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

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

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

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

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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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