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.