COR2ED - Oncology Medical Conversation

Metastatic breast cancer: Understanding HER2-low and HER2-ultralow classification

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Understanding HER2-low and HER2-ultralow classification in mBC


In this video podcast moderated by the Oncology Brothers, Dr Komal Jhaveri provides a practical overview of how this shift beyond a binary HER2 model translates into everyday clinical practice.

The experts explore:

  • Key efficacy data from DESTINY-Breast04 and DESTINY-Breast06, and their impact on the HER2 treatment framework
  • The clinical relevance of HER2-low and HER2-ultralow categories, and review the CAP reporting template
  • When and why to perform re-biopsy to detect changes in HER2 expression over time
  • Best practices for monitoring and managing T-DXd–related adverse events, including nausea, vomiting, fatigue and ILD/pneumonitis

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    Watch now to deepen your understanding of HER2-low and HER2-ultralow classification, refine how and when you test, and appreciate the impact on therapeutic decision-making in mBC.

     

    Clinical takeaways

     

    • DESTINY-Breast04 and DESTINY-Breast-06 established T-DXd as an effective option for HER2-low and HER2-ultralow mBC, improving PFS and OS and showing that even minimal HER2 expression can identify patients who benefit from T-DXd
    • Current CAP reporting template separates HER2-low (IHC 1+ or 2+/ISH–) and HER2-ultralow (IHC 0 with faint or incomplete membrane staining in ≤10% of tumour cells) from true HER2-0, creating treatment-defining strata for HER2-targeted ADCs such as T-DXd
    • Because HER2 expression is dynamic between primary and metastatic sites and over time, re-biopsy at progression, particularly in tumours previously scored as HER2-0, should be considered to identify new candidates for T-DXd
    • T-DXd delivers substantial antitumour activity, but treatment-related adverse events, including nausea, vomiting, fatigue, alopecia and, in particular, ILD/pneumonitis, require careful and proactive management. Clinicians should apply structured supportive care and early, vigilant monitoring to ensure safe and sustained treatment

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      This is the full video. Watch the shorter highlights video here: https://youtu.be/3xepcF70Ljw

       

      Listen to the audio version of this conversation on Spotify, Apple, or on the COR2ED website

       

      Follow us on social media:

      LinkedIn: https://www.linkedin.com/company/breastcancerconnect/

      X: https://x.com/BreastCaConnect

       

      This content is intended for healthcare professionals only.

       

      This programme is supported by an Independent Education Grant from AstraZeneca.

      This podcast is developed by cor2ed.com

       

      Published December 2025

       

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      COR2ED - Oncology Medical ConversationBy COR2ED Medical Education