After endocrine therapy and CDK4/6 inhibitor treatment, the patient's disease still progressed and transformed into triple-negative BC.<h4>Diagnoses</h4>Peripheral blood circulating tumor cells were isolated from the patient and performed targeted sequencing by using next-generation sequencing, revealing the presence of a PIK3CA mutation in the patient.<h4>Interventions</h4>The patient's condition was effectively controlled after treatment with PI3K inhibitors.<h4>Outcomes</h4>The patient's progression free survival was prolonged to 7 months after treatment with the PI3K inhibitor. This evidence concerns the gene CDK4 and breast cancer.