Nat Commun: HER2-positive breast cancer changes during and after double HER2 blocking.

The HER2 enrichment (HER2-E) subtype in HER2-plus breast cancer is highly dependent on the HER2 pathway.
However, 20-60% of HER2-/HER2-E tumors do not respond fully after anti-HER2 therapy.
here, we evaluated gene expression data before, during and after new auxiliary treatment for HER2-/HER2-E tumors and breast cancer cell lines in the PAMELA trial.
results showed that the double HER2 blocking of HER2-E disease induced low-proliferative Luminal A phenotypes in both tumors and in vitro models in patients.
these biological changes are more pronounced in hormone-receptor-positive (HR-plus) diseases than in HR-negative diseases.
interesting, the use of anti-HER2 therapy increased tumor metatype and increased sensitivity to CDK4/6 inhibition.
finally, stopping HER2 targeted therapy in vitro, or obtaining resistance to HER2 treatment, will lead to the recovery of the original HER2-E phenotype.
in general, the results support the use of maintenance anti-HER2 therapy and the use of CDK4/6 inhibition for subtype switching.
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