HER2-positive breast cancer progresses rapidly after pyrotinib resistance: acquired RET gene fusion and TP53 gene mutation are potential reasons.

Approximately 15-20% of the patients with breast cancer overexpress human epidermal growth factor receptor 2 ( HER2 ). HER2 -positive breast cancer is highly aggressive and has a high relapse rate, suggesting that it is prone to and progresses rapidly after drug resistance. Pyrotinib resistance and changes in patients' conditions after drug resistance are challenging clinical issues and require medical attention. Recently, there are few clinical reports on changes in patients' conditions after pyrotinib resistance. We report a case of a 46-year-old patient with HER2 -positive breast cancer who developed resistance to pyrotinib and rapidly progressed to uncontrolled liver failure in less than a week. To elucidate the cause of the rapid progression, we collected samples of the patient's ascites and performed next-generation sequencing (NGS). On the basis of the NGS results, we speculated that the rapid progression after pyrotinib resistance might be due to RET gene fusion and TP53 gene mutations. Therefore, this case report aims to alert oncologists that patients with HER2 -positive breast cancer, who are resistant to pyrotinib or other targeted drugs, could experience rapid or even flare-up progression and that RET gene fusion and TP53 gene mutations might be potential causes.