A novel mutant PIK3R1 EY451delinsD breast cancer patient resistant to HER2-targeted therapy treated with everolimus: a case report

Background Resistance to HER2-targeted therapy is a critical issue in breast cancer that must be addressed immediately. PIK3R1 mutations are more common in Chinese breast cancer patients (17%, 25/147, Fudan University Shanghai Cancer Center FUSCC vs. 1.8%, 87/4602, TCGA all breast cancer studies). However, very limited information is available on the relationship between PIK3R1 mutation status and resistance to HER2-targeted therapies in patients with HER2-positive breast cancer. Case report We present a case of a HER2-positive advanced breast cancer patient with the PIK3R1 EY451delinsD mutation who developed resistance to HER2-targeted therapy and had a better response to everolimus combined with trastuzumab and carboplatin. Conclusions To the best of our knowledge, this is the first study to show that the PIK3R1 EY451delinsD mutation confers resistance to anti-HER2 therapy in breast cancer and that combining with everolimus treatment may overcome this resistance mechanism. We hypothesize that the PIK3R1 EY451delinsD mutation is associated with the resistance to anti-HER2 therapy, and that this mutation merits further investigation as a clinical biomarker and therapeutic target.