Plasma PIK3CA Mutation Testing in Advanced Breast Cancer Patients for Personalized Medicine: A Value Proposition.

Background: Even though endocrine therapy is often initially successful in treating advanced breast cancer, most patients inevitably face disease progression. In advanced hormone receptor-positive (HR+) breast cancer, activation of the PI3K downstream pathway is a critical feature of the mechanism of endocrine resistance. A significant recent advance in treating HR+ advanced breast cancer has been the recent introduction of PI3K inhibitor (PI3Ki) for the treatment of patients with HR+, HER2-negative (HER2-) advanced or metastatic breast cancer that harbors PIK3CA mutations. A value proposition concept was applied to assess the potential benefits of cell-free tumor DNA (ctDNA) testing to identify patients who might respond to PI3Ki treatment.

Content: By applying the framework of the value proposition to >35 publications, in addition to recommendations from professional organizations, it was evident that robust clinical evidence exists to support the role of ctDNA PIK3CA mutation evaluation in identifying patients with advanced breast cancer who could benefit from PI3Ki treatment.

Summary: Detection of PIK3CA gene mutations in HR+HER2- advanced breast cancer patients allows for the identification of patients who might benefit from more effective personalized treatment with molecularly targeted drugs.