The Fellow on Call: The Heme/Onc Podcast Episode 063: Breast Cancer Series, Pt. 8-HER2+, Early Stage Breast Cancer
Jul 5, 2023
Dive into the fascinating world of HER2+ early stage breast cancer. Discover the biology behind HER2 and the groundbreaking origins of trastuzumab. Explore the pivotal trials that highlight the survival benefits of various treatments. Learn about the innovative TCHP regimen and its impact on cardiotoxicity. Uncover management strategies for small tumors and how to approach residual disease with T-DM1. Get equipped with practical algorithms to enhance decision-making in treatment.
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What HER2 Is And How It's Measured
- HER2 is a transmembrane EGFR-family tyrosine kinase that drives aggressive tumor biology when overexpressed.
- Positive is IHC 3+ or FISH ratio >2 (or copy number >6) and predicts recurrence risk and CNS involvement.
Origins Of The HER2 Name
- The HER2 story began in the 1980s with a rat gene called NEU and a homologous human gene on chromosome 17.
- That lineage explains alternate names like HER2, NEU, and ERBB2.
Distinct Mechanisms Of Trastuzumab Vs Pertuzumab
- HER2 activates in a ligand-independent way by homodimerization and heterodimerization with other ERBB receptors to drive PI3K/MAPK signaling.
- Trastuzumab blocks HER2 signaling by binding the receptor, while pertuzumab prevents HER2 heterodimer formation.