoma. Clinical Stage IIIA, cT2, cN2a, cM0, ER Negative, PR Negative, HER2 Positive
					Goal: Downstage Disease to Improve Surgical Options and to Tailor Adjuvant Therapy Recommendations Based on Pathologic Response to Therapy
				Clinical Scenario 2: Clinical Stage IIB HER2-Positive Breast, ER Positive Breast Cancer
					Goal: Downstage Disease to Improve Surgical Options and to Tailor Adjuvant Therapy Based on Pathologic Response to Therapy
				Clinical Scenario 3: Clinical Stage IIA HER2 ER Negative, HER2 Positive Breast Cancer
					Goal: Downstage Disease to Improve Surgical Options and to Tailor Adjuvant Therapy Based on Pathologic Response to Therapy
				Clinical Scenario 4: Clinical Stage IA, cT1c, cN0 Breast Carcinoma, ER Negative, HER2 Positive
					Upfront Surgery Is Preferred for Accurate Staging with Adjuvant Systemic Therapy Based on Pathologic Staging
				Clinical Scenario 5. Clinical Stage IA, cT1c, cN0, HER2-Positive, ER Positive Breast Carcinoma
					Planned Surgery Is Expected to Be Delayed
			Triple-Negative Breast Cancer
				Locally Advanced, Node Positive or High-Risk Node Negative
				Scenario 1. Premenopausal Patient with Clinical Stage IIIC Triple-Negative Breast Cancer. BRCA2 Carrier
					Goals: Downstage Disease to Improve Surgical Options and to Tailor Adjuvant Therapy Based on Pathologic Response to Therapy
				Clinical Scenario 2. Anatomic Stage IIB (cT2, cN1) Triple-Negative Breast Carcinoma
					Goals: Downstage Disease to Improve Surgical Options and to Tailor Adjuvant Therapy Based on Pathologic Response to Therapy
				Clinical Scenario 3. Clinical Stage IIB, cT2, cN1 Triple-Negative Breast Carcinoma
					Goal: Downstage Disease to Improve Surgical Options and to Tailor Adjuvant Therapy Based on Pathologic Response to Therapy
				Clinical Scenario 4: Clinical Stage IIB, cT2, cN0, Triple-Negative Breast Carcinoma
					Goals: To Downstage Local-Regional Disease and Assess Pathologic Response to Therapy
				Clinical Scenario 5: Clinical Stage IB, cT1c, cN0, cM0 Triple-Negative Breast Carcinoma
					Goals: To Assess Response to Therapy and Inform Options for Adjuvant Therapy
				Clinical Scenario 6: Clinical Stage IA, cT1a, cN0 Triple-Negative Breast Carcinoma
					Upfront Surgical Management Is Indicated for Accurate Staging with Adjuvant Systemic Therapy If Indicated Based on Pathologic Staging
		Summary
		References
	Chapter 15: Ongoing Clinical Studies and Future Directions
		Introduction
		Hormone-Receptor-Positive Breast Cancer
		HER2-Positive Breast Cancer
		Triple Negative Breast Cancer
		Surgical Management and De-Escalation
		Novel Strategies
		Future Directions
		References
Index