Exceptional disease control with neratinib monotherapy in HER2-positive advanced breast cancer: A case report

Human epidermal growth factor receptor 2 (HER2) represents a crucial drug target in breast cancer treatment. Currently, several agents that target HER2 are available, including monoclonal antibodies, antibody-drug conjugates, and tyrosine kinase inhibitors (TKIs). Despite major research efforts, no validated biomarker exists to identify patients who respond to anti-HER2 therapy alone and could be spared the toxicity of chemotherapy. Here we report the case of a 45-years-old patient with recurrent, hormone receptor-positive, and HER2-positive advanced breast cancer who had progressed various lines of treatment but showed an exceptional and prolonged response to neratinib monotherapy. A next-generation sequencing (NGS) analysis on her tumor showed a CDK12-PLXDC1 truncation and amplification of several genes, including CDK12. This case illustrates the activity of neratinib monotherapy and suggests its clinical potential without chemotherapy in a certain subtype of HER2-positive breast cancer, that may possess distinct molecular features, such as CDK12 expression.