Medscape InDiscussion: Breast Cancer and HER2

Drs Kathy D. Miller and Sara M. Tolaney discuss advancements and considerations for optimizing treatment for HER2-positive breast cancer, focusing on balancing efficacy with minimizing toxicity. Relevant disclosures can be found with the episode show notes on Medscape https://www.medscape.com/viewarticle/1001124. The topics and discussions are planned, produced, and reviewed independently of advertisers. This podcast is intended only for US healthcare professionals. Resources Adjuvant Paclitaxel and Trastuzumab for Node-Negative, HER2-Positive Breast Cancer https://pubmed.ncbi.nlm.nih.gov/25564897/ Adjuvant Paclitaxel and Trastuzumab for Node-Negative, HER2-Positive Breast Cancer: Final 10-Year Analysis of the Open-Label, Single-Arm, Phase 2 APT Trial https://pubmed.ncbi.nlm.nih.gov/36858723/ Trastuzumab Emtansine for Residual Invasive HER2-Positive Breast Cancer https://pubmed.ncbi.nlm.nih.gov/30516102/ Adjuvant Trastuzumab Emtansine Versus Paclitaxel in Combination With Trastuzumab for Stage I HER2-Positive Breast Cancer (ATEMPT): A Randomized Clinical Trial https://pubmed.ncbi.nlm.nih.gov/34077270/ Adjuvant Trastuzumab Emtansine Versus Paclitaxel Plus Trastuzumab for Stage I Human Epidermal Growth Factor Receptor 2-Positive Breast Cancer: 5-Year Results and Correlative Analyses From ATEMPT https://pubmed.ncbi.nlm.nih.gov/38935923/ Treatment Discontinuation, Patient-Reported Toxicities and Quality-of-Life by Age Following Trastuzumab Emtansine or Paclitaxel/Trastuzumab (ATEMPT) https://pubmed.ncbi.nlm.nih.gov/36450763/ ATEMPT 2.0: Adjuvant T-DM1 vs TH https://clinicaltrials.gov/study/NCT04893109 Neoadjuvant Treatment With HER2-Targeted Therapies in HER2-Positive Breast Cancer: A Systematic Review and Network Meta-Analysis https://pubmed.ncbi.nlm.nih.gov/35158791/ 5-Year Analysis of Neoadjuvant Pertuzumab and Trastuzumab in Patients With Locally Advanced, Inflammatory, or Early-Stage HER2-Positive Breast Cancer (NeoSphere): A Multicentre, Open-Label, Phase 2 Randomised Trial https://pubmed.ncbi.nlm.nih.gov/27179402/ CompassHER2-pCR: Decreasing Chemotherapy for Breast Cancer Patients After Pre-surgery Chemo and Targeted Therapy https://clinicaltrials.gov/study/NCT04266249 Alliance A011801 (CompassHER2 RD): Postneoadjuvant T-DM1 + Tucatinib/Placebo in Patients With Residual HER2-Positive Invasive Breast Cancer https://pubmed.ncbi.nlm.nih.gov/34636255/ Incidence of Interstitial Lung Disease and Cardiotoxicity With Trastuzumab Deruxtecan in Breast Cancer Patients: A Systematic Review and Single-Arm Meta-Analysis https://pubmed.ncbi.nlm.nih.gov/37481956/ STOP-HER2: Stopping Trastuzumab in HER2+ MBC https://clinicaltrials.gov/study/NCT05721248

Drs Kathy D. Miller and Sunil S. Badve discuss the importance of identifying HER2-low patients, those with ultra-low staining, and the benefit of targeted ADCs. Relevant disclosures can be found with the episode show notes on Medscape https://www.medscape.com/viewarticle/1001160. The topics and discussions are planned, produced, and reviewed independently of advertisers. This podcast is intended only for US healthcare professionals. Resources Breast Cancer and HER2 https://emedicine.medscape.com/article/1689966-overview Human Epidermal Growth Factor Receptor 2 Testing in Breast Cancer: ASCO-College of American Pathologists Guideline Update https://pubmed.ncbi.nlm.nih.gov/37284804/ T-DXd Improves Progression-Free Survival in Patients With Breast Cancer Previously Treated With Endocrine Therapy https://ascopost.com/news/june-2024/t-dxd-improves-progression-free-survival-in-patients-with-breast-cancer-previously-treated-with-endocrine-therapy/ Alliance A011801 (compassHER2 RD): Postneoadjuvant T-DM1 + Tucatinib/Placebo in Patients With Residual HER2-Positive Invasive Breast Cancer https://pubmed.ncbi.nlm.nih.gov/34636255/

Drs Kathy D. Miller and Heather A. Parsons explore the complexities and evolving strategies in managing HER2+ oligometastatic breast cancer, tackling curative intent, treatment duration, and the promise of emerging biomarkers. Relevant disclosures can be found with the episode show notes on Medscape https://www.medscape.com/viewarticle/1001335. The topics and discussions are planned, produced, and reviewed independently of advertisers. This podcast is intended only for US healthcare professionals. Resources Breast Cancer and HER2 https://emedicine.medscape.com/article/1689966-overview De Novo Oligometastatic Breast Cancer https://pubmed.ncbi.nlm.nih.gov/37607325/ A Review of Allogeneic Hematopoietic Stem Cell Transplantation in Metastatic Breast Cancer https://pubmed.ncbi.nlm.nih.gov/30233772/ Early Local Therapy for the Primary Site in De Novo Stage IV Breast Cancer: Results of a Randomized Clinical Trial (EA2108) https://pubmed.ncbi.nlm.nih.gov/34995128/ Stereotactic Body Radiation Therapy for Oligometastatic Breast Cancer: A Retrospective Multicenter Study https://pubmed.ncbi.nlm.nih.gov/34778049/ NRG-BR002: A Phase IIR/III Trial of Standard of Care Systemic Therapy With or Without Stereotactic Body Radiotherapy (SBRT) and/or Surgical Resection (SR) for Newly Oligometastatic Breast Cancer (NCT02364557) https://ascopubs.org/doi/10.1200/JCO.2022.40.16_suppl.1007 Systemic Therapies for HER2-Positive Advanced Breast Cancer https://pubmed.ncbi.nlm.nih.gov/38201451/ Oligometastatic Breast Cancer and Metastasis-Directed Treatment: An Aggressive Multimodal Approach to Reach the Cure https://pubmed.ncbi.nlm.nih.gov/36950272/ Circulating Tumor Biomarkers in Early-Stage Breast Cancer: Characteristics, Detection, and Clinical Developments https://pubmed.ncbi.nlm.nih.gov/37941557/ Minimal Residual Disease (MRD) Detection in Solid Tumors Using Circulating Tumor DNA: A Systematic Review https://pubmed.ncbi.nlm.nih.gov/37636270/

Drs Kathy Miller and Nancy U. Lin discuss central nervous system involvement in HER2-positive breast cancer, including the biology and management of patients. Relevant disclosures can be found with the episode show notes on Medscape https://www.medscape.com/viewarticle/1001336. The topics and discussions are planned, produced, and reviewed independently of advertisers. This podcast is intended only for US healthcare professionals. Resources Breast Cancer and HER2 https://emedicine.medscape.com/article/1689966-overview Brain Metastases in HER2-Positive Breast Cancer: Current and Novel Treatment Strategies https://pubmed.ncbi.nlm.nih.gov/34208287/ Adjuvant Trastuzumab Emtansine in HER2-Positive Breast Cancer Patients With HER2-Negative Residual Invasive Disease in KATHERINE https://pubmed.ncbi.nlm.nih.gov/36117201/ Raising the Bar for Real-World Data in Oncology: Approaches to Quality Across Multiple Dimensions https://pubmed.ncbi.nlm.nih.gov/38241599/ Anti-Angiogenic Therapy: Current Challenges and Future Perspectives https://pubmed.ncbi.nlm.nih.gov/33916438/ ALK-Positive Lung Cancer: A Moving Target https://pubmed.ncbi.nlm.nih.gov/36797503/ Radiotherapy for HER 2 Positive Brain Metastases: Urgent Need for a Paradigm Shift https://pubmed.ncbi.nlm.nih.gov/35326665/ Tailoring Neoadjuvant Therapy in Human Epidermal Growth Factor Receptor 2-Positive Early Breast Cancer: Recent Advances and Strategies https://pubmed.ncbi.nlm.nih.gov/38471052/ Stereotactic Radiosurgery and Local Control of Brain Metastases From Triple-Negative Breast Cancer https://pubmed.ncbi.nlm.nih.gov/36433878/ Multi-institutional Validation of Brain Metastasis Velocity, a Recently Defined Predictor of Outcomes Following Stereotactic Radiosurgery https://pubmed.ncbi.nlm.nih.gov/31526671/ Hippocampal Avoidance Whole Brain Radiotherapy in Brain Metastasis Using Volumetric Modulated Arc Therapy: Experience From a Regional Cancer Centre of Eastern India https://pubmed.ncbi.nlm.nih.gov/37795235/ Leptomeningeal Metastases https://emedicine.medscape.com/article/1156338-overview Randomized Phase II Trial of Proton Craniospinal Irradiation Versus Photon Involved-Field Radiotherapy for Patients With Solid Tumor Leptomeningeal Metastasis https://pubmed.ncbi.nlm.nih.gov/35802849/ A Phase I/II Study of Intrathecal Trastuzumab in Human Epidermal Growth Factor Receptor 2-Positive (HER2-Positive) Cancer With Leptomeningeal Metastases: Safety, Efficacy, and Cerebrospinal Fluid Pharmacokinetics https://pubmed.ncbi.nlm.nih.gov/35948282/ Tucatinib-Trastuzumab-Capecitabine for Treatment of Leptomeningeal Metastasis in HER2+ Breast Cancer: TBCRC049 Phase 2 Study Results https://ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.2018 Radiological Response of Leptomeningeal Metastases According to Revised RANO Criteria Is Associated With Overall Survival in Breast Cancer Patients https://pubmed.ncbi.nlm.nih.gov/37243480/

Kathy D. Miller, MD, and Stephanie L. Graff, MD, discuss sequencing of ADCs for metastatic HER2-low breast cancer including sequencing, toxicities, and clinical trials. Relevant disclosures can be found with the episode show notes on Medscape https://www.medscape.com/viewarticle/1001337. The topics and discussions are planned, produced, and reviewed independently of advertisers. This podcast is intended only for US healthcare professionals. Resources Breast Cancer and HER2 https://emedicine.medscape.com/article/1689966-overview Antibody-Drug Conjugates in Breast Cancer: Current Status and Future Directions https://pubmed.ncbi.nlm.nih.gov/37762027/ Pathological Identification of HER2-Low Breast Cancer: Tips, Tricks, and Troubleshooting for the Optimal Test https://pubmed.ncbi.nlm.nih.gov/37077201/ Trastuzumab Deruxtecan in Previously Treated HER2-Low Advanced Breast Cancer https://pubmed.ncbi.nlm.nih.gov/35665782/ Abemaciclib Combined With Endocrine Therapy for the Adjuvant Treatment of HR+, HER2-, Node-Positive, High-Risk, Early Breast Cancer (monarchE) https://pubmed.ncbi.nlm.nih.gov/32954927/ Sequencing Antibody Drug Conjugates in Breast Cancer: Exploring Future Roles https://pubmed.ncbi.nlm.nih.gov/38132377/ Subtypes of Breast Cancer https://www.ncbi.nlm.nih.gov/books/NBK583808/ Parallel Genomic Alterations of Antigen and Payload Targets Mediate Polyclonal Acquired Clinical Resistance to Sacituzumab Govitecan in Triple-Negative Breast Cancer https://pubmed.ncbi.nlm.nih.gov/34404686/ Trastuzumab Deruxtecan in Metastatic Breast Cancer With Variable HER2 Expression: The Phase 2 DAISY Trial https://pubmed.ncbi.nlm.nih.gov/37488289/ Decoding TROP2 in Breast Cancer: Significance, Clinical Implications, and Therapeutic Advancements https://pubmed.ncbi.nlm.nih.gov/37954074/ TReatment of ADC-Refractory Breast CancEr With Dato-DXd or T-DXd: TRADE DXd (TRADE DXd) https://clinicaltrials.gov/study/NCT06533826

Drs Kathy Miller and Francisco J. Esteva discuss testing and therapeutic options for the new classification of HER2–ultra-low breast cancer. Relevant disclosures can be found with the episode show notes on Medscape https://www.medscape.com/viewarticle/1001338. The topics and discussions are planned, produced, and reviewed independently of advertisers. This podcast is intended only for US healthcare professionals. Resources Breast Cancer and HER2 https://emedicine.medscape.com/article/1689966-overview Prevalence of "HER2 Ultra-Low" Among Patients With Advanced Breast Cancer With Historical IHC0 Status https://ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.e13156 Targeting HER2-Positive Breast Cancer: Advances and Future Directions https://pubmed.ncbi.nlm.nih.gov/36344672/ Are There More HER2 FISH in the Sea? An Institution's Experience in Identifying HER2 Positivity Using Fluorescent In Situ Hybridization in Patients With HER2 Negative Immunohistochemistry https://pubmed.ncbi.nlm.nih.gov/37936021/ Trastuzumab Deruxtecan (T-DXd) vs Physician's Choice of Chemotherapy (TPC) in Patients (Pts) With Hormone Receptor-Positive (HR+), Human Epidermal Growth Factor Receptor 2 (HER2)-Low or HER2-Ultralow Metastatic Breast Cancer (MBC) With Prior Endocrine Therapy (ET): Primary Results From DESTINY-Breast06 (DB-06) https://ascopubs.org/doi/10.1200/JCO.2024.42.17_suppl.LBA1000 The American Society of Clinical Oncology-College of American Pathologists Guideline Update for Human Epidermal Growth Factor Receptor 2 Testing in Breast Cancer https://pubmed.ncbi.nlm.nih.gov/37303241/ Prognostic Relevance of the HER2 Status of Circulating Tumor Cells in Metastatic Breast Cancer Patients Screened for Participation in the DETECT Study Program https://pubmed.ncbi.nlm.nih.gov/34839105/ Estrogen and Progesterone Receptor Testing in Breast Cancer: ASCO/CAP Guideline Update https://pubmed.ncbi.nlm.nih.gov/31928404/ Adjuvant Therapy for Breast Cancer https://emedicine.medscape.com/article/1946040-overview Tumor Infiltrating Lymphocytes (TILs) and PD-L1 Expression in Breast Cancer: A Review of Current Evidence and Prognostic Implications From Pathologist's Perspective https://pubmed.ncbi.nlm.nih.gov/37760449/

Drs Kathy Miller and Bonnie Ky discuss cardiovascular concerns with HER2-targeted therapies and how to work with cardiology colleagues for the best treatment outcomes. Relevant disclosures can be found with the episode show notes on Medscape https://www.medscape.com/viewarticle/1002981. The topics and discussions are planned, produced, and reviewed independently of advertisers. This podcast is intended only for US healthcare professionals. Resources Breast Cancer and HER2 https://emedicine.medscape.com/article/1689966-overview Risk of Trastuzumab-Related Cardiotoxicity in Early Breast Cancer Patients: A Prospective Observational Study https://pubmed.ncbi.nlm.nih.gov/25548585/ MUGA Scan https://www.ncbi.nlm.nih.gov/books/NBK564365/ Myocardial Strain Imaging: Theory, Current Practice, and the Future https://pubmed.ncbi.nlm.nih.gov/39269417/ Adjuvant Paclitaxel and Trastuzumab for Node-Negative, HER2-Positive Breast Cancer: Final 10-Year Analysis of the Open-Label, Single-Arm, Phase 2 APT Trial https://pubmed.ncbi.nlm.nih.gov/36858723/ Risk Stratification for Trastuzumab-Induced Cardiac Dysfunction and Potential Implications for Surveillance https://pubmed.ncbi.nlm.nih.gov/40246379/ Cardiac Safety of Reduced Cardiotoxicity Surveillance During HER2-Targeted Therapy https://pubmed.ncbi.nlm.nih.gov/40537192/ Permissive Cardiotoxicity: The Clinical Crucible of Cardio-Oncology https://pubmed.ncbi.nlm.nih.gov/36213359/ Neprilysin Inhibition in the Prevention of Anthracycline-Induced Cardiotoxicity https://pubmed.ncbi.nlm.nih.gov/36612307/ Prospective Evaluation of the Cardiac Safety of HER2-Targeted Therapies in Patients With HER2-Positive Breast Cancer and Compromised Heart Function: The SAFE-HEaRt Study https://pubmed.ncbi.nlm.nih.gov/30852761/ Safety of Continuing Trastuzumab Despite Mild Cardiotoxicity: A Phase I Trial https://pubmed.ncbi.nlm.nih.gov/34396157/

Drs Kathy Miller and Alexandra Thomas discuss important toxicities for breast cancer HER2-targeted therapies and how to improve the patient experience. Relevant disclosures can be found with the episode show notes on Medscape https://www.medscape.com/viewarticle/1002982. The topics and discussions are planned, produced, and reviewed independently of advertisers. This podcast is intended only for US healthcare professionals. Resources Breast Cancer and HER2 https://emedicine.medscape.com/article/1689966-overview Polyhydramnios and Oligohydramnios https://emedicine.medscape.com/article/975821-overview Management of Diarrhea in Patients With HER2-Positive Breast Cancer Treated With Neratinib: A Case Series and Summary of The Literature https://pubmed.ncbi.nlm.nih.gov/34800263/ Pruritus Related to Trastuzumab and Pertuzumab in HER2+ Breast Cancer Patients https://pubmed.ncbi.nlm.nih.gov/37163123/ The Comparative Efficacy and Risk of Harms of the Intravenous and Subcutaneous Formulations of Trastuzumab in Patients With HER2-Positive Breast Cancer: A Rapid Review https://pubmed.ncbi.nlm.nih.gov/31829250/ Overview of Antibody-Drug Conjugates Nonclinical and Clinical Toxicities and Related Contributing Factors https://pubmed.ncbi.nlm.nih.gov/40491603/ Toxicity Profile of Antibody-Drug Conjugates in Breast Cancer: Practical Considerations https://pubmed.ncbi.nlm.nih.gov/37554126/ Oral Mucositis Associated With Antibody-Drug Conjugates in Gynecologic Oncology: Strategies for Prevention and Treatment https://pubmed.ncbi.nlm.nih.gov/40712557/ Incidence of Antibody-Drug Conjugate-Related Hepatotoxicity in Breast Cancer: A Systematic Review and Meta-Analysis https://pubmed.ncbi.nlm.nih.gov/39703774/ T-DM1-Induced Thrombocytopenia in Breast Cancer Patients: New Perspectives https://pubmed.ncbi.nlm.nih.gov/32570117/ Tucatinib vs Placebo, Both in Combination With Trastuzumab and Capecitabine, for Previously Treated ERBB2 (HER2)-Positive Metastatic Breast Cancer in Patients With Brain Metastases: Updated Exploratory Analysis of the HER2CLIMB Randomized Clinical Trial https://pubmed.ncbi.nlm.nih.gov/36454580/ Lung Toxicity Induced by Anti-HER2 Antibody-Drug Conjugates for Breast Cancer https://pubmed.ncbi.nlm.nih.gov/38295890/

Drs Kathy Miller and Sara Tolaney discuss changes in the management of first-line metastatic HER2-positive disease and the DESTINY-Breast09 trial results. Relevant disclosures can be found with the episode show notes on Medscape https://www.medscape.com/viewarticle/1002984. The topics and discussions are planned, produced, and reviewed independently of advertisers. This podcast is intended only for US healthcare professionals. Resources Breast Cancer and HER2 https://emedicine.medscape.com/article/1689966-overview DESTINY-Breast09, New Breakthroughs in First-Line Therapy for HER2-Positive Advanced Breast Cancer https://pubmed.ncbi.nlm.nih.gov/40756960/ Pertuzumab, Trastuzumab, and Docetaxel for HER2-Positive Metastatic Breast Cancer (CLEOPATRA): End-of-Study Results From a Double-Blind, Randomised, Placebo-Controlled, Phase 3 Study https://pubmed.ncbi.nlm.nih.gov/32171426/ Pertuzumab, Trastuzumab, and an Aromatase Inhibitor for HER2-Positive and Hormone Receptor-Positive Metastatic or Locally Advanced Breast Cancer: PERTAIN Final Analysis https://pubmed.ncbi.nlm.nih.gov/36716289/ Trastuzumab Emtansine With or Without Pertuzumab Versus Trastuzumab With Taxane for Human Epidermal Growth Factor Receptor 2-Positive Advanced Breast Cancer: Final Results From MARIANNE https://pubmed.ncbi.nlm.nih.gov/31318460/ Real-World Data on Trastuzumab Emtansine (TDM1) Efficacy and Safety: Results of a Single-Centre Retrospective Study of HER2-Positive Metastatic Breast Cancer Patients https://pubmed.ncbi.nlm.nih.gov/40437155/ Trastuzumab Deruxtecan (T-DXd) + Pertuzumab (P) vs Taxane + Trastuzumab + Pertuzumab (THP) for First-Line (1L) Treatment of Patients (pts) With Human Epidermal Growth Factor Receptor 2–Positive (HER2+) Advanced/Metastatic Breast Cancer (a/mBC): Interim Results From DESTINY-Breast09 https://meetings.asco.org/abstracts-presentations/253126 Randomized, Open Label, Clinical Study of the Targeted Therapy, Palbociclib, to Treat Metastatic Breast Cancer (PATINA) https://www.clinicaltrials.gov/study/NCT02947685 Trastuzumab Deruxtecan Versus Trastuzumab Emtansine in HER2-Positive Metastatic Breast Cancer: Long-Term Survival Analysis of the DESTINY-Breast03 Trial https://pubmed.ncbi.nlm.nih.gov/38825627/ PHESGO Maintenance After T-DXd Short Induction for HER2+ Unresectable Locally Recurrent or Metastatic Breast Cancer (DEMETHER) https://www.clinicaltrials.gov/study/NCT06172127 A Study of Trastuzumab Deruxtecan (T-DXd) Versus Trastuzumab Emtansine (T-DM1) in High-Risk HER2-positive Participants With Residual Invasive Breast Cancer Following Neoadjuvant Therapy (DESTINY-Breast05) https://www.clinicaltrials.gov/study/NCT04622319 Trastuzumab Deruxtecan (T-DXd) Alone or in Sequence With THP, Versus Standard Treatment (ddAC-THP), in HER2-Positive Early Breast Cancer https://clinicaltrials.gov/study/NCT05113251