Introduction
HER2-positive breast cancer occurs in approximately 20% of all breast
cancers, and HER2-targeted therapies, such as trastuzumab and lapatinib,
have shown encouraging efficacy in HER2-positive breast cancer among the
adjuvant and advanced disease settings 1. However,
more than 50% HER2-positive breast cancer patients are inevitable to
generate resistance to the anti-HER2
therapy
ultimately 1. The PI3K/AKT pathway is one of the main
downstream signaling pathways of HER2, and therefore the activation of
the PI3K signaling pathway associates with resistance to HER2-targeted
treatments 2, 3. There is less research that reported
the correlation between PIK3R1 mutation status and the resistance to
HER2-targeted therapy in breast cancer4. PIK3R1
mutations are only found in a small subset (1.8%, 87/4602, TCGA_all
breast cancer studies) of breast cancers5.
Intriguingly, PIK3R1 mutations were more prevalent (17%, 25/147, FUSCC)
in the Chinese cohort 6. Here we describe a
HER2-positive
breast cancer patient
harboring
PIK3R1EY451delinsD who
developed
resistance to HER2-targeted therapy. This provides a novel clue that
PIK3R1EY451delinsD mutation might be clinically useful
to choose the treatment option of everolimus for HER2 positive breast
cancer.
We present the following case in accordance with the CARE reporting
checklist.