Abstract: Human epidermal growth factor receptor2 (HER2 ) overexpression/amplification is associated with high malignancy, rapid disease progression and poor overall survival in breast cancer. The application of anti-HER2  drugs has greatly improved the survival of patients with HER2 -positive breast cancer, but drug resistance issues affect the long-term efficacy. The HER2  mutation is considered to be one of the reasons for resistance to anti-HER2  therapy, and there is currently no standard treatment. We report for the first time the detection of HER2  amplification with R157W  mutation by second-generation sequencing (NGS) in a 57-year-old hormone receptor-negative, HER2 -positive woman with advanced breast cancer who was resistant to multi-line anti-HER2  therapies. She subsequently received pyrotinib combined with capecitabine treatment and achieved partial response. The small-molecule pan-HER  family irreversible inhibitor pyrotinib combined with capecitabine has shown a promising effect in the treatment of HER2  mutation-induced resistance, but the molecular mechanism and efficacy need to be further verified.
Keywords: breast cancer, HER2 amplification, HER2 R157W mutation, pyrotinib plus capecitabine, anti-HER2 treatment