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HER2 Testing in 2023: Case Studies for Pathologists

  • Authors: Giuseppe Viale, MD, FRCPath; Peter A. Fasching, MD
  • CME Released: 3/14/2023
  • Valid for credit through: 3/14/2024
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  • Credits Available

    Physicians - maximum of 1.00 AMA PRA Category 1 Credit(s)™

    You Are Eligible For

    • Letter of Completion

Target Audience and Goal Statement

This educational activity is intended for an international audience of non-US pathologists, hematology/oncology specialists, and obstetricians/gynecologists.

The goal of this activity is to enable learners to increase their knowledge and confidence on HER2 testing considering the recent clinical trial data for HER2-low breast cancer.

Upon completion of this activity, participants will:

  • Have increased knowledge regarding the
    • HER2 testing guidelines and recommendations for breast cancer
    • Definition of HER2-low in breast cancer
  • Have greater competence related to
    • Selecting patients for HER2 testing
  • Demonstrate greater confidence in their ability to
    • Use HER2 testing to drive treatment decisions in advanced breast cancer


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All relevant financial relationships for anyone with the ability to control the content of this educational activity are listed below and have been mitigated. Others involved in the planning of this activity have no relevant financial relationships.

Disclosures for additional planners can be found here.


  • Giuseppe Viale, MD, FRCPath

    Chairman, Department of Pathology & Laboratory Medicine
    European Institute of Oncology
    Milan, Italy


    Guiseppe Viale, MD, FRCPath, has the following relevant financial relationships:
    Consultant or advisor for: Agilent; AstraZeneca; Bayer; Daiichi Sankyo, Inc.; Dako; Menarini; Merck Sharp & Dohme; Novartis; Pfizer, Inc.; Roche; Ventana Medical Systems
    Speaker or member of speakers bureau for: Agilent; Cepheid; Dako; Roche; Ventana Medical Systems
    Research funding from: Roche

  • Peter A. Fasching, MD

    Associate Professor of Gynecology and Obstetrics Translational Medicine
    University Hospital Erlangen
    Comprehensive Cancer Center Erlangen-EMN
    Erlangen, Germany


    Peter A. Fasching, MD, has the following relevant financial relationships:
    Consultant or advisor for: Agendia; AstraZeneca; Daiichi Sankyo, Inc.; Eisai, Inc.; Eli Lilly and Company; Gilead Sciences, Inc.; Merck Sharp & Dohme; Novartis; Pfizer, Inc.; Pierre Fabre; Rocha; Sanofi Aventis; Seagen, Inc.
    Speaker or member of speakers bureau for: AstraZeneca; Daiichi Sankyo, Inc.; Eisai, Inc.; Eli Lilly and Company; Gilead Sciences, Inc.; Merck Sharp & Dohme; Novartis; Pfizer, Inc.; Roche; Seagen, Inc.
    Research funding from: Biontech; Cepheid; Pfizer, Inc.


  • Mihai Surducan, PhD

    Medical Education Director, Medscape, LLC


    Mihai Surducan, PhD, has no relevant financial relationships.

  • Jason Luis Quiñones, PhD

    Associate Medical Writer, Medscape, LLC


    Jason Luis Quiñones, PhD, has no relevant financial relationships.

Compliance Reviewer

  • Esther Nyarko, PharmD

    Director, Accreditation and Compliance, Medscape, LLC


    Esther Nyarko, PharmD, has no relevant financial relationships.

Peer Reviewer

This activity has been peer reviewed and the reviewer has no relevant financial relationships.

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In support of improving patient care, Medscape, LLC is jointly accredited with commendation by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.

    For Physicians

  • Medscape, LLC designates this enduring material for a maximum of 1.0 AMA PRA Category 1 Credit(s)™ . Physicians should claim only the credit commensurate with the extent of their participation in the activity.

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This activity is designed to be completed within the time designated on the title page; physicians should claim only those credits that reflect the time actually spent in the activity. To successfully earn credit, participants must complete the activity online during the valid credit period that is noted on the title page. To receive AMA PRA Category 1 Credit™, you must receive a minimum score of 70% on the post-test.

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HER2 Testing in 2023: Case Studies for Pathologists

Authors: Giuseppe Viale, MD, FRCPath; Peter A. Fasching, MDFaculty and Disclosures

CME Released: 3/14/2023

Valid for credit through: 3/14/2024



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  34. Penault-Llorca F, et al. Experts’ opinion: recommendations for retesting breast cancer metastases for HER2 and hormone receptor status. Breast. 2013;22:200-202.
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  36. Gennari A, et al. ESMO Clinical Practice Guideline for the diagnosis, staging and treatment of patients with metastatic breast cancer. Ann Oncol. 2021;32:1475-1495.
  37. Tarantino P, et al. Evolution of low HER2 expression between early and advanced-stage breast cancer. Eur J Cancer. 2022;163:35-43.
  38. Miglietta F, et al. Evolution of HER2-low expression from primary to recurrent breast cancer. NPJ Breast Cancer. 2021;7:1-8. doi: 10.1038/s41523-021-00343-4. Erratum in: NPJ Breast Cancer. 2021;7:1-8.
  39. Aurilio G, et al. Discordant hormone receptor and human epidermal growth factor receptor 2 status in bone metastases compared to primary breast cancer. Acta Oncol. 2013;52:1649-1656.
  40. Schrijver WA, et al. Receptor conversion in distant breast cancer metastases: a systematic review and meta-analysis, J Natl Cancer Inst. 2018;110:568-580.
  41. Payandeh M, et al. Is there any concordance between of IHC with FISH in HER2-positive breast cancer patients? Int J Hematol Oncol Stem Cell Res. 2015;11:1-6.
  42. Liwski CR, et al. HER2 testing in metastatic breast cancer – Is reflex ISH testing necessary on HER2 IHC-equivocal (2+) cases? Ann Diagn Pathol. 2022;59:1-7.
  43. Memon R, et al. Discordance between immunohistochemistry and in situ hybridization to detect HER2 overexpression/gene amplification in breast cancer in the modern age: a single institution experience and pooled literature review study. Clin Breast Cancer. 2022;22:e123-e133.
  44. Pala EE, et al. Problems in determining HER2 status in breast carcinoma. J Breast Health. 2015;11:10-16.
  45. Orlandi A, et al. To treat or not to treat: HER2 equivocal is the matter! Transl Cancer Res. 2018;S433-S435.
  46. Scheel AH, et al. Physical basis of the ‘magnification rule’ for standardized Immunohistochemical scoring of HER2 in breast and gastric cancer. Diagn Pathol. 2018;13:1-7.
  47. Vance GH, et al. Genetic heterogeneity in HER2 testing in breast cancer. Arch Pathol Lab Med. 2009;133:611-612.
  48. Ahn S, et al. HER2 status in breast cancer: changes in guidelines and complicating factors for interpretation. J Pathology Transl Medicine. 2020;54:34-44.
  49. Fehrenbacher L, et al. NSABP B-47/NRG Oncology phase III randomized trial comparing adjuvant chemotherapy with or without trastuzumab in high-risk invasive breast cancer negative for HER2 by FISH and with IHC 1+ or 2. J Clin Oncol. 2020;38:444-453.
  50. Yazaki S, et al. Lower response to trastuzumab emtansine in metastatic breast cancer patients with human epidermal growth factor receptor 2 immunohistochemistry score of 2 and fluorescence in situ hybridization positive compared with immunohistochemistry score of 3: a retrospective study. Anticancer Drugs. 2020;31:973-978.
  51. Marchiò C, et al. Evolving concepts in HER2 evaluation in breast cancer: heterogeneity, HER2-low carcinomas and beyond. Sem Cancer Bio. 2021;72:123-135.
  52. Sapino A, et al. Current challenges for HER2 testing in diagnostic pathology: state of the art and controversial issues. Front Oncol. 2013;3:1-9.
  53. Venetis K, et al. HER2 low, ultra-low, and novel complementary biomarkers: expanding the spectrum of HER2 positivity in breast cancer. Front Mol Biosci. 2022;9:1-12.
  54. Viale G, et al. Retrospective study to estimate the prevalence and describe the clinicopathological characteristics, treatment patterns, and outcomes of HER2-low breast cancer. Presented at: the San Antonio Breast Cancer Symposium 2022 meeting; December 6-10, 2022; San Antonio, Texas. Poster HER2-15.
  55. Diéras V, et al. Trastuzumab deruxtecan (T-DXd) for advanced breast cancer patients (ABC), regardless HER2 status: a phase II study with biomarkers analysis (DAISY). Cancer Res. 2022;82(Suppl_4): Abstract PD8-02.
  56. Study of trastuzumab deruxtecan (T-DXd) vs investigator’s choice chemotherapy in HER2-low, hormone receptor positive, metastatic breast cancer (DB-06). Accessed December 5, 2022.
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  60. Rugo HS, et al. TROPiCS-02: a phase III study investigating sacituzumab govitecan in the treatment of HR+/HER2- metastatic breast cancer. Future Oncol. 2020;16:705-715.
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  65. Hurvitz SA, et al. Safety and unique pharmacokinetic profile of ARX788, a site-specific ADC, in heavily pretreated patients with HER2-overexpresing solid tumors: Results from two phase 1 clinical trials. J Clin Oncol. 2021;39(suppl 15): Abstract 1038.
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