Decoding the Latest Evidence and Practical Recommendations on Biomarker Testing for New Therapeutic Options Targeting HER2, HER3, and TROP2 in Solid Tumors
Chair, Kurt A. Schalper, MD, PhD, Michael F. Press, MD, PhD, Paolo Tarantino, MD, and Zev A. Wainberg, MD, prepared useful Practice Aids pertaining to immuno-oncology biomarkers for this CME/MOC/CC activity titled “Decoding the Latest Evidence and Practical Recommendations on Biomarker Testing for New Therapeutic Options Targeting HER2, HER3, and TROP2 in Solid Tumors.” For the full presentation, downloadable Practice Aids, and complete CME/MOC/CC information, and to apply for credit, please visit us at https://bit.ly/3iQ5A6Y. CME/MOC/CC credit will be available until April 22, 2022.
Metastatic breast cancer, specifically HER2-positive subtype, represents an advanced stage of breast cancer characterized by the presence of human epidermal growth factor receptor 2 (HER2) overexpression. HER2-positive breast cancer tends to be more aggressive, but advancements in treatment options have significantly improved outcomes.
Targeted therapies play a crucial role in managing metastatic HER2-positive breast cancer. Trastuzumab (Herceptin) and pertuzumab are monoclonal antibodies that specifically target the HER2 protein, inhibiting its activity and impeding cancer cell growth. These drugs are often used in combination with chemotherapy to enhance their effectiveness.
In addition to trastuzumab and pertuzumab, other HER2-targeted therapies such as ado-trastuzumab emtansine (Kadcyla) and lapatinib may be employed in certain cases. Ado-trastuzumab emtansine is an antibody-drug conjugate that delivers chemotherapy directly to HER2-positive cancer cells, minimizing damage to healthy cells. Lapatinib, on the other hand, is a small molecule inhibitor that blocks HER2 and other related receptors.
Given the chronic nature of metastatic breast cancer, treatment plans are often individualized based on the patient's overall health, specific characteristics of the cancer, and prior treatments. Hormone therapy may also be considered if the cancer is hormone receptor-positive. Clinical trials and ongoing research continue to explore novel treatment options, providing hope for further advancements in managing HER2-positive metastatic breast cancer. Patients are encouraged to work closely with their healthcare team to determine the most appropriate and effective treatment plan tailored to their unique circumstances.
Overview of ADC-Based Combination Therapies.pdfDoriaFang
Here we will overview the research progress of ADC-based combination therapies, such as ADC combination with chemotherapy, ADC combination with targeted drugs and ADC combination with immunotherapy.
Metastatic breast cancer, specifically HER2-positive subtype, represents an advanced stage of breast cancer characterized by the presence of human epidermal growth factor receptor 2 (HER2) overexpression. HER2-positive breast cancer tends to be more aggressive, but advancements in treatment options have significantly improved outcomes.
Targeted therapies play a crucial role in managing metastatic HER2-positive breast cancer. Trastuzumab (Herceptin) and pertuzumab are monoclonal antibodies that specifically target the HER2 protein, inhibiting its activity and impeding cancer cell growth. These drugs are often used in combination with chemotherapy to enhance their effectiveness.
In addition to trastuzumab and pertuzumab, other HER2-targeted therapies such as ado-trastuzumab emtansine (Kadcyla) and lapatinib may be employed in certain cases. Ado-trastuzumab emtansine is an antibody-drug conjugate that delivers chemotherapy directly to HER2-positive cancer cells, minimizing damage to healthy cells. Lapatinib, on the other hand, is a small molecule inhibitor that blocks HER2 and other related receptors.
Given the chronic nature of metastatic breast cancer, treatment plans are often individualized based on the patient's overall health, specific characteristics of the cancer, and prior treatments. Hormone therapy may also be considered if the cancer is hormone receptor-positive. Clinical trials and ongoing research continue to explore novel treatment options, providing hope for further advancements in managing HER2-positive metastatic breast cancer. Patients are encouraged to work closely with their healthcare team to determine the most appropriate and effective treatment plan tailored to their unique circumstances.
Overview of ADC-Based Combination Therapies.pdfDoriaFang
Here we will overview the research progress of ADC-based combination therapies, such as ADC combination with chemotherapy, ADC combination with targeted drugs and ADC combination with immunotherapy.
An overview of Clinical Trials for Metastatic HER2-positive Breast Cancer by Dr. Ian Krop, MD, PhD, Chief and Clinical Research Director, Breast Oncology Center at Susan F. Smith Center for Women's Cancers at Dana-Farber Cancer Institute
Despite remarkable progress in the treatment of HER2+ breast cancer, management of this patient population continues to remain a challenge, both in the adjuvant and metastatic settings. An enhanced understanding of the treatment options available for HER2+ breast cancer patients in different settings is imperative to improving patient survival and quality of life. This activity consisting of didactic presentations and case illustrations will address treatment choices for HER2+ patients after trastuzumab progression; proposed mechanisms of resistance; combination treatment approaches; the role of anthracyclines and HER2-targeted agents in this population; and novel targeted agents under investigation, including mTOR inhibitors, antiangiogenic inhibitors, and HER2-targeted therapies.
More information:
http://imeronline.com/867dsd
Review a downloadable slide deck by Kathy D. Miller, MD, covering the most clinically relevant new data reported from Future Directions in the Treatment of Patients With HER2+ Breast Cancer: What Community Oncologists Need to Know.
Target Audience
This activity is designed to meet the educational needs of oncologists and other healthcare professionals involved in cancer care.
Slide Deck Disclaimer
This slide deck in its original and unaltered format is for educational purposes and is current as of September 2012. All materials contained herein reflect the views of the faculty, and not those of IMER, the CME provider, or the commercial supporter. These materials may discuss therapeutic products that have not been approved by the US Food and Drug Administration and off-label uses of approved products. Readers should not rely on this information as a substitute for professional medical advice, diagnosis, or treatment. The use of any information provided is solely at your own risk, and readers should verify the prescribing information and all data before treating patients or employing any therapeutic products described in this educational activity.
Usage Rights
This slide deck is provided for educational purposes and individual slides may be used for personal, non-commercial presentations only if the content and references remain unchanged. No part of this slide deck may be published in print or electronically as a promotional or certified educational activity without prior written permission from IMER. Additional terms may apply. See Terms of Service on IMERonline.com for details.
More information:
http://imeronline.com/867dsd
Antibody–Drug Conjugates for the Treatment of Breast Cancer.pdfDoriaFang
There is a growing number of ADC drugs in development in breast cancer, with no shortage of novel study designs (Table 1.). If these agents continue to show promising activity in early studies, ADC drugs are expected to further transform the breast cancer treatment landscape in the coming years.
In 2009, a 44–year-old female was diagnosed with Hormone
Receptors (HR) positive, HER2-positive, IIA stage, right breast
cancer. After right mastectomy and axillary lymph node dissection, she received adjuvant chemotherapy combined with 1-year
trastuzumab and endocrine therapy with tamoxifen plus goserelin. At the time of completion of 1-year trastuzumab, abdominal
ultrasound revealed liver metastases
Co-Chairs Riad Salem, MD, MBA, and Mark Yarchoan, MD, discuss liver cancer in this CME/MOC activity titled “Establishing the Collaborative Benchmark for HCC Care: Critical Discussions Between Interventional Radiologists and Oncologists to Maximize Therapeutic Benefit.” For the full presentation, downloadable Practice Aids, and complete CME/MOC information, and to apply for credit, please visit us at https://bit.ly/3IOQvQ6. CME/MOC credit will be available until June 14, 2025.
Co-Chairs, Brett Elicker, MD, and David E. Griffith, MD, ATSF, ACCP, OFRSM, prepared useful Practice Aids pertaining to non-cystic fibrosis bronchiectasis for this CME/MOC activity titled “Bridging the Gap to Improved Outcomes in Non-Cystic Fibrosis Bronchiectasis: Ensuring Prompt Diagnosis Through Accurate Interpretation of CT Imaging.” For the full presentation, downloadable Practice Aids, and complete CME/MOC information, and to apply for credit, please visit us at https://bit.ly/48WUULu. CME/MOC credit will be available until June 4, 2025.
More Related Content
Similar to Decoding the Latest Evidence and Practical Recommendations on Biomarker Testing for New Therapeutic Options Targeting HER2, HER3, and TROP2 in Solid Tumors
An overview of Clinical Trials for Metastatic HER2-positive Breast Cancer by Dr. Ian Krop, MD, PhD, Chief and Clinical Research Director, Breast Oncology Center at Susan F. Smith Center for Women's Cancers at Dana-Farber Cancer Institute
Despite remarkable progress in the treatment of HER2+ breast cancer, management of this patient population continues to remain a challenge, both in the adjuvant and metastatic settings. An enhanced understanding of the treatment options available for HER2+ breast cancer patients in different settings is imperative to improving patient survival and quality of life. This activity consisting of didactic presentations and case illustrations will address treatment choices for HER2+ patients after trastuzumab progression; proposed mechanisms of resistance; combination treatment approaches; the role of anthracyclines and HER2-targeted agents in this population; and novel targeted agents under investigation, including mTOR inhibitors, antiangiogenic inhibitors, and HER2-targeted therapies.
More information:
http://imeronline.com/867dsd
Review a downloadable slide deck by Kathy D. Miller, MD, covering the most clinically relevant new data reported from Future Directions in the Treatment of Patients With HER2+ Breast Cancer: What Community Oncologists Need to Know.
Target Audience
This activity is designed to meet the educational needs of oncologists and other healthcare professionals involved in cancer care.
Slide Deck Disclaimer
This slide deck in its original and unaltered format is for educational purposes and is current as of September 2012. All materials contained herein reflect the views of the faculty, and not those of IMER, the CME provider, or the commercial supporter. These materials may discuss therapeutic products that have not been approved by the US Food and Drug Administration and off-label uses of approved products. Readers should not rely on this information as a substitute for professional medical advice, diagnosis, or treatment. The use of any information provided is solely at your own risk, and readers should verify the prescribing information and all data before treating patients or employing any therapeutic products described in this educational activity.
Usage Rights
This slide deck is provided for educational purposes and individual slides may be used for personal, non-commercial presentations only if the content and references remain unchanged. No part of this slide deck may be published in print or electronically as a promotional or certified educational activity without prior written permission from IMER. Additional terms may apply. See Terms of Service on IMERonline.com for details.
More information:
http://imeronline.com/867dsd
Antibody–Drug Conjugates for the Treatment of Breast Cancer.pdfDoriaFang
There is a growing number of ADC drugs in development in breast cancer, with no shortage of novel study designs (Table 1.). If these agents continue to show promising activity in early studies, ADC drugs are expected to further transform the breast cancer treatment landscape in the coming years.
In 2009, a 44–year-old female was diagnosed with Hormone
Receptors (HR) positive, HER2-positive, IIA stage, right breast
cancer. After right mastectomy and axillary lymph node dissection, she received adjuvant chemotherapy combined with 1-year
trastuzumab and endocrine therapy with tamoxifen plus goserelin. At the time of completion of 1-year trastuzumab, abdominal
ultrasound revealed liver metastases
recent advances in chemotherapy of colorectal cancer
Similar to Decoding the Latest Evidence and Practical Recommendations on Biomarker Testing for New Therapeutic Options Targeting HER2, HER3, and TROP2 in Solid Tumors (20)
Co-Chairs Riad Salem, MD, MBA, and Mark Yarchoan, MD, discuss liver cancer in this CME/MOC activity titled “Establishing the Collaborative Benchmark for HCC Care: Critical Discussions Between Interventional Radiologists and Oncologists to Maximize Therapeutic Benefit.” For the full presentation, downloadable Practice Aids, and complete CME/MOC information, and to apply for credit, please visit us at https://bit.ly/3IOQvQ6. CME/MOC credit will be available until June 14, 2025.
Co-Chairs, Brett Elicker, MD, and David E. Griffith, MD, ATSF, ACCP, OFRSM, prepared useful Practice Aids pertaining to non-cystic fibrosis bronchiectasis for this CME/MOC activity titled “Bridging the Gap to Improved Outcomes in Non-Cystic Fibrosis Bronchiectasis: Ensuring Prompt Diagnosis Through Accurate Interpretation of CT Imaging.” For the full presentation, downloadable Practice Aids, and complete CME/MOC information, and to apply for credit, please visit us at https://bit.ly/48WUULu. CME/MOC credit will be available until June 4, 2025.
Co-Chairs, Brett Elicker, MD, and David E. Griffith, MD, ATSF, ACCP, OFRSM, discuss non-cystic fibrosis bronchiectasis in this CME/MOC activity titled “Bridging the Gap to Improved Outcomes in Non-Cystic Fibrosis Bronchiectasis: Ensuring Prompt Diagnosis Through Accurate Interpretation of CT Imaging.” For the full presentation, downloadable Practice Aids, and complete CME/MOC information, and to apply for credit, please visit us at https://bit.ly/48WUULu. CME/MOC credit will be available until June 4, 2025.
Co-Chairs, Jonathan E. McConathy, MD, PhD, and Gil Rabinovici, MD, discuss Alzheimer's disease in this CME/AAPA activity titled “Applying Advances in PET Imaging to Facilitate the Early Diagnosis of Alzheimer’s Disease: Preparing Nuclear Medicine and Radiology Specialists for New Diagnostic Workflows.” For the full presentation, downloadable Practice Aids, and complete CME/AAPA information, and to apply for credit, please visit us at https://bit.ly/45RFl6g. CME/AAPA credit will be available until June 15, 2025.
Co-Chairs Sarah Hayward, PharmD, BCOP, and Ambar Khan, PharmD, BCOP, discuss endometrial and cervical cancers in this CME/CPE/IPCE activity titled “A Pharmacist’s Take on Navigating the Expanding Therapeutic Landscape for Endometrial and Cervical Cancers: Insights on Coordinating and Delivering Effective Modern Care.” For the full presentation, downloadable Practice Aids, and complete CME/CPE/IPCE information, and to apply for credit, please visit us at https://bit.ly/3wGBPQp. CME/CPE/IPCE credit will be available until May 27, 2025.
Co-Chairs, Suzanne Lentzsch, MD, PhD, and Joshua Richter, MD, discuss multiple myeloma in this CME activity titled “‘Four-Ward’ Progress in NDMM: New Developments With CD38 Antibody Quadruplets.” For the full presentation and complete CME information, and to apply for credit, please visit us at https://bit.ly/3x3oWA3. CME credit will be available until May 23, 2025.
Co-Chairs, Jessica Donington, MD, and Jonathan D. Spicer, MD, PhD, FRCSC, prepared useful Practice Aids pertaining to lung cancer for this CME/MOC/AAPA activity titled “Transforming Care and Outcomes With Immunotherapy in Stage I-III Resectable NSCLC: A Case Exploration of New Standards and Emerging Approaches.” For the full presentation, downloadable Practice Aids, and complete CME/MOC/AAPA information, and to apply for credit, please visit us at https://bit.ly/3TxdcP5. CME/MOC/AAPA credit will be available until June 7, 2025.
Co-Chairs, Jessica Donington, MD, and Jonathan D. Spicer, MD, PhD, FRCSC, discuss lung cancer in this CME/MOC/AAPA activity titled “Transforming Care and Outcomes With Immunotherapy in Stage I-III Resectable NSCLC: A Case Exploration of New Standards and Emerging Approaches.” For the full presentation, downloadable Practice Aids, and complete CME/MOC/AAPA information, and to apply for credit, please visit us at https://bit.ly/3TxdcP5. CME/MOC/AAPA credit will be available until June 7, 2025.
Chair Oliver Sartor, MD, discusses prostate cancer in this CME activity titled “On Target: Understanding the Impact of PSMA for Diagnostic and Therapeutic Strategies in Prostate Cancer.” For the full presentation, downloadable Practice Aids, and complete CME information, and to apply for credit, please visit us at https://bit.ly/49oY4IJ. CME credit will be available until May 23, 2025.
Chair and Presenters, Neal D. Shore, MD, FACS, Ashish M. Kamat, MD, MBBS, and Joshua J. Meeks, MD, PhD, prepared useful Practice Aids pertaining to bladder cancer for this CME/MOC/NCPD/AAPA/IPCE activity titled “Harnessing Innovation in Bladder Cancer Care: Strategies for Effectively Implementing Modern Therapeutic Advances Across the Disease Continuum.” For the full presentation, downloadable Practice Aids, and complete CME/MOC/NCPD/AAPA/IPCE information, and to apply for credit, please visit us at https://bit.ly/3PH0RVQ. CME/MOC/NCPD/AAPA/IPCE credit will be available until June 2, 2025.
Chair and Presenters, Neal D. Shore, MD, FACS, Ashish M. Kamat, MD, MBBS, and Joshua J. Meeks, MD, PhD, discuss bladder cancer in this CME/MOC/NCPD/AAPA/IPCE activity titled “Harnessing Innovation in Bladder Cancer Care: Strategies for Effectively Implementing Modern Therapeutic Advances Across the Disease Continuum.” For the full presentation, downloadable Practice Aids, and complete CME/MOC/NCPD/AAPA/IPCE information, and to apply for credit, please visit us at https://bit.ly/3PH0RVQ. CME/MOC/NCPD/AAPA/IPCE credit will be available until June 2, 2025.
Chair, Nicholas J. Short, MD, discusses acute lymphoblastic leukemia in this CME/NCPD/CPE/AAPA/IPCE activity titled “Striking Back at ALL: Achieving Lasting Benefits with Bispecific Antibodies & MRD-Guided Strategies Across Disease Settings.” For the full presentation, downloadable Practice Aids, and complete CME/NCPD/CPE/AAPA/IPCE information, and to apply for credit, please visit us at https://bit.ly/42QsTDT. CME/NCPD/CPE/AAPA/IPCE credit will be available until May 22, 2025.
Chair, Sharon Cohen, MD, FRCPC, prepared useful Practice Aids pertaining to Alzheimer’s disease for this CME/MOC/AAPA activity titled “Specialty Training for the New Era in Alzheimer’s Disease: Building Skills for Making an Early Diagnosis and Implementing Disease-Modifying Treatment.” For the full presentation, downloadable Practice Aids, monograph, and complete CME/MOC/AAPA information, and to apply for credit, please visit us at https://bit.ly/472bp8g. CME/MOC/AAPA credit will be available until May 20, 2025.
Chair, Sharon Cohen, MD, FRCPC, discusses Alzheimer’s disease in this CME/MOC/AAPA activity titled “Specialty Training for the New Era in Alzheimer’s Disease: Building Skills for Making an Early Diagnosis and Implementing Disease-Modifying Treatment.” For the full presentation, downloadable Practice Aids, monograph, and complete CME/MOC/AAPA information, and to apply for credit, please visit us at https://bit.ly/472bp8g. CME/MOC/AAPA credit will be available until May 20, 2025.
Chair and Presenter, Beth Faiman, PhD, MSN, APN-BC, AOCN, BMTCN, FAAN, FAPO, Donna D. Catamero, ANP-BC, OCN, CCRC, and Charise Gleason, MSN, NP-C, AOCNP, discuss multiple myeloma in this CME/MOC/NCPD/ILNA/IPCE activity titled “Ten Steps for Highly Successful Myeloma Care: Guidance on the Road to Remission With Antibodies, BCMA Immunotherapy, and Other Innovations.” For the full presentation, downloadable Practice Aids, and complete CME/MOC/NCPD/ILNA/IPCE information, and to apply for credit, please visit us at https://bit.ly/47mtUnM. CME/MOC/NCPD/ILNA/IPCE credit will be available until May 25, 2025.
Co-Chairs and Presenter Marianne Davies, DNP, ACNP, AOCNP, FAAN, Beth Sandy, MSN, CRNP, FAPO, and Matthew A. Gubens, MD, MS, FASCO, prepared useful Practice Aids pertaining to NSCLC for this CME/MOC/NCPD/ILNA/IPCE activity titled “Making Patient-Centric Immunotherapy a Reality in Lung Cancer: Best Practices for Patient Education, irAE Management, and Survivorship Care.” For the full presentation, downloadable Practice Aids, and complete CME/MOC/NCPD/ILNA/IPCE information, and to apply for credit, please visit us at https://bit.ly/3RDokbZ. CME/MOC/NCPD/ILNA/IPCE credit will be available until May 24, 2025.
Co-Chairs and Presenter Marianne Davies, DNP, ACNP, AOCNP, FAAN, Beth Sandy, MSN, CRNP, FAPO, and Matthew A. Gubens, MD, MS, FASCO, discuss NSCLC in this CME/MOC/NCPD/ILNA/IPCE activity titled “Making Patient-Centric Immunotherapy a Reality in Lung Cancer: Best Practices for Patient Education, irAE Management, and Survivorship Care.” For the full presentation, downloadable Practice Aids, and complete CME/MOC/NCPD/ILNA/IPCE information, and to apply for credit, please visit us at https://bit.ly/3RDokbZ. CME/MOC/NCPD/ILNA/IPCE credit will be available until May 24, 2025.
Co-Chairs, Sia Daneshmand, MD, and Matthew D. Galsky, MD, discuss bladder cancer in this CME/MOC/NCPD/AAPA/IPCE activity titled “Modern Team-Based Therapeutic Management for Bladder Cancer Care: Expert Strategies for Integrating the Latest Evidence and Treatment Advances.” For the full presentation, downloadable Practice Aids, and complete CME/MOC/NCPD/AAPA/IPCE information, and to apply for credit, please visit us at https://bit.ly/3OOeYbO. CME/MOC/NCPD/AAPA/IPCE credit will be available until May 13, 2025.
Chair Jamie Carroll, APRN, CNP, MSN, discusses breast cancer in this NCPD/ILNA/AAPA activity titled “Nurses at the Forefront of Maximizing the Potential of TROP2-Targeted Therapy in TNBC and HR+, HER2- Breast Cancer: Best Practices for Adverse Event Management and Patient Education.” For the full presentation, downloadable Practice Aids, and complete NCPD/ILNA/AAPA information, and to apply for credit, please visit us at https://bit.ly/3SdnvWt. NCPD/ILNA/AAPA credit will be available until May 8, 2025.
Chair Jonathan A. Bernstein, MD, discusses chronic spontaneous urticaria in this CME activity titled “BTK Inhibition Transforming the Landscape of Chronic Spontaneous Urticaria Treatment.” For the full presentation, downloadable Practice Aids, and complete CME information, and to apply for credit, please visit us at https://bit.ly/3P0cnvi. CME credit will be available until May 6, 2025.
More from PVI, PeerView Institute for Medical Education (20)
Ozempic: Preoperative Management of Patients on GLP-1 Receptor Agonists Saeid Safari
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Couples presenting to the infertility clinic- Do they really have infertility...Sujoy Dasgupta
Dr Sujoy Dasgupta presented the study on "Couples presenting to the infertility clinic- Do they really have infertility? – The unexplored stories of non-consummation" in the 13th Congress of the Asia Pacific Initiative on Reproduction (ASPIRE 2024) at Manila on 24 May, 2024.
HOT NEW PRODUCT! BIG SALES FAST SHIPPING NOW FROM CHINA!! EU KU DB BK substit...GL Anaacs
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Title: Sense of Taste
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the structure and function of taste buds.
Describe the relationship between the taste threshold and taste index of common substances.
Explain the chemical basis and signal transduction of taste perception for each type of primary taste sensation.
Recognize different abnormalities of taste perception and their causes.
Key Topics:
Significance of Taste Sensation:
Differentiation between pleasant and harmful food
Influence on behavior
Selection of food based on metabolic needs
Receptors of Taste:
Taste buds on the tongue
Influence of sense of smell, texture of food, and pain stimulation (e.g., by pepper)
Primary and Secondary Taste Sensations:
Primary taste sensations: Sweet, Sour, Salty, Bitter, Umami
Chemical basis and signal transduction mechanisms for each taste
Taste Threshold and Index:
Taste threshold values for Sweet (sucrose), Salty (NaCl), Sour (HCl), and Bitter (Quinine)
Taste index relationship: Inversely proportional to taste threshold
Taste Blindness:
Inability to taste certain substances, particularly thiourea compounds
Example: Phenylthiocarbamide
Structure and Function of Taste Buds:
Composition: Epithelial cells, Sustentacular/Supporting cells, Taste cells, Basal cells
Features: Taste pores, Taste hairs/microvilli, and Taste nerve fibers
Location of Taste Buds:
Found in papillae of the tongue (Fungiform, Circumvallate, Foliate)
Also present on the palate, tonsillar pillars, epiglottis, and proximal esophagus
Mechanism of Taste Stimulation:
Interaction of taste substances with receptors on microvilli
Signal transduction pathways for Umami, Sweet, Bitter, Sour, and Salty tastes
Taste Sensitivity and Adaptation:
Decrease in sensitivity with age
Rapid adaptation of taste sensation
Role of Saliva in Taste:
Dissolution of tastants to reach receptors
Washing away the stimulus
Taste Preferences and Aversions:
Mechanisms behind taste preference and aversion
Influence of receptors and neural pathways
Impact of Sensory Nerve Damage:
Degeneration of taste buds if the sensory nerve fiber is cut
Abnormalities of Taste Detection:
Conditions: Ageusia, Hypogeusia, Dysgeusia (parageusia)
Causes: Nerve damage, neurological disorders, infections, poor oral hygiene, adverse drug effects, deficiencies, aging, tobacco use, altered neurotransmitter levels
Neurotransmitters and Taste Threshold:
Effects of serotonin (5-HT) and norepinephrine (NE) on taste sensitivity
Supertasters:
25% of the population with heightened sensitivity to taste, especially bitterness
Increased number of fungiform papillae
Pulmonary Thromboembolism - etilogy, types, medical- Surgical and nursing man...VarunMahajani
Disruption of blood supply to lung alveoli due to blockage of one or more pulmonary blood vessels is called as Pulmonary thromboembolism. In this presentation we will discuss its causes, types and its management in depth.
New Directions in Targeted Therapeutic Approaches for Older Adults With Mantl...i3 Health
i3 Health is pleased to make the speaker slides from this activity available for use as a non-accredited self-study or teaching resource.
This slide deck presented by Dr. Kami Maddocks, Professor-Clinical in the Division of Hematology and
Associate Division Director for Ambulatory Operations
The Ohio State University Comprehensive Cancer Center, will provide insight into new directions in targeted therapeutic approaches for older adults with mantle cell lymphoma.
STATEMENT OF NEED
Mantle cell lymphoma (MCL) is a rare, aggressive B-cell non-Hodgkin lymphoma (NHL) accounting for 5% to 7% of all lymphomas. Its prognosis ranges from indolent disease that does not require treatment for years to very aggressive disease, which is associated with poor survival (Silkenstedt et al, 2021). Typically, MCL is diagnosed at advanced stage and in older patients who cannot tolerate intensive therapy (NCCN, 2022). Although recent advances have slightly increased remission rates, recurrence and relapse remain very common, leading to a median overall survival between 3 and 6 years (LLS, 2021). Though there are several effective options, progress is still needed towards establishing an accepted frontline approach for MCL (Castellino et al, 2022). Treatment selection and management of MCL are complicated by the heterogeneity of prognosis, advanced age and comorbidities of patients, and lack of an established standard approach for treatment, making it vital that clinicians be familiar with the latest research and advances in this area. In this activity chaired by Michael Wang, MD, Professor in the Department of Lymphoma & Myeloma at MD Anderson Cancer Center, expert faculty will discuss prognostic factors informing treatment, the promising results of recent trials in new therapeutic approaches, and the implications of treatment resistance in therapeutic selection for MCL.
Target Audience
Hematology/oncology fellows, attending faculty, and other health care professionals involved in the treatment of patients with mantle cell lymphoma (MCL).
Learning Objectives
1.) Identify clinical and biological prognostic factors that can guide treatment decision making for older adults with MCL
2.) Evaluate emerging data on targeted therapeutic approaches for treatment-naive and relapsed/refractory MCL and their applicability to older adults
3.) Assess mechanisms of resistance to targeted therapies for MCL and their implications for treatment selection
These lecture slides, by Dr Sidra Arshad, offer a quick overview of physiological basis of a normal electrocardiogram.
Learning objectives:
1. Define an electrocardiogram (ECG) and electrocardiography
2. Describe how dipoles generated by the heart produce the waveforms of the ECG
3. Describe the components of a normal electrocardiogram of a typical bipolar leads (limb II)
4. Differentiate between intervals and segments
5. Enlist some common indications for obtaining an ECG
Study Resources:
1. Chapter 11, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 9, Human Physiology - From Cells to Systems, Lauralee Sherwood, 9th edition
3. Chapter 29, Ganong’s Review of Medical Physiology, 26th edition
4. Electrocardiogram, StatPearls - https://www.ncbi.nlm.nih.gov/books/NBK549803/
5. ECG in Medical Practice by ABM Abdullah, 4th edition
6. ECG Basics, http://www.nataliescasebook.com/tag/e-c-g-basics
Explore natural remedies for syphilis treatment in Singapore. Discover alternative therapies, herbal remedies, and lifestyle changes that may complement conventional treatments. Learn about holistic approaches to managing syphilis symptoms and supporting overall health.
New Drug Discovery and Development .....NEHA GUPTA
The "New Drug Discovery and Development" process involves the identification, design, testing, and manufacturing of novel pharmaceutical compounds with the aim of introducing new and improved treatments for various medical conditions. This comprehensive endeavor encompasses various stages, including target identification, preclinical studies, clinical trials, regulatory approval, and post-market surveillance. It involves multidisciplinary collaboration among scientists, researchers, clinicians, regulatory experts, and pharmaceutical companies to bring innovative therapies to market and address unmet medical needs.
Decoding the Latest Evidence and Practical Recommendations on Biomarker Testing for New Therapeutic Options Targeting HER2, HER3, and TROP2 in Solid Tumors
1. HER2, HER3, and TROP2 as Therapeutic
Targets in Different Cancers
Full abbreviations, accreditation, and disclosure information available at
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HER2 Aberrations: Clinical Role and Frequency Across Tumor Types1,2
•
HER2 is an established therapeutic target in breast and gastric cancer
• HER2 alterations, including overexpression, amplifications, and other mutations, are found in a variety of
other solid tumors as well
•
A number of novel HER2-targeted therapies are being evaluated in breast, gastrointestinal, lung, and other
cancers, indicating that the role and impact of these therapies will continue to expand, along with the need
for broader HER2 testing
ERBB2 amplifications/mutations and HER2 overexpression
have been identified in a range of malignancies
Colorectum
5.8 5 2
Pancreas
2 26 1
Ovary
7 27 1
Prostate
5.8-6 10 1
Tumor types
HER2
amplification (%)
HER2
overexpression (%)
HER2
mutation (%)
Breast
20 15-20 2
Salivary gland
12-52 17-44 1
Stomach
11-16 20 3
Bladder
8.6 12.4 9
Cervix
0.5~14 21 3
Uterus
4-69 18-80 2
Lung
2–3 2.5 1-3
Biliary tract
5-15 20 2
2. HER2, HER3, and TROP2 as Therapeutic
Targets in Different Cancers
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1. Oh DY, Bang YJ. Nat Rev Clin Oncol. 2020;17:33-48. 2. Hechtman JF, Ross DS. Cancer Cytopathol. 2019;127:428-431. 3. Mishra R et al. Oncol Rev. 2018;12:355. 4. Guerra E et al. Oncogene. 2013;32:1594-1600.
5. Zeng P et al. Sci Rep. 2016;6:33658.
Mechanism of Action of Agents Targeting HER21
HER3 and TROP2 as Emerging Therapeutic Targets
a.
Single-epitope monoclonal antibodies bind HER2 at a single extracellular domain, inhibiting downstream
signaling, engaging antibody-dependent cytotoxicity, or inhibiting receptor dimerization
b.
ADCs also have antitumor effects through these pathways, but they additionally exhibit cytotoxicity by
releasing a cytotoxic agent close to HER2-positive tumor cells
c.
Bispecific antibodies target more than one extracellular region of HER2
d.
Small-molecule inhibitors bind the intracellular tyrosine-kinase domain
HER33
•
Crucial heterodimeric partner for other EGFR
family members
•
Potential to regulate EGFR/HER2-mediated
resistance
•
Enhanced expression associated with several
cancers, including lung, breast, ovarian, prostate,
gastric, bladder, melanoma, colorectal, and
squamous cell carcinoma
•
Implicated in contributing to treatment failure
through activation of PI3K/AKT, MAPK/ERK, and
JAK/STAT pathways
•
HER3-targeting investigational therapies:
mono and bispecific antibodies targeting
HER3 at multiple subdomains; miscellaneous
HER3-targeting therapies, including antisense
oligonucleotides, HER3-specific peptide
vaccines, ligand traps, molecules targeting HER3
pseudokinase activity, pan-HER approaches,
HER3 ADCs, and HER3 nanobiologic therapeutic
approaches; select examples: patritumab
deruxtecan/U3-1402 (HER3-targeting ADC) and
MCLA-128 (HER2–HER3 bispecific antibody)
TROP24,5
•
Transmembrane glycoprotein overexpressed in
many different tumors, including lung, breast,
pancreatic, cervical, ovarian, colorectal, and
gastric cancers
•
Membrane bound with an extracellular domain
•
Effectively internalized with binding antibody
•
High expression correlates with poor prognosis
•
Rational therapeutic target; TROP2-targeting
therapies: sacituzumab govitecan/IMMU-132,
datopotamab deruxtecan/DS-1062
Pertuzumab
a. Single-Epitope mAbs b. ADCs
d. Small-Molecule
Inhibitors
c. Bispecific Antibodies
Dimerization
domain
Trastuzumab
Margetuximab
Inhibition of receptor
dimerization
Targeted
delivery of
highly
cytotoxic
agents
Direct inhibition of
the downstream
tyrosine-kinase
domain
Promotion of
receptor
internalization
and/or
degradation
Engagement
of ADCC
Tyrosine-kinase
domain
Cell
membrane
Trastuzumab emtansine
Trastuzumab deruxtecan
Dual targeting of
the trastuzumab
and pertuzumab
binding sites
ZW25
Lapatinib
Neratinib
Tucatinib
I
I
I
III
IV
I
I
I
III
IV
Inhibition of PI3-kinase signalling
promoting cell-cycle arrest
I
I
I
III
IV
3. Treatment Recommendations for HER2+ Breast Cancer
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a
Alternative taxanes (ie, docetaxel, paclitaxel, albumin-bound paclitaxel) may be substituted for select patients due to medical necessity (ie, hypersensitivity reaction). If substituted for weekly paclitaxel or docetaxel, then the weekly dose of albumin-bound paclitaxel should not
exceed 125 mg/m2
. b
Paclitaxel + trastuzumab may be considered for patients with low-risk T1, N0, M0, HER2+ disease, particularly those not eligible for other standard adjuvant regimens due to comorbidities. c
Trastuzumab given in combination with an anthracycline is associated
with significant cardiac toxicity. Concurrent use of trastuzumab and pertuzumab with an anthracycline should be avoided. d
Consider extended adjuvant neratinib following adjuvant trastuzumab-containing therapy for patients with HR+/HER2+ with a perceived high risk of
recurrence. The benefit or toxicities associated with extended neratinib in patients who have received pertuzumab or ado-trastuzumab emtansine is unknown. e
It is acceptable to change the administration sequence to taxane (with or without HER2-targeted therapy) followed by AC.
1. NCCN Clinical Practice Guidelines in Oncology. Breast Cancer. Version 1.2022. https://www.nccn.org/professionals/physician_gls/pdf/breast.pdf.
Preferred Regimens
• Paclitaxel + trastuzumabb
• TCH (docetaxel/carboplatin/trastuzumab)
• TCHP (docetaxel/carboplatin/trastuzumab/pertuzumab)
• If no residual disease after preoperative therapy or no preoperative therapy: complete up to 1 year of HER2-targeted
therapy with trastuzumabc
(category 1) ± pertuzumab
• If residual disease after preoperative therapy: trastuzumab emtansine (category 1) alone; if trastuzumab emtansine
discontinued for toxicity, then trastuzumab (category 1) ± pertuzumab to complete 1 year of therapyc,d
Useful in Certain Circumstances Other Recommended Regimens
• Docetaxel + cyclophosphamide + trastuzumab
• AC followed by Te
+ trastuzumabc
(doxorubicin/cyclophosphamide followed by paclitaxel +
trastuzumab; various schedules)
• AC followed by Te
+ trastuzumab + pertuzumabc
(doxorubicin/cyclophosphamide followed by paclitaxel +
trastuzumab + pertuzumab; various schedules)
• Neratinibd
(adjuvant setting only)
• Paclitaxel + trastuzumab + pertuzumabc
• Trastuzumab emtansine (adjuvant setting only)
• AC followed by docetaxele
+ trastuzumabc
(doxorubicin/cyclophosphamide followed by docetaxel +
trastuzumab)
• AC followed by docetaxele
+ trastuzumab + pertuzumabc
(doxorubicin/cyclophosphamide followed by docetaxel +
trastuzumab + pertuzumab)
Preoperative/Adjuvant Therapy: Updated Recommendations Based on NCCN Guidelines Version 1.20221,a
Updates in Version 1.2022 of the Guidelines From Version 8.2021
Useful in certain circumstances, options added:
• Neratinib (adjuvant setting only)
• Paclitaxel + trastuzumab + pertuzumab
• Trastuzumab emtansine (adjuvant setting only)
!
4. Treatment Recommendations for HER2+ Breast Cancer
Full abbreviations, accreditation, and disclosure information available at PeerView.com/EZK40
a
Maintenance trastuzumab/pertuzumab after response (with concurrent endocrine therapy if ER+ and HER2+ metastatic breast cancer). b
Regimens may also be used as an option for third line and beyond; the optimal sequence for third-line therapy and beyond is not known.
c
An FDA-approved biosimilar is an appropriate substitute for trastuzumab. d
Trastuzumab deruxtecan may be considered in the first-line setting as an option for select patients (ie, those with rapid progression within 6 months of neoadjuvant or adjuvant therapy [12 months for
pertuzumab-containing regimens]). e
Trastuzumab deruxtecan is contraindicated for patients with pneumonitis or ILD. f
Tucatinib + trastuzumab + capecitabine is preferred in patients with both systemic and CNS progression in the third-line setting and beyond and it may be given
in the second-line setting. g
Multiple lines of concurrent chemotherapy with anti-HER2 therapy (trastuzumab or a TKI) offer clinical benefit for recurrent unresectable HER2+ metastatic breast cancer and have been studied in phase 2 or 3 trials. Clinical experience suggests frequent
clinical benefit for such treatment. However, there are no meaningful data for use of any of these regimens among patients previously treated with pertuzumab-based chemotherapy, trastuzumab emtansine, trastuzumab deruxtecan, or trastuzumab/capecitabine/tucatinib regimens.
Thus, the optimal sequence or true benefit of therapy is not known. h
Trastuzumab given in combination with an AC is associated with significant cardiac toxicity. Concurrent use of trastuzumab and pertuzumab with an AC should be avoided. i
Trastuzumab may be safely combined
with all non−AC-containing preferred and other single agents listed on the NCCN guidelines for systemic therapies for recurrent or metastatic breast cancer (BINV-Q [1 of 8]).
1. NCCN Clinical Practice Guidelines in Oncology. Breast Cancer. Version 1.2022. https://www.nccn.org/professionals/physician_gls/pdf/breast.pdf.
Updates in Version 1.2022 of the Guidelines From Version 8.2021
• Second-line option added: Trastuzumab deruxtecan; this is a category 1 preferred regimen
• Second-line option modified: Trastuzumab emtansine has been changed from a category 1 preferred regimen to a category 2A other recommended regimen
•
Heading modified: Third line and beyond (optimal sequence is not known)
Recurrent Unresectable (Local or Regional) or Stage IV (M1) Disease: Updated Recommendations Based on NCCN
Guidelines Version 1.20221
Setting Regimen NCCN Category of Preference Evidence Level
First linea
Pertuzumab + trastuzumab + docetaxelc Preferred regimen 1
Pertuzumab + trastuzumab + paclitaxelc Preferred regimen 2A
Second lineb
Trastuzumab deruxtecan (T-DXd)b,d,e Preferred regimen 1
Trastuzumab emtansine (T-DM1)b Other recommended regimen 2A
Third line and
beyond
(optimal sequence
unknown)
Tucatinib + capecitabine + trastuzumabc,f Other recommended regimen 1
Trastuzumab + docetaxel or vinorelbinec,g Other recommended regimen 2A
Trastuzumab + paclitaxel ± carboplatinc,g Other recommended regimen 2A
Capecitabine + trastuzumab or lapatinibc,g Other recommended regimen 2A
Trastuzumab + lapatinibc,g (without cytotoxic therapy) Other recommended regimen 2A
Trastuzumab + other agentsc,g,h,i Other recommended regimen
Neratinib + capecitabineg Other recommended regimen 2A
Margetuximab + chemotherapyg (capecitabine, eribulin, gemicitabine, or vinorelbine) Other recommended regimen 2A
2A
•
Footnote b modified: Regimens may also be used as an option for third line and beyond or fourth-line option; the optimal sequence for third-line therapy and beyond is not known
• Footnote d added: Trastuzumab deruxtecan may be considered in the first-line setting as an option for select patients (ie, those with rapid progression within 6 months of
neoadjuvant or adjuvant therapy [12 months for pertuzumab-containing regimens])
• Footnote f modified: Tucatinib + trastuzumab + capecitabine is preferred in patients with both systemic and CNS progression in the third-line setting and beyond
on trastuzumab emtansine. However, tucatinib + trastuzumab + capecitabine and it may be given in the second-line setting
•
Footnote removed: Trastuzumab deruxtecan is preferred in patients with visceral metastases if progression on trastuzumab emtansine
!
5. Testing for HER2 and HER2-Low
Expression in Breast Cancer
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Must order reflex test
(same specimen using ISH)
or order a new test
(new specimen if available,
using IHC or ISH)
IHC 3+
positive
IHC 1+
negative
IHC 0
negative
No staining is observed
or
Membrane staining that
is faint/barely perceptible
and in ≤10% of tumor cells
IHC 2+
equivocal
Batch controls and on-slide controls show appropriate staining
Incomplete membrane
staining that is faint/barely
perceptible and in
10% of tumor cells
Weak-to-moderate
complete membrane
staining observed in
10% of tumor cells
Circumferential membrane
staining that is complete,
intense, and in
10% of tumor cells
HER2 testing (invasive component) by validated IHC assay
• HER2 IHC 2+ (equivocal) cases with “weak-to-moderate complete membrane staining” observed in 10% of tumor cells
• If the initial HER2 test result in a core needle biopsy is negative, may repeat test in excision specimen based on clinical criteria
• If HER2/CEP17 ratio of ≥2.0, but the average HER2 signals per cell is 4.0, additional workup is needed
• If average of ≥6.0 HER2 signals per cell with an HER2/CEP17 ratio 2.0 (formerly diagnosed as ISH positive for HER2),
additional workup is needed
• If average HER2 signals per tumor cell ≥4.0 and 6.0 and the HER2/CEP17 ratio is 2.0 (formerly diagnosed as ISH equivocal),
additional workup is needed
Updates in the 2018 ASCP/CAP Guidelines1
Recommendations by the ASCO/CAP HER2 Testing Expert Panel are aimed at
improving the analytic validity of HER2 testing and the clinical utility of HER2 as a
predictive biomarker for potential responsiveness to therapies targeting the HER2 protein.
HER2 gene amplification assessed by in situ hybridization (ISH) or protein
overexpression assessed by IHC remains the primary predictor of responsiveness
to HER2-targeted therapies in breast cancer.
Breast Cancer: 2018 ASCO/CAP Guidelines for
Evaluation of HER2 Protein Expression by IHC1
6. Testing for HER2 and HER2-Low
Expression in Breast Cancer
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ISH
positive
ISH
negative
Evaluation of HER2 Gene Amplification
by ISH Assay Using Dual-Probe ISH¹
Additional
workup required
Additional
workup required
Additional
workup required
HER2 testing (invasive component) by validated dual-probe ISH assay
Evaluation of HER2 Gene Amplification
by ISH Assay Using Single-Probe ISH¹
HER2/CEP17
ratio ≥2.0
HER2/CEP17
ratio 2.0
Group 1
Average HER2
copy number
≥4.0 signals/cell
Group 2
Average HER2
copy number
4.0 signals/cell
Group 3
Average HER2
copy number
≥6.0 signals/cell
Group 4
Average HER2 copy
number ≥4.0 and
6.0 signals/cell
Group 5
Average HER2
copy number
4.0 signals/cell
Batch controls and on-slide controls show appropriate hybridization
ISH
positive
ISH
negative
Average HER2 copy number
≥6.0 signals/cell
Average HER2 copy number
4.0 signals/cell
Concurrent IHC 3+
and/or
Concurrent dual-probe
ISH group 1
Concurrent IHC 0, 1+
and/or
Concurrent dual-probe
ISH group 5
Batch controls and on-slide controls show appropriate hybridization
Average HER2 copy number
≥4.0 and 6.0 signals/cell
Perform dual-probe
ISH for final result
Concurrent
IHC 2+
HER2 testing (invasive component) by validated single-probe ISH assay
7. Testing for HER2 and HER2-Low
Expression in Breast Cancer
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Summary of the Major Changes in the ASCO/CAP HER2 Testing Guidelines Between 2007 and 2018²
HER2 testing must be performed on
all newly diagnosed and recurrent
breast cancers
Re-emphasized the importance of
testing metastatic breast cancers
At least one HER2 test should
be performed on primary and
metastatic breast cancers
Specimen type Same as 2013
Homogeneous, dark circumferential
membrane staining in 10% of
invasive tumor cells
Homogeneous, dark circumferential
membrane staining in 30% of
invasive tumor cells
IHC positive
HER2 (3+)
Same as 2013
• 0: No staining or incomplete
membranous staining that is
faint/barely perceptible and within
≤10% of invasive tumor cells
• 1+: Incomplete membranous
staining that is faint/barely
perceptible and within 10% of
invasive tumor cells
• 0: No staining
• 1+: Weak incomplete
membrane staining in any
proportion of tumor cells or
weak, complete membrane
staining in 10%
IHC negative
HER2 (0 or 1+) Same as 2013
• Single probe: HER2 copy number
≥4.0 and 6 signals/cell
• Dual probe: HER2/CEP17 ratio
of 2.0 with an average HER2
copy number ≥4.0 and
6 signals/cell
HER2/CEP17 ratio of 1.8-2.2 or
average HER2 gene copy number
4-6 signals/nucleus for test without
an internal control probe
ISH equivocal
Need additional work concomitant
with IHC result to render a
diagnosis whether HER2 is positive
or negative, with an explanatory
comment to be added
Must repeat if:
• Tumor on excision is grade 3
• Invasive tumor in the NCB is small
• Resection specimen contains high-grade
carcinoma that is morphologically distinct
from the prior core
• Core biopsy result is equivocal for HER2
after testing by both ISH and IHC
• There is doubt about the specimen
handling of the core biopsy (long ischemic
time, short time in fixative, different fixative)
or the test is suspected by the pathologist
to be negative on the basis of testing error
No recommendations
NCB negative
Same as 2013 but change
the word “must” to “may”
2013
2007
Item 2018
Circumferential membrane staining
that is incomplete and/or
weak/moderate and with 10% of
invasive tumor cells
Complete and circumferential
membranous staining that is
intense and within ≤10% of
invasive tumor cells
Non-uniform or weak intensity,
circumferential, complete
membranous staining in at
least 10% of invasive tumor cells
Complete and intense membranous
staining of 30% or less of
invasive tumor cells
Complete weak/moderate
membrane staining in 10%
of invasive tumor cells
Complete and circumferential
membranous staining that is
intense and within ≤10% of
invasive tumor cells
• Single probe: HER2 copy number
4.0 signals/cell
• Dual probe: HER2/CEP17 ratio
of 2.0 with an average HER2
copy number 4.0 signals/cell
HER2/CEP17 ratio of 1.8 or
average HER2 gene copy number
4 signals/nucleus for test without
an internal control probe
Same as 2013
IHC equivocal
HER2 (2+)
No specification on the type of
the probe (whether single or dual)
for test without an internal control
probe
• HER2 to CEP17 ratio of 2.2
or average HER2 gene copy
number 6 signals/nucleus
ISH positive
Same as 2013 for group 1
Groups 2 and 3: Need additional
work concomitant with IHC result
to render a diagnosis whether
HER2 is positive or negative,
with an explanatory comment
to be added
Specified criteria for single and
dual probe:
• Group 1: Single-probe average HER2
copy number ≥6.0 signals/cell or dual-probe
HER2/CEP17 ratio of ≥2.0 with an average
HER2 copy number ≥4.0 signals/cell
• Group 2: Dual-probe HER2/CEP17
ratio of ≥2.0 with an average HER2
copy number 4.0 signals/cell
• Group 3: Dual-probe HER2/CEP17
ratio of 2.0 with an average HER2
copy number ≥6.0 signals/cell
ISH negative
6-72 h
6-48 h Same as 2013
Duration of
tissue fixation
8. Testing for HER2 and HER2-Low
Expression in Breast Cancer
Full abbreviations, accreditation, and disclosure information available at
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Going Beyond the Dichotomous
HER2+/- Status?
Proposed Algorithm for Defining
HER2-Low Breast Cancer4
HER2 positive HER2 low HER2 negative
Reflex
ISH test
positive
Reflex
ISH test
negative
Circumferential membrane
staining that is complete,
intense, and in
10% of tumor cells
IHC 3+
Weak-to-moderate
complete membrane
staining in
10% of tumor cells
IHC 2+
Incomplete membrane
staining that is faint/barely
perceptible and in
10% of tumor cells
IHC 1+
No staining is observed:
HER2 null
or
Membrane staining that
is incomplete and is
faint/barely perceptible
and in10% of tumor cells
IHC 0+
HER2 testing by
validated IHC assay
HER2 positive
HER2 negative
Dichotomous
HER2 positive
HER2 negative
HER2 low
New
paradigm?
Challenge: Distinguishing IHC score 0 from score 1+
HER-low BC: ≈55%
• IHC 1+, IHC 2+ with
a negative ISH test
HER2-positive BC: ≈15%
HER2-negative BC: ≈30%
International guidelines currently recommend a binary model (HER2 positive vs negative) to guide
clinicians in treatment decisions. However, a great proportion of patients (≈40%-55%) classified as HER2
negative are, in fact, HER2 low; a population with a high unmet medical need. Despite past drawbacks
with older drugs, a new generation of anti-HER2 agents has recently shown encouraging signs of clinical
activity and safety in HER2-low disease.3
9. Testing for HER2 and HER2-Low
Expression in Breast Cancer
Full abbreviations, accreditation, and disclosure information available at
PeerView.com/EZK40
1. Wolff AC et al. Arch Pathol Lab Med. 2018;142:1364-1382. 2. Zhang H et al. Curr Oncol Rep. 2020;22:51. 3. Eiger D et al. Cancers (Basel). 2021;13:1015. 4. Tarantino P et al. J Clin Oncol. 2020;38:1951-1962.
Novel Agents and Mechanisms Enabling the Targeting of HER2-Low Breast Cancer4
Th1
Vaccines
Bispecific Antibodies
Antibody–Drug Conjugates
Monoclonal
Antibodies
Trastuzumab
Margetuximab
Pertuzumab
RAF/MEK/MAPK
Proliferation
PI3K/AKT/mTOR
Survival
Trastuzumab
Pertuzumab
Margetuximab
TrasGEX
Trastuzumab deruxtecan
Trastuzumab duocarmazine
PF-06804103
A166
RC48-ADC
ARX788
Antitumoral
agent
Linker
Antibody
Proliferation
Survival
MCLA-128
ZW25
Ertumaxomab
MM-111
GBR 1302
Nelipepimut-S
GP2
AE37
CTL
MHC I
TNFα
IFNγ
HER2-
polarized
DC
Novel anti-HER2 drugs enable the targeting of low HER2-expressing cancers through different mechanisms: A. Monoclonal antibodies engineered to enhance
antibody-dependent cellular cytotoxicity, or to more effectively inhibit HER2 heterodimerization, have shown preclinical evidence of activity in HER2-low breast
cancer. B. Novel antibody–drug conjugates enable exploitation of low HER2 expression to direct cytotoxic molecules to tumor cells, showing promising activity
in early clinical trials. C. Bispecific antibodies allow forced connections between cancer and immune cells and/or suppress multiple signaling pathways, with
potential activity in HER2-low breast cancer cells. D. Cancer vaccines enhance antitumor immune response against HER2 and are currently being tested in
the adjuvant setting to reduce relapses in HER2-low breast cancer.
A B C D
10. HER2 Testing in Gastroesophageal Cancer
Guidance From CAP/ASCP/ASCO1
Full abbreviations, accreditation, and disclosure information available at PeerView.com/EZK40
GEA and potential
candidate for
HER2-targeted
therapy
HER2-targeted therapy should not
be initiated until HER2 positivity
is confirmed
Biopsy or resection specimen
from primary or metastatic sites
should be used
Alternative: FNA specimens
(cell blocks) may be used
Request
HER2 test
Equivocal
or negative
result
Inadequate
specimen
tested
No positive
results
Positive
results
Initiate HER2-targeted therapy;
no further HER2 testing is
required
Retest additional available
tissue; if there is no available
tissue, additional tumor tissue
may be obtained for retesting
NGS2
enables assessment
of ERBB2 copy number
and mutations simultaneously,
along with other molecular
events such as TMB
and MSI status; can be performed
on both surgical specimens
or cell blocks and has recently
been shown to work
with cytologic
supernatant
11. HER2 Testing in Gastroesophageal Cancer
Guidance From CAP/ASCP/ASCO1
Full abbreviations, accreditation, and disclosure information available at PeerView.com/EZK40
Perform HER2
test using
IHC
IHC 2+
Equivocal
IHC 1+
Negative
IHC 3+
Positive
Perform ISH
Testing
IHC 0
Negative
Surgical specimen
Strong, complete basolateral or
lateral membranous reactivity in
≥10% of tumor cells
Biopsy specimen
Tumor cell cluster with strong,
complete basolateral or lateral
membranous activity irrespective
of percentage of tumor cells
stained
Surgical specimen
Weak to moderate, complete
basolateral or lateral membranous
reactivity in ≥10% of tumor cells
Biopsy specimen
Tumor cell cluster with weak/
moderate, complete basolateral
or lateral membranous activity
irrespective of percentage of
tumor cells stained
Surgical specimen
Faint/barely perceptible
membranous reactivity in ≥10% of
tumor cells; cells reactive only in
part of their membrane
Biopsy specimen
Tumor cell cluster with faint/barely
membranous activity irrespective
of percentage of tumor cells
stained
Surgical specimen
No reactivity or membranous
reactivity in 10% of tumor cells
Biopsy specimen
No reactivity in any tumor cells
No further ISH testing is required No further ISH testing is required
Tissue sample
from patient
diagnosed
with GEA
12. HER2 Testing in Gastroesophageal Cancer
Guidance From CAP/ASCP/ASCO1
Full abbreviations, accreditation, and disclosure information available at PeerView.com/EZK40
1. Bartley AN et al. Am J Clin Pathol. 2016;146:647-669. 2. Hechtman JF, Ross DS. Cancer Cytopathol. 2019;127:428-431.
Summary of HER2 Testing Recommendations
Strength of Recommendation
Strong recommendation • In patients with GEA who are potential candidates for HER2-targeted therapy, the treating clinician should request HER2 testing on tumor tissue
Strong recommendation
• Laboratories must incorporate GEA HER2 testing methods into their overall laboratory quality improvement program, establishing appropriate quality improvement
monitors as needed to ensure consistent performance in all steps of the testing and reporting process; in particular, laboratories performing GEA HER2 testing must
participate in a formal proficiency testing program, if available, or an alternative proficiency assurance activity
• Laboratories should report HER2 testing results in GEA specimens in accordance with the CAP “Template for Reporting Results of HER2 (ERBB2) Biomarker Testing
of Specimens From Patients With Adenocarcinoma of the Stomach or Esophagogastric Junction”
Strong recommendation
Strong recommendation
• Pathologists should identify areas of invasive adenocarcinoma and also mark areas with the strongest intensity of HER2 expression by IHC in GEA specimens for
subsequent ISH scoring when required
Recommendations
No recommendation • There is insufficient evidence to recommend for or against genomic testing in patients with GEA at this time
Strong recommendation
• When GEA HER2 status is being evaluated, laboratories/pathologists should perform/order IHC testing first, followed by ISH when IHC result is 2+ (equivocal);
positive (3+) or negative (0 or 1+) HER2 IHC results do not require further ISH testing
• Pathologists should select the tissue block with the areas of lowest grade tumor morphology in biopsy and resection specimens; more than 1 tissue block may be
selected if different morphologic patterns are present
Recommendation
• Pathologists should use the Ruschoff/Hofmann method in scoring HER2 IHC and ISH results for GEA
Strong recommendation
Strong recommendation
• Laboratories/pathologists must specify the antibodies and probes used for the test and ensure that assays are appropriately validated for HER2 IHC and ISH on
GEA specimens
Recommendation
• Treating clinicians should offer combination chemotherapy and HER2-targeted therapy as the initial treatment for appropriate patients with HER2-positive tumors
who have metastatic or recurrent GEA
Recommendation
• Treating clinicians or a pathologist should request HER2 testing on tumor tissue in the biopsy or resection specimens (primary or metastasis), preferably before the
initiation of trastuzumab therapy if such specimens are available and adequate; HER2 testing on FNA specimens (cell blocks) is an acceptable alternative
13. HER2, HER3, and TROP2 as Therapeutic
Targets in Lung Cancer
Full abbreviations, accreditation, and disclosure information available at
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•
HER2 is overexpressed, amplified, or mutated in a
significant fraction of lung adenocarcinomas, but
prognostic significance is not yet fully defined
–
Frequency of overexpression (IHC 2+ and 3+): 15%-30%
– Frequency of overexpression (IHC 3+): 2%-6%
– Frequency of amplification: 2%-6%
– Frequency of mutations: 1%-5%
•
HER2 dysregulations encompass heterogeneous
and distinct alterations which must be taken into
consideration
–
There is a lack of correlation between overexpression,
amplification, and mutations
–
Cohorts must be defined according to the specific HER2
alteration present
•
The appropriate testing methodology for different HER2
alterations should be used
– Amplification: in situ hybridization (ISH)
– Expression: immunohistochemistry (IHC)
– Mutation: sequencing (NGS or other)
•
Although they have become outdated in the context of
the rapid advances in targeted therapy for lung cancer
and related biomarker testing demands, the latest
published lung cancer molecular testing guidelines state
that HER2 molecular testing is not indicated as a routine
stand-alone assay to guide targeted therapy selection
outside the context of a clinical trial. However, it is
appropriate to include HER2 mutation analysis as part of
a larger testing panel performed either initially or when
routine testing results for other alterations with approved
targeted therapies are negative.
•
There is a rationale for investigating HER2-targeted
therapies in NSCLC
•
Antibody–drug conjugates (ADCs) represent a promising
therapeutic approach; agents under investigation
include:
–
Trastuzumab deruxtecan (T-DXd)—in various settings
of HER2-expressing and HER2-mutated NSCLC
– Ado-trastuzumab emtansine (T-DM1)
• HER3 is highly expressed in NSCLC
•
HER3 overexpression is associated with metastatic
progression and poor outcomes in patients with NSCLC
•
There are currently no established biomarker testing
recommendations for HER3 in NSCLC
•
HER3 alterations are not known to be a mechanism of
resistance to EGFR TKIs in EGFR-mutated NSCLC
•
Targeting HER3 may address multiple EGFR-targeted
therapy resistance mechanisms
•
There is a rationale for investigating HER3-targeted
therapies in NSCLC
•
ADCs represent a promising therapeutic approach: eg,
anti-HER3 ADC patritumab deruxtecan
(HER3-DXd) is under investigation in various
settings of EGFR-mutated advanced NSCLC
HER1 HER2 HER3 HER4
EGFR family
Cytoplasm
Nucleus
Chr17
HER2
• Proliferation
• Motility
• Invasiveness
• Survival
• Angiogenesis
P P
PI3K
Akt
SOS
RAS
RAF
MEK
MAPK
P
P
Ligands
Role of HER2 in NSCLC1-7
Role of HER3 in NSCLC8
14. HER2, HER3, and TROP2 as Therapeutic
Targets in Lung Cancer
Full abbreviations, accreditation, and disclosure information available at
PeerView.com/EZK40
Role of TROP2 in NSCLC9-12
•
TROP2 is highly expressed in NSCLC and has been
associated with poor prognosis
•
There are currently no established biomarker testing
recommendations for TROP2 in NSCLC
•
There is a rationale for investigating TROP2-targeted
therapies in NSCLC
•
ADCs represent a promising therapeutic approach:
eg, the anti-TROP2 ADC datopotamab deruxtecan
(Dato-DXd) is under investigation in various settings
of NSCLC with and without actionable genomic
alterations
1. Li BT et al. J Thorac Oncol. 2016;11:414-419. 2. Li BT et al. International Association for the Study of Lung Cancer 18th World Conference on Lung Cancer (WCLC 2017). Abstract OA14.05. 3. Li BT et al.
J Clin Oncol. 2018;36:2532-2537. 4. Iqbal N et al. Mol Biol Int. 2014;2014:852748. 5. Yan M et al. Cancer Metastasis Rev. 2015;34:157-164. 6. Rolfo C et al. Cancer Discov. 2020;10:643-645. 7. Lindeman NI et al.
Arch Pathol Lab Med. 2018;142:321-346. 8. Scharpenseel H et al. Sci Rep. 2019;9:7406. 9. Mito R et al. Pathol Int. 2020;70:287-294. 10. Inamura K et al. Oncotarget. 2017;8:28725-28735. 11. Jiang A et al.
Oncol Lett. 2013;6:375-380. 12. Lenart S et al. Cancers (Basel). 2020;12:3328.
Fibronectin
Decreased adhesion
Increased cell migration
ErB3 activation
NRG-1 is released
when TROP2 is lost
Recruitment to
tight junctions
NRG-1
TACE
Clauidn 1/7
TROP2
α5 β1
Talin
RACK 1
RACK 1
FAK
P
FAK
Src
Src
P
NRG-1
Endosome