Medscape InDiscussion: Breast Cancer and HER2

Drs Kathy Miller and Sunil Badve discuss how HER2 testing has evolved over time as the need for that clinical testing has shifted, including assay limits, biology, and clinical impact.
Relevant disclosures can be found with the episode show notes on Medscape https://www.medscape.com/viewarticle/1002986. 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
Standardized Pathology Report for HER2 Testing in Compliance With 2023 ASCO/CAP Updates and 2023 ESMO Consensus Statements on HER2-Low Breast Cancer https://pubmed.ncbi.nlm.nih.gov/37770765/
Human Epidermal Growth Factor Receptor 2 Testing in Breast Cancer: ASCO-College of American Pathologists Guideline Update https://pubmed.ncbi.nlm.nih.gov/37284804/
Human Breast Cancer: Correlation of Relapse and Survival With Amplification of the HER-2/neu Oncogene https://pubmed.ncbi.nlm.nih.gov/3798106/
Inhibition of Tumor Growth by a Monoclonal Antibody Reactive With an Oncogene-Encoded Tumor Antigen https://pubmed.ncbi.nlm.nih.gov/3466178/
HercepTest https://www.accessdata.fda.gov/cdrh_docs/pdf/P980018S010b.pdf
Effective Extracellular Payload Release and Immunomodulatory Interactions Govern the Therapeutic Effect of Trastuzumab Deruxtecan (T-DXd) https://pubmed.ncbi.nlm.nih.gov/40175391/
Real World Evidence of Neoadjuvant Docetaxel/Carboplatin/Trastuzumab/Pertuzumab (TCHP) in Patients With HER2-Positive Early or Locally Advanced Breast Cancer: A Single-Institutional Clinical Experience https://pubmed.ncbi.nlm.nih.gov/35008143/
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/
Evidence Accumulates Against Sequencing Topo1-ADCs in HER2-Low Metastatic Breast Cancers: Results From International, Retrospective, Real-world ADC-Low-Europe Cohort https://sabcs.multilearning.com/sabcs/2025/eposters/4192135/francois.poumeaud.evidence.accumulates.against.sequencing.topo1-adcs.in.html
Reversal of Tamoxifen Resistant Breast Cancer by Low Dose Estrogen Therapy https://pubmed.ncbi.nlm.nih.gov/15860267/

Drs Kathy Miller and Erika Hamilton discuss ILD linked to ADCs, highlighting early symptoms, key CT findings, pulmonary collaboration, steroid management, and ongoing vigilance.
Relevant disclosures can be found with the episode show notes on Medscape https://www.medscape.com/viewarticle/1002985. 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
Diagnosis and Management of Drug-Induced Interstitial Lung Disease in the Context of Anti-Cancer Therapy: A Multidisciplinary Viewpoint by Portuguese Experts https://pubmed.ncbi.nlm.nih.gov/39500817/
Real-World Perspectives and Practices for Pneumonitis/Interstitial Lung Disease Associated With Trastuzumab Deruxtecan Use in Human Epidermal Growth Factor Receptor 2-Expressing Metastatic Breast Cancer https://pubmed.ncbi.nlm.nih.gov/37207306/
Updates in Drug-Related Pneumonitis Due to Targeted Oncologic Therapies https://pubmed.ncbi.nlm.nih.gov/39524467/
A Review of Treatment-Induced Pulmonary Toxicity in Breast Cancer https://pubmed.ncbi.nlm.nih.gov/34226162/
Detecting and Managing T-DXd-Related Interstitial Lung Disease: The Five "S" Rules https://pubmed.ncbi.nlm.nih.gov/37207309/
Clinical Guidance on the Monitoring and Management of Trastuzumab Deruxtecan (T-DXd)-Related Adverse Events: Insights From an Asia-Pacific Multidisciplinary Panel https://pubmed.ncbi.nlm.nih.gov/37552439/
Neoadjuvant Trastuzumab Deruxtecan Alone or Followed by Paclitaxel, Trastuzumab, and Pertuzumab for High-Risk HER2-Positive Early Breast Cancer (DESTINY-Breast11): A Randomised, Open-Label, Multicentre, Phase III Trial https://pubmed.ncbi.nlm.nih.gov/41130363/
Geyer CE Jr, Park YH, Shao Z, et al; On behalf of the DESTINY-Breast05 investigators. Trastuzumab deruxtecan (T-DXd) vs trastuzumab emtansine (T-DM1) in patients with high-risk human epidermal growth factor receptor 2–positive (HER2+) primary breast cancer with residual invasive disease after neoadjuvant therapy: Interim analysis of DESTINY-Breast05. Presented at: ESMO Congress 2025; October 17-21, 2025; Berlin, Germany https://datasourcebydaiichisankyo.com/documents/d/datahub/lba1_geyer_destiny-breast05-interim-analysis_esmo-2025_oral-presentation_final
Evaluating Risk Factors for Trastuzumab-Deruxtecan Pneumonitis in Patients With Metastatic Breast Cancer https://pubmed.ncbi.nlm.nih.gov/39901280/
CPIC (Clinical Pharmacogenetics Implementation Consortium) https://cpicpgx.org/
Lymphangitic Carcinomatosis https://www.ncbi.nlm.nih.gov/books/NBK560921/

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

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 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/