Medscape InDiscussion: Breast Cancer and HER2

Drs Kathy Miller and Lajos Pusztai discuss predicting which patients will have a PCR, and the impact this has on new treatments or reducing the intensity of treatments.
Relevant disclosures can be found with the episode show notes on Medscape https://www.medscape.com/viewarticle/1002987. 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
Overall Survival With Pembrolizumab in Early-Stage Triple-Negative Breast Cancer https://pubmed.ncbi.nlm.nih.gov/39282906/
I-SPY 2: A Neoadjuvant Adaptive Clinical Trial Designed to Improve Outcomes in High-Risk Breast Cancer https://pubmed.ncbi.nlm.nih.gov/33312344/
Treatment Efficacy Score-Continuous Residual Cancer Burden-Based Metric to Compare Neoadjuvant Chemotherapy Efficacy Between Randomized Trial Arms in Breast Cancer Trials https://pubmed.ncbi.nlm.nih.gov/35513244/
Predictors of Pathological Complete Response to Neoadjuvant Treatment and Changes to Post-Neoadjuvant HER2 Status in HER2-Positive Invasive Breast Cancer https://pubmed.ncbi.nlm.nih.gov/33526875/
Clinical Decision Impact of HER2DX, an Algorithm-Powered Genomic Diagnostic in Early-Stage HER2-Positive Breast Cancer: Results From a Prospective Real-World Study https://www.sciencedirect.com/science/article/pii/S2949820125000128
Predictive Value of Tumor-Infiltrating Lymphocytes for Neoadjuvant Therapy Response and Prognosis in Breast Cancer: A Multicenter Retrospective Study Based on Chinese Population https://pubmed.ncbi.nlm.nih.gov/41094431/
Predicting Pathologic Complete Response (pCR) From Clinicopathologic Variables and HER2DX Genomic Test in Stage II/III HER2+ Breast Cancer Treated With Taxane, Trastuzumab, and Pertuzumab (THP): Secondary Results From the EA1181/CompassHER2 pCR Trial https://ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.501
MammaPrint Predicts Chemotherapy Benefit in HR+HER2- Early Breast Cancer: FLEX Registry Real-World Data https://pubmed.ncbi.nlm.nih.gov/40796181/
Oncotype DX Breast Recurrence Score®: A Review of Its Use in Early-Stage Breast Cancer https://pubmed.ncbi.nlm.nih.gov/32613290/
Toll-like Receptor-Based Strategies for Cancer Immunotherapy https://pubmed.ncbi.nlm.nih.gov/34124272/
The Tale of TILs in Breast Cancer: A Report From The International Immuno-Oncology Biomarker Working Group https://pubmed.ncbi.nlm.nih.gov/34853355/

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/