May 29, 2020

ASCO 2020: HER2 Reclassification

PUBLICATION: 
ASCO 20

AUTHORS: 
Adam Brufsky, Jennifer A. Crozier, Paul J. Chuba, Sung Ho Lee, Andrea Menicucci, Heather M. Kling, Erin Yoder, William Audeh, FLEX Investigators’ Group

SUMMARY: 

  • Biological heterogeneity of HER2 positive breast cancers is supported by a modest benefit of HER2- targeted therapies reported in the APHINITY and ExteNET trials. This highlights the need for improved biomarkers that more precisely identify patients who benefit from HER2-directed agents.

  • The 80-gene molecular subtyping signature, BluePrint (BP), classifies breast tumors into Luminal, HER2 or Basal subtype based on the gene expression of downstream signaling pathways (1). Previous work showed a substantial proportion of tumors identified as HER2 equivocal or HER2 positive by 2013 ASCO/CAP guidelines may be reclassified as non-HER2 subtype by BP (2).

  • In 2018, ASCO/CAP HER2 IHC/ISH classification guidelines were revised to reduce the frequency of HER2 equivocal cases, for which treatment recommendations have been ambiguous (3). Here we evaluated concordance between HER2 status by 2018 ASCO/CAP guideline classification and BP molecular subtyping.

Read more: ASCO 2020: HER2 Reclassification